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Annals of Oncology Official Journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology editor-in-chief: J.-C. Soria, Villejuif, France associate editors Urogenital tumors G. Attard, Sutton, UK M. De Santis, Birmingham, UK Gastrointestinal tumors D. Arnold, Lisbon, Portugal A. Cervantes, Valencia, Spain J. Tabernero, Barcelona, Spain Breast tumors F. André, Villejuif, France C. Sotiriou, Brussels, Belgium Thoracic tumors T. Mitsudomi, Osaka, Japan J. F. Vansteenkiste, Leuven, Belgium Head and neck tumors A. T. C. Chan, Shatin, Hong Kong E. Cohen, San Diego, California, USA Preclinical and experimental science T. U. E. Helleday, Stockholm, Sweden editors emeriti F. Cavalli, Bellinzona, Switzerland D. J. Kerr, Oxford, UK J. B. Vermorken, Edegem, Belgium Precision medicine C. Swanton, London, UK Gynecological tumors B. Monk, Phoenix, Arizona, USA S. Pignata, Naples, Italy Bioinformatics N. McGranahan, London, UK BioTechnologies E. Mardis, St. Louis, Missouri, USA Melanoma G. Long, Sydney, Australia Onco-Immunology G. Coukos, Lausanne, Switzerland A. Snyder, New York, New York, USA Hematological malignancies K. Tsukasaki, Kashiwa, Japan P. L. Zinzani, Bologna, Italy Supportive care K. Jordan, Halle, Germany Statistics M. Buyse, Brussels, Belgium Epidemiology P. Boffetta, New York, New York, USA Molecular and surgical pathology I.I. Wistuba, Houston, Texas, USA Sarcoma and clinical pharmacology O. Mir, Villejuif, France Annals of oncology online C. Ferté, Villejuif, France Early drug development J.-C. Soria, Villejuif, France Industry corner: perspectives and controversies K. Dhingra, New York, New York, USA R. Govindan, St. Louis, Missouri, USA P. Grimison, Sydney, Australia A. Grothey, Rochester, Minnesota, USA S. Halabi, Durham, North Carolina, USA D. G. Haller, Philadelphia, Pennsylvania, USA K. Hotta, Okayama, Japan R. A. Huddart, Sutton, UK I. Hyodo, Tsukuba, Japan M. Ignatiadis, Brussels, Belgium D. H. Ilson, New York, New York, USA H. Iwata, Aichi, Japan F. Janku, Houston, Texas, USA N. Katsumata, Kawasaki, Japan N. Kiyota, Kobe, Japan C. La Vecchia, Milan, Italy P. N. Jr Lara, Sacramento, California, USA S. Loi, Melbourne, Australia S. Loibl, Neu-Isenburg, Germany F. Lordick, Leipzig, Germany Y. Loriot, Villejuif, France S. Lutzker, San Francisco, California, USA T. Macarulla, Barcelona, Spain M. Martin, Madrid, Spain S. Matsui, Tokyo, Japan J. Maurel, Barcelona, Spain G. McArthur, Melbourne, Australia S. Michiels, Villejuif, France H. Minami, Kobe, Japan Y. Nishimura, Osaka-Sayama, Japan K. Nishio, Osaka-Sayama, Japan M. Ogura, Gifu, Japan A. Ohtsu, Chiba, Japan I. Okamoto, Fukuoka, Japan S. I. Ou, Orange, California, USA X. Paoletti, Paris, France C. Pezaro, Melbourne, Australia P. Pfeiffer, Odense, Denmark S. V. Porceddu, Brisbane, Australia M. R. Posner, New York, USA S. Postel-Vinay, Villejuif, France A. Psyrri, Athens, Greece D. Quinn, Los Angeles, California, USA S. S. Ramalingam, Atlanta, Georgia, USA M. Reck, Grosshansdorf, Germany B. Rini, Cleveland, Ohio, USA R. Rosell, Badalona, Spain A. D. Roth, Geneva, Switzerland R. Salazar, Barcelona, Spain M. Scartozzi, Ancona, Italy N. Schmitz, Hamburg, Germany H.-J. Schmoll, Halle, Germany I. Sekine, Tsukuba, Japan Q. Shi, Rochester, Minnesota, USA A. F. Sobrero, Genoa, Italy G. Sonpavde, Birmingham, Alabama, USA S. Takahashi, Tokyo, Japan M. Toi, Kyoto, Japan B. A. Van Tine, St. Louis, Missouri, USA E. Vilar, Houston, Texas, USA Y.-L. Wu, Guangzhou, China J. C.-H. Yang, Taipei, Taiwan S. Yano, Kanazawa, Japan editorial board M. S. Aapro, Genolier, Switzerland Y. Ando, Nagoya, Japan P. Autier, Lyon, France H. A. Azim Jr, Marseille, France I. Barnes, Oxford, UK J. Baselga, New York, USA J. Bellmunt, Boston, Massachusetts, USA B. Besse, Villejuif, France J. Beyer, Zurich, Switzerland P. Bierman, Omaha, Nebraska, USA C. Bokemeyer, Hamburg, Germany N. Boku, Tokyo, Japan F. Bretz, Basel, Switzerland E. Bria, Verona, Italy E. F. Burgess, Charlotte, North Carolina, USA P. G. Casali, Milan, Italy F. Ciardiello, Naples, Italy A. Comandone, Turin, Italy P. G. Corrie, Cambridge, UK G. Curigliano, Milan, Italy A. Di Leo, Prato, Italy T. Dorff, Los Angeles, California, USA H. Dosaka-Akita, Sapporo, Japan E. A. Eisenhauer, Kingston, Canada A. Eniu, Cluj-Napoca, Romania T. Fenske, Milwaukee, Wisconsin, USA S. Galbraith, Cambridge, UK G. Giamas, Brighton, UK R. Glynne-Jones, Northwood, UK B.-C. Goh, Singapore, Singapore A. Goldhirsch, Milan, Italy executive editor: Lewis Rowett editorial office: Vanessa Marchesi, Paola Minotti Bernasconi, Giovannella Porcu, Annals of Oncology, Via Luigi Taddei 4, CH-6962 Viganello-Lugano, Switzerland R Annals of Oncology is covered in C.A.B. International, Current Clinical Cancer, Current Contents/Clinical MedicineV, Current Contents/Life Sciences, Elsevier BIOBASE/Current Awareness in Biological Sciences, EMBASE/Excerpta Medica, IBIDS, Index Medicus/MEDLINE, The International Monitor in Oncology, Medical Documentation Service, Science Citation IndexV and Science Citation Index Expanded. R subscriptions A subscription to Annals of Oncology comprises 12 issues plus supplements in each volume. Prices include postage, and for subscribers outside the UK delivery is by Standard Air. 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The ultimate responsibility for the use and dosage of drugs mentioned in Annals of Oncology and in the interpretation of published material lies with the medical practitioner. The editors and publisher can accept no liability whatsoever in respect of any claim for damages arising therefrom. Please inform the editors of any errors. notice The content of the abstracts contained in this Abstract Book is subject to an embargo. Abstracts accepted for presentation at ESMO Asia 2016 as Poster Discussion and Poster will be published online on the ESMO website at 16:00 hrs SGT (local Singapore Time) on Wednesday, 07 December 2016. Abstracts accepted for presentation at ESMO Asia 2016 as Proffered Paper (oral presentation) will be published online on the ESMO website at 16:00 hrs SGT (local Singapore Time) on Wednesday, 14 December 2016. Late-breaking abstracts will be made public at the beginning of the official ESMO Asia 2016 Congress session during which they are presented. Abstracts selected for the official ESMO Press Programme will be made public at 00:05 hrs SGT (local Singapore Time) on the day of presentation during the official ESMO Asia 2016 Congress programme. disclaimer No responsibility is assumed by the organisers for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. Because of the rapid advances in medical sciences, we recommend that independent verification of diagnoses and drug dosages should be made. Every effort has been made to faithfully reproduce the abstracts as submitted. However, no responsibility is assumed by the organisers for any omissions or misprints. Annals of Oncology Official Journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology Volume 27, 2016 Supplement 9 ESMO Asia Congress 16–19 December 2016, Singapore ABSTRACT BOOK Guest Editors: ESMO Asia 2016 Scientific Committee Annals of Oncology Official Journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology Volume 27, 2016 Supplement 9 Abstract Book of ESMO Asia Congress Singapore, 16–19 December 2016 About ESMO ESMO Asia 2016 Officers and Scientific Committee ESMO Asia Congress 2016 Organisation Acknowledgements ix-v ix-vi ix-vii ix-viii Abstracts Basic science Biomarkers Breast cancer, early stage Breast cancer, locally advanced Breast cancer, metastatic CNS tumours Developmental therapeutics Endocrine tumours Gastrointestinal tumours, colorectal Gastrointestinal tumours, non-colorectal Genitourinary tumours, non-prostate Genitourinary tumours, prostate Gynaecological cancers Haematological malignancies ix1 ix9 ix19 ix30 ix35 ix42 ix46 ix52 ix53 ix68 ix86 ix90 ix94 ix104 Head and neck cancer Immunotherapy of cancer Melanoma and other skin tumours Neuroendocrine tumours New diagnostics NSCLC, early stage NSCLC, locally advanced NSCLC, metastatic Palliative care Psycho-oncology Sarcoma SCLC Supportive care Thoracic malignancies, other Translational research Tumour biology and pathology General interest Late-breaking abstracts Drug index Translational Research index Note: Abstract suffixes “O” indicates a submitted abstract accepted for Proffered Paper (oral) presentation “PD” indicates a submitted abstract accepted for Poster Discussion “P” indicates a submitted abstract accepted for Poster Presentation “TiP” indicates a submitted abstract accepted for Poster Presentation, Trial in Progress __PR indicates a submitted abstract selected for inclusion in the ESMO Press Programme Volume 27 | Supplement 9 | December 2016 ix112 ix123 ix126 ix130 ix132 ix134 ix136 ix139 ix157 ix161 ix163 ix169 ix170 ix177 ix179 ix181 ix184 ix190 ix192 ix194 The European Society for Medical Oncology (ESMO) ESMO is the leading professional organisation for medical oncology, with the overarching goal of improving outcomes for cancer patients everywhere. We are the society of reference for oncology education and information, and are committed to supporting our members to develop and advance in a fast-evolving professional environment. Founded in 1975, ESMO has European roots with a global reach: we welcome oncology professionals from around the world. We are a home for all oncology stakeholders, connecting professionals with diverse expertise and experience, and speaking with one voice for our discipline. Our education and information resources support an integrated multi-professional approach to cancer care, from a medical oncology perspective. We seek to erase boundaries in cancer care, whether between countries or specialities, and pursue our mission across oncology, worldwide. The ESMO community brings together over 14,000 oncology professionals from over 130 countries. Drawing on 40 years of experience and around 500 expert committee members, ESMO serves its members and the oncology community through: • • • • • Post-graduate oncology education and training Career development and leadership training for the next generations of oncologists International congresses and workshops to share expertise and best practice, learn about the most up-to-date scientific advances, and connect with colleagues in related disciplines. Continuously reviewed, evidence-based standards for cancer care in Europe Advocacy and consultation to foster a favourable environment for scientific research Cancer care is rapidly becoming more integrated and more specialised; whether their field is research, diagnosis, treatment, care, or advocacy, oncology professionals need to both build their specialist knowledge and connect with the best practitioners in other disciplines worldwide. ESMO membership makes this possible. Please visit esmo.org to learn more. Across Oncology. Worldwide. ESMO Executive Board 2016 President President-Elect Past President and Membership Committee Chair Treasurer Educational Committee Chair National Representatives and Membership Committee Chair EU Policy Committee Chair Global Policy Committee Chair Guidelines Working Group Chair Press and Media Affairs Committee Chair Practising Oncologists Committee Chair Board Member Board Member Board Member Board Member Fortunato Ciardiello, Naples, Italy Josep Tabernero, Barcelona, Spain Rolf A. Stahel, Zurich, Switzerland Emile Voest, Amsterdam, The Netherlands Andrés Cervantes, Valencia, Spain Fatima Cardoso, Lisbon, Portugal Paolo G. Casali, Milan, Italy Alexandru Eniu, Cluj-Napoca, Romania George Pentheroudakis, Ioannina, Greece Solange Peters, Lausanne, Switzerland Stefan Rauh, Luxembourg Dirk Arnold, Lisbon, Portugal Alexander M. M. Eggermont, Villejuif, France Jacek Jassem, Gdansk, Poland Christoph Zielinski, Vienna, Austria ESMO Asia 2016 Officers ESMO and Congress President Fortunato Ciardiello, Naples, Italy Scientific Committee Chair Rolf A. Stahel, Zurich, Switzerland Scientific Co-Chair Hyun Cheol Chung, Seoul, Republic of Korea Educational Chair Andrés Cervantes, Valencia, Spain Educational Co-Chair Yi-Long Wu, Guangzhou, China Local Officer Ravindran Kanesvaran, Singapore Press Officer Solange Peters, Lausanne, Switzerland Scientific Committee Basic science and translational research Chair: Richard Marais, Manchester, UK Anton Berns, Amsterdam, Netherlands David Huang, Melbourne, Australia Seock-Ah Im, Seoul, Republic of Korea Hitoshi Nakagama, Tokyo, Japan Ruth Palmer, Gothenburg, Sweden Joan Seoane, Barcelona, Spain Sheila Singh, Hamilton, ON, Canada Britta Weigelt, New York, NY, USA Breast cancer Chair: Rebecca Dent, Singapore Fabrice André, Villejuif, France Fatima Cardoso, Lisbon, Portugal Sung Bae Kim, Seoul, Republic of Korea Sherene Loi, Melbourne, Australia CNS tumours Chair: Martin Taphoorn, Amsterdam, Netherlands Alba Brandes, Bologna, Italy Rakesh Jalali, Mumbai, India Ryo Nishikawa, Saitama, Japan Michael Weller, Zurich, Switzerland Developmental therapeutics Chair: Jean-Pierre Delord, Toulouse, France Gastrointestinal tumours Chair: Dirk Arnold, Lisbon, Portugal Ian Chau, Sutton, UK Tae Won Kim, Seoul, Republic of Korea Florian Lordick, Leipzig, Germany Atsushi Ohtsu, Kashiwa, Japan Timothy Price, Adelaide, Australia Eric Van Cutsem, Leuven, Belgium Genitourinary tumours Chair: Sun Young Rha, Seoul, Republic of Korea Gynaecological cancers Chair: Michael Friedlander, Sydney, Australia David Bowtell, Melbourne, Australia Keiichi Fujiwara, Saitama, Japan Jonathan Ledermann, London, UK Cristiana Sessa, Bellinzona, Switzerland David SP Tan, Singapore Haematological malignancies Chair: Zhi-Ming Li, Guangzhou, China Head and neck cancer Chair: Lisa Licitra, Milan, Italy Anthony T.C. Chan, Hong Kong, China Anil D’Cruz, Mumbai, India Vincent Grégoire, Brussels, Belgium Hisham Mehanna, Birmingham, UK Amanda Psyrri, Athens, Greece Makoto Tahara, Tokyo, Japan Immunotherapy of cancer Chair: John Haanen, Amsterdam, Netherlands Daniel Tan, Singapore Jin Li, Shanghai, China Lilian Siu, Toronto, ON, Canada Violetta Serra, Barcelona, Spain Olivier Rixe, Albuquerque, NM, USA Joaquim Bellmunt, Boston, MA, USA Bernard Escudier, Villejuif, France Ian Davis, Melbourne, Australia Daniel Y.C. Heng, Calgary, AL, Canada Ravindran Kanesvaran, Singapore Bin Tean Teh, Singapore Christian Buske, Ulm, Germany Won Seog Kim, Seoul, Republic of Korea Yok-Lam Kwong, Hong Kong, China Owen A. O’Connor, New York, NY, USA Hui-Lai Zhang, Tianjin, China Yutaka Kawakami, Tokyo, Japan Tony S.K. Mok, Hong Kong, China Han Chong Toh, Singapore Melanoma and other skin tumours Chair: Grant McArthur, Melbourne, Australia Jun Guo, Beijing, China Georgina Long, Sydney, Australia Paul Lorigan, Manchester, UK Caroline Robert, Villejuif, France Sarcoma Chair: Akira Kawai, Tokyo, Japan Supportive & palliative care Chair: Kazuo Tamura, Fukuoka, Japan Matti Aapro, Genolier, Switzerland Alexandre Chan, Singapore Karin Jordan, Halle, Germany Yeur-Hur Lai, Taipei, Taiwan Ian Olver, Sydney, Australia Thoracic cancers Chair: Caicun Zhou, Shanghai, China Myung Ju Ahn, Seoul, Republic of Korea Dirk De Ruysscher, Maastricht, Netherlands Keunchil Park, Seoul, Republic of Korea Gregory J. Riely, New York, NY, USA Egbert Smit, Amsterdam, Netherlands Qing Zhou, Guangzhou, China Jean-Yves Blay, Lyon, France Paolo G. Casali, Milan, Italy Dae Geun Jeon, Seoul, Republic of Korea Robin Jones, London, UK Roger Ngan, Hong Kong, China Richard Quek, Singapore Edward Wang, Manila, Philippines The European Society for Medical Oncology wishes to express its appreciation and gratitude to all of the above experts for their major effort to select the content of this Abstract Book. ESMO Asia Congress 2016 Organisation Organisation ESMO Head Office Via Luigi Taddei 4 CH-6962 Viganello-Lugano Switzerland Tel. Fax E-mail Accommodation MCI Group Asia Pacific PCO Consultant Singapore Tel. Fax E-mail Venue +41 (0)91 973 19 94 +41 (0)91 973 19 18 [email protected] www.esmo.org +65 6411 6687 +65 6496 5599 [email protected] www.mci-group.com Suntec Singapore International Convention & Exhibition Centre 1 Raffles Boulevard Suntec City Singapore Tel. Fax +65 6337 2888 +65 6825 2222 www.suntecsingapore.com Annals of Oncology 27 (Supplement 9): ix1–ix8, 2016 doi:10.1093/annonc/mdw573 1PD Breast cancer blood-derived exosomes: Characterisation of protein composition in search for new biomarkers O.S. Tutanov1, S.N. Tamkovich1, A. Grigoryeva2, E. Ryabchikova2, T. Duzhak3, Y. Tsentalovich3, P. Laktionov1, V. Vlassov1 1 Laboratory of Molecular Medicine, Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russian Federation, 2Group of Microscopy, Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russian Federation, 3Group of Proteomics and Metabolomics, International Tomography Center SB RAS, Novosibirsk, Russian Federation Background: Exosomes are known to be involved in the signalling processes and cellto-cell communication both in healthy organisms and during the development of various cancer types. However, the exact mechanisms of sorting and secreting as well as the circulation patterns and composition of exosomes are still unclear. The aim of our research is to identify protein content of blood-derived exosomes and determine potential biomarkers specific for breast cancer development. Since exosomes are naturally binding with the cells, we decided to extract them not only from blood plasma but also from blood cells surface in order to understand their percentage, properties and composition. Methods: Exosomes from blood plasma and blood cell surface-bound exosomes were obtained using methods developed in our lab (RF Patent #2556825, #2571507). The resultant samples were characterized by transmission electron microscopy (TEM) and immunogold labeling to state the presence of characteristic exosome tetraspanins CD-9, CD-24 and CD-63. Proteins from exosome samples were separated by electrophoresis in gradient polyacrylamide gel and identified by MALDI-TOF analysis. Results: Immunogold labeling confirmed the presence of antigens characteristic for exosomes: CD-9, CD-24 and CD-63. The evaluation of particle diameter of 14 950 exosomes has shown that the blood of breast cancer patients is mostly presented with exosomes diameter from 50 to 70 nm, the blood of healthy women - from 30 to 50 nm. We discovered that 61% of blood-derived exosomes are bound to the surface of blood cells. MALDI TOF/TOF identified more than 150 proteins in exosomes from the blood of healthy women (n ¼ 5) and breast cancer patients (n ¼ 5), the majority of which are found in exosomes for the first time (according Exocarta database at the summer of 2016). Conclusions: Although it is still unclear what leads to differences in exosome size in plasma and on the surface of the blood cells the results suggest the importance of this exosome fraction and provides us with the new perspective in exosome research. Further analysis with expanded sample size may lead us to biomarker patterns as well as new insight into exosome structure. Legal entity responsible for the study: Laboratory of Molecular Medicine, Institute of Chemical Biology and Fundamental Medicine of Siberian Branch of Russian Academy of Sciences Funding: Russian Foundation for Fundamental Research grant Disclosure: All authors have declared no conflicts of interest. 2P Novel cKIT kinase inhibitor, BPRCKJ001, as an advanced therapeutic candidate for GIST H-Y. Shiao1, H-J. Tsai2, W-H. Lin1, T-A. Tsu1, T-K. Yeh1, C-T. Chen1, W-T. Jiaang1 1 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan, 2National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan Background: During the past decade, first-line use of imatinib has benefited GIST patients. GIST patients develop imatinib-resistance due to secondary mutation in cKIT after 20-24 months of drug treatment. Although the 2nd line drugs such as, sunitinib is effective, activation loop mutations quickly overcame their potent inhibitory effects. Moreover, these drugs have numerous potential side-effects. Even with the newly launched sorafenib and nilotinib for advanced GIST, the long term clinical outcome was still not very promising for GIST patients, due to the rapid development of drug resistance on cKIT. Methods: IBPR has identified a series of novel cKIT inhibitors, the BPRCKJ series, which exhibited potent cKIT kinase activity inhibition. To evaluate the potential of BPRCKJ compounds as novel cKIT inhibitors against GIST, eight different imatinibresistant mutated cKITs were selected to examine the inhibitory activities of BPRCKJ series. The results showed that BPRCKJ series has a broad spectrum activity against various forms of imatinib-resistant mutant c-KITs. Most importantly, the ability to overcome imatinib- and sunitinib-resistant mutant cKITs is demonstrated. Results: Through the comprehensive SAR study, we had identified BPRCKJ001 as a potential candidate, which was shown to strongly inhibit the enzymatic activities of several mutant c-KIT. BPRCKJ001 also effectively inhibited three GIST sensitive and resistant cell lines with IC50 values below 20 nM. It is interesting to note that BPRCKJ001 is 10-times and 400-times more potent than sunitinib in GIST430 cells and sunitinib-resistant cell lines (GIST48), respectively. The Western blot analyses also clearly showed that BPRCKJ001 can suppress the cKIT phosphorylation and downstream AKT phosphorylation more effectively than imatinib and sunitinib in GIST430 cells. Conclusions: BPRCKJ001 had shown excellent in vitro effects, targeting against both imatinib- and sunitinib-resistant mutants in both enzymatic and cellular systems. More importantly, BPRCKJ001 also demonstrated in vivo efficacy by oral administration in GIST430 xenograft model. These results indicate that CKJBPR001 series has reasonable pharmaceutical properties to be developed as a potential cKIT inhibitor Legal entity responsible for the study: Weir-Torn Jiaang Funding: MOEA, Taiwan Disclosure: All authors have declared no conflicts of interest. 3P Anti-VEGF and integrin-linked kinase knockdown inhibit angiogenesis in vitro and suppress vascular tumor growth in vivo P. Mabeta Physiology, University of Pretoria, Pretoria, South Africa Background: Angiogenesis is the process by which new blood vessels are formed. It is also a key feature in the growth and progression of several cancers. Studies have identified vascular endothelial factor (VEGF) as an important regulator of angiogenesis in both the physiological and pathological settings. In the context of cancer, VEGF signalling was shown to be impaired in several neoplasms. This discovery led to the development of therapies against VEGF. While antiangiogenic VEGF-targeted therapy has resulted in increased cancer patient survival, the development of resistance has necessitated the discovery of alternative or complimentary therapeutic strategies. Integrin-linked kinase (ILK) is an effector of integrin-mediated cell adhesion. It is also involved in the regulation of the PI3k/Akt pathway. Methods: The effects of ILK knockdown and anti-VEGF were evaluated on endothelial cell proliferation using BRdU-labeling, and on migration and invasion using the xcelligence system. The effects of the combination treatment on vascular tumour growth were studied in C57BL/6 mice inoculated with sEnd.2 cells. The secretion of VEGF, platelet derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) were measured employing ELISA. Results: ILK knockdown with siRNA and anti-VEGF treatment with DMH4 resulted in a more pronounced decrease in cell survival, proliferation and migration when compared to the individual treatments, even following VEGF induction. The combination treatment was also more potent in inhibiting angiogenesis in vitro. Western blot analysis revealed the suppression of Akt phosphorylation. Also, results revealed a decrease in the expression of HIF1-a and nitric oxide (NO), as well as a decrease in proangiogenic factors, namely, VEGF, PDGF and bFGF. In vivo, there was a significant reduction in tumor diameter in vascular tumor-bearing mice treated with Cpd 22, an inhibitor of ILK and DMH4 (n ¼ 6 per group; P < 0.05). Immunohistochemical evaluation revealed a reduction in microvessel density in treated mice. Conclusions: Therefore, the combination approach may be useful in the elaboration of antiangiogenic therapy in vascular tumors, further studies are warranted. Legal entity responsible for the study: Peace Mabeta Funding: National Research Foundation; University of Pretoria Disclosure: All authors have declared no conflicts of interest. C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts Basic science abstracts 4P Annals of Oncology IGF-IR, but not EGFR, regulates DNA damage response in HeLa cells following irradiation M. Nishagowri, A. Kaida, M. Miura Oral Radiation Oncology, Tokyo Medical and Dental University, Tokyo, Japan 6P Quinazoline clubbed s-triazine derivatives as VEGFR2 kinase inhibitor: Design, synthesis, docking, antiproliferative and antiangiogenic activity on cancer-induced chick embryo A. Verma1, P. Pathak1, P.K. Shukla1, V. Kumar1, A. Kumar2, A.K. Singh3 Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences (SHIATS), Allahabad, India, 2Pharmaceutical Sciences, S. V. Subharti University, Meerut, India, 3Clinical, ESIC, Delhi, India 1 Background: The roles of receptor tyrosine kinases in DNA damage response (DDR) are still largely unknown. In this study, we examined the possible involvement of insulin-like growth factor I receptor (IGF-IR) and epidermal growth factor receptor (EGFR) in the DNA damage response (DDR) following irradiation. Methods: HeLa cells expressing the fluorescence ubiquitination-based cell cycle indicator (Fucci) probes (HeLa-Fucci cells) were used in this study. Kinetics of the Fucci fluorescence were detected by FACS and time-lapse imaging. NVP-AEW541, Tyrphostin AG1478, LY294002, PD98059, NU7026 were used as specific inhibitors for IGF-IR, EGFR, PI3-K, MEK, and DNA-PKcs, respectively. Phosphorylation of ERK1/2 and Akt was detected by western blotting. Double strand breaks (DSBs) were detected by immunofluorescence staining for 53BP1. Cells were irradiated using an RX-650 Cabinet X-radiator system (Faxitron). Results: To investigate the possible involvement of EGFR and IGF-IR in G2 arrest, FACS analysis and time-lapse imaging of Fucci fluorescence were performed using specific inhibitors. Results showed that inhibition of IGF-IR, but not that of EGFR, prolonged G2 arrest, which was irrespective of cell cycle phases at irradiation, i.e., red (G1 phase) or green (S/G2 phases) phase in the Fucci system. Similarly, only inhibition of IGF-IR decreased the DSB repair activity. Hereafter, further analysis was focused on IGF-IR-associated events. We next attempted to identify the responsible IGF-IRdownstream signaling pathways. Irradiation phosphorylated both Akt and ERK; however, inhibition of IGF-IR abrogated activation of only Akt. Moreover, inhibition of PI3-K/Akt, but not that of MEK/ERK, prolonged G2 arrest, which mimicked that of IGF-IR. Inhibition of DNA-PKcs, a major factor of non-homologous end joining (NHEJ), also prolonged G2 arrest. Conclusions: We conclude that irradiation is likely to preferentially activate the IGFIR/PI3-K/Akt signaling pathway in HeLa-Fucci cells, which may enhance DSB repair, eventually contributing to reduction of G2 arrest in the DDR following irradiation. Legal entity responsible for the study: Tokyo Medical and Dental University Funding: Tokyo Medical and Dental University, MEXT Japan Disclosure: All authors have declared no conflicts of interest. 5P Background: Angiogenesis is a fundamental and complex process of endothelial cells, pericytes and responsible for executing normal physiological responses like wound healing, embryonic development and bone remodelling etc. Judah Folkman and colleagues established the concept of angiogenic inhibition in tumour growth. The epidermal growth factor (EGF) receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways play an important role in the growth, metastatic potential of tumours and their inhibition is a prime target for various therapeutic agents including quinazoline based compounds because it represents the most validated signalling pathway. Considering that we have developed quinazoline clubbed 1,3,5-s-triazine derivatives (QCTD) as a potential inhibitor of VEGFR2 kinase for anti-cancer activity. Methods: Designing of (QCTD) was done on the basis of molecular field mapping and alignment studies with standard angiogenic inhibitor vandetanib. Further docking studies were performed by Autodock 4.2 for most promising similar designed derivatives and all screened (QCTD) were developed via cost-effective synthetic route. The synthesized derivatives were evaluated for their in-vitro anti-cancer activity on four different cell line HeLa (Human Cervical Carcinoma), MCF-7 (Breast Carcinoma), HL60 (Human promyelocytic leukemia) and HepG2 (Human Hepatocellular carcinoma) and and also in-ovo angiogenic inhibition was performed on chick embryo. Results: All the designed derivatives explored more than 50% similar pattern of field and atomic arrangement. Thiourea (8b), chloranilino(8d), hrdrazicarboxamide(8j) and methylamino(8m) substituted derivatives selected for docking calculations due to higher similarity value. Docking studies revealed significant result like standard drug vandetanib on protein VEGFR2 kinase (PDB ID: 3EWH). IC50 report clearly marked that derivatives have significant antiproliferative action against wide verity of cancer cell line and in-ovo result explored that derivatives are non-toxic to the normal cells. Conclusions: We have developed a novel class of anticancer agents. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. Targeted degradation of anaplastic lymphoma kinase by target degraducer in non-small cell lung cancer 7P J.Y. Hwang, C-H. Park, D.H. Lee, C.H. Kang, C.O. Lee, J.D. Ha Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea Selenium-enriched polysacchride green tea extract alters the early stage hepatocellular carcinoma by angiogenesis hypoxia and metastatic inhibition V. Kumar1, P.C. Bhatt2, F. Anwar3, A. Verma1 Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences (SHIATS), Allahabad, India, 2Pharmacy, Jamia hamdard, New Delhi, India, 3Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia 1 Background: Recently, a new and powerful technology, called “proteolysis targeting chimeras” (PROTAC), has been highlighted in the drug discovery area. Treatment of PROTAC molecule, which contains a ligand for the targeted protein, a ligand for E3 ubiquitin ligase binding, and a linker for connection of two ligands, successfully induced targeted protein degradation, thereby inhibiting cancer growth in in vivo animal model study. Anaplastic lymphoma kinase (ALK) gene fused to various partner genes are observed in 3–7% of non-small cell lung cancer (NSCLC) in humans. The constitutively activated ALK fusions play an essential role in cancer growth and survival. In this study we aimed to identify novel ALK target degraders (TDs) by applying PROTAC technology. Methods: LDK-378 (ceritinib) as an ALK ligand and VHL or CRBN as an E3 ubiquitin ligase were selected. Hydroxyproline analogs (HP-7) and pomalidomide were used for VHL and CRBN E3 ligase ligands, respectively. All TDs were evaluated in enzymaticand cell-based assays. ALK degradation by TDs were confirmed by western blotting in SU-DHL-1 cell lines. In vivo antitumor activities were evaluated in xenograft mouse model with H3122 cell lines. Results: A series of TDs were synthesized with various linkers. The TDs showed antiALK activities in both enzymatic and cell-based assays. The TDs exhibited ALK degradation through ubiquitination-proteasome process in cells. Finally, the TDs could inhibit tumor growth in xenograft study with H3122 cells. Conclusions: These results suggest that the ALK-TDs, inducing ALK degradation, represents a promising strategy for the treatment of ALK-driven NSCLC. Legal entity responsible for the study: Jong Yeon Hwang Funding: Korea Research Institute of Chemical Technology Disclosure: All authors have declared no conflicts of interest. ix2 | abstracts Background: Targeting various pathways during progression and expansion of hepatocellular carcinoma (HCC) is one promising strategy to control the complications of liver cancer. The present investigation targeted the potential effect of seleniumenriched green tea polysaccharides on HOX, hypoxia-induced factor, Vascular Endothelium Growth Factor (VEGF), matrix metalloproteinase (MMP-2 and MMP-9), alpha fetoprotein (ALF) and CD31 in diethylnitrosamine induced HCC rats. Methods: The extract was rich in uronic acid (3.2%), carbohydrate (91.2%) and 4.5 lg/g of selenium to represent SCP. This extract was evaluated for apoptosis mechanism against HCC cell lines viz., Hep-G2 and HuH-7. Invivo study, can be read as: Normal; NC þ SCP (20 mg/kg); DEN treated; DEN þ SCP (20 mg/kg). The treatment was initiated a week before the DEN administration and was carried for 22 weeks. HCC via DEN is known for significant alteration in biochemical, inflammatory, antioxidant parameters and liver histopathology. Furthermore we also estimated the HOX, HIF, VEGF, MMP-2 and MMP-9, ALF and CD31 parameters. Results: In vitro studies confirmed the inhibition of the growth of Hep-G2 and HuH-7 cells in a dose-dependent manner via scavenging the cell at G2 phase of cells. Cell death was confirmed via enhanced caspase 3, 9 activity and Bax/Bcl2 ratio, suggesting the effect on the c-caspase pathway on apoptosis. The animal studies confirm the alteration in biochemical, antioxidant and inflammatory markers. Further to substantiate our claim SCP also inhibited the protein elevation of HIF-1a, VEGF, MMP-2, 9 and CD31 compared with DEN control group rats. The alteration in these parameters was sufficient to confirm the reduction of angiogenesis, hypoxia and metastasis and proved the potential effect of SCP at early expansion stage of disease. Conclusions: Collectively, we can conclude that selenium-enriched polysaccharides of green tea reduced the progression and expansion of hepatocellular carcinoma via multiple mechanisms. Legal entity responsible for the study: N/A Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology Funding: SHIATS Disclosure: All authors have declared no conflicts of interest. 8P Cdk4/6 inhibitor activity in metastatic bladder cancer cell lines is independently of RB1 status pez-Caldero n2, C. Segovia3, M. Duen ~as3, D. Castellano1, C. Rubio2, F. Lo ndez3, I. Otero2, R. Manneh4, G. De Velasco4, J. Paramio2 M. Martinez-Ferna 1 Medical Oncology; Cell and Molecular Oncology Group, University Hosptial 12 De Octubre, Madrid, Spain, 2Cell and Molecular Oncology Group, University Hosptial 12 De Octubre, Madrid, Spain, 3Cell and Molecular Oncology Group; Molecular Oncology Unit, CIEMAT, University Hosptial 12 De Octubre, Madrid, Spain, 4Medical Oncology, University Hosptial 12 De Octubre, Madrid, Spain Background: Metastatic bladder cancer is treated, in most cases, by cystectomy and platinum-based chemotherapy. Various targeted therapies are being clinically and preclinically tested for bladder cancer management. Metastatic bladder cancer has been associated with loss of cell cycle control. TCGA analysis also revealed that TP53 mutations were mutually exclusive in their relationship with overexpression and amplification of MDM2, thereby resulting in inactivation of p53 function in 76% of samples. Defects in the RB pathway are another major mechanisms by which cell cycle control is lost in metastatic bladder cancer. The CDK 4/6 complex combines with cyclin D1 to inhibit RB activity. Therapeutic targeting of this complex improves outcome in ER positive advanced breast cancer. Methods: Palbociclib (PD-0332991) is a cdk4/6 inhibitor currently tested for the treatment of other malignancies characterized by the presence of a functional RB1 gene. A series of bladder cancer cell lines of known genomic characteristics and differing in their RB1 status, were tested for their sensitivity to palbociclib. Results: Unexpectedly, we observed a similar response to palbociclib in pRb wt and pRb mutant cell lines in vitro and in xenografts in vivo, although with different biochemical and cell cycle effects. Genomic characterization of these treated cells shows strong gene expression divergence as a consequence of palbociclib treatment in pRb wt and mutant cells. Nonetheless, bioinformatic analyses revealed FoxM1 as a possible common regulator of some downregulated genes in both cases. Importantly, FoxM1 has been demonstrated a bona fide cdk4 substrate and may confer cis-platinum resistance. We observed reduced FoxM1 phosphorylation upon palbociclib treatment in all cell lines tested, and also increased sensitivity to cis-platinum. Remarkably, we found that phosphorylated FoxM1 is a potential poor prognosis factor in human bladder cancer clinical samples. Conclusions: in our study we observed that the activity of palbociclib in bladder cancer cell lines described is indepedently of the RB1 status and showed synergistic activity with cisplatin. Future studies, using mouse models based on the genetic inactivation of Rb1 with other tumor suppressor genes, will precede the possible development of appropriate clinical trials testing the use of palbociclib in the management of bladder cancer patients. Legal entity responsible for the study: N/A Funding: I þ 12 Research Institute Disclosure: All authors have declared no conflicts of interest. 9P reduction in 50 lM compared with control cases (p < 0.05 and p < 0.001, respectively). € › According to the administration time and frequency of GO6983, the metastatic lung nodules showed 80% of reduction (p < 0.001) in the three times pre-treatment group, but in the post-treatment group there was no significant difference. fi According to the administration dose of mouse melanoma cell lines, there was 44% improvement of survival days in the group at the dose of 2.5 x 104 cell line with continuous treatment of € GO6983 compared with control group. However, there was no significant difference in the survival days as gradual increasing the dose of the melanoma cell lines. € Conclusions: In conclusion, treatment of GO6983 to the NK cell showed activation of NCR1, 2, and 3 that might mean indirect activation of NK cells. Moreover, induction of activated NK cells in the pretreatment group resulted in significant anti-metastatic effect and improved survival. Legal entity responsible for the study: HY Kim Funding: N/A Disclosure: All authors have declared no conflicts of interest. 10P N. Gharaee, M. Habibpour, H. Sepehri, L. Delphi Biology, Tehran University, Tehran, Iran Background: Tumor treating fields (TTFs) are alternating fields with low intensity and intermediate frequency, that are used as a novel treatment for cancer therapy. TTFields lead to disruption in mitotic process and inhibit the proliferation of cancer cells. In the present study the effect of TTF therapy in cellular model of breast cancer is investigated. For this goal TTFields alone and in combination with doxorubicin as a chemical drug were examined. Methods: MDA-MB-231 human breast cancer cells was exposed to TTFields for a duration of 30hours.TTFields also applied when cells were treated with doxorubicin in IC10 dose. The cells proliferation ratio was assessed after 72h. Results: Treatment with tumor treating fields inhibits the proliferation of cancer cells significantly. The optimal frequency that caused the most inhibitory effect was determined to be 150kHz. Combination of TTF therapy with using of optimal frequency and treatment with doxorubicin in IC10 dose led to further decrease in proliferation, compared to TTF therapy alone. Moreover, the sensitivity to chemotherapeutic agent was increased by the aid of TTFields. Conclusions: These findings demonstrated that TTFields contain efficiency to arrest cancer cells proliferation. These results also show that TTFields can support chemical drug efficiency. Our studies indicate that, using TTF co-administrated with doxorubicin can be used as an alternative strategy for cancer therapy in breast cancer cases to improve the effects of the drugs and increase the sensitivity of cancer cells. Legal entity responsible for the study: Ministry of Science, Research and Technology Tehran University Funding: Biology Department of Tehran University Disclosure: All authors have declared no conflicts of interest. 11P Anti-tumor effects mediated by the activation of natural cytotoxicity receptors of natural killer cells H.Y. Kim1, K.H. Lee2, J.S. Song3, K.Y. Shim4, J.I. Lee4 Hematooncology, Internal Medicine, Hallym University Medical Center, Anyang, Republic of Korea, 2Microbiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea, 3Pathology, Catholic Kwandong University International St. Mary’s Hospital, Incheon Metropolitan City, Republic of Korea, 4 Hematooncology, Internal Medicine, Yonsei University Wonju Severance Christian Hospital, Wonju, Republic of Korea Efficacy of tumor treating field therapy alone and in combination with doxorubicin in cellular model of breast cancer Hypomagnesaemia in the context of cetuximab/panitumumab and proton pump inhibitor therapy R. Joshi1, P. Connolly2, T. Foo2, J. Rowe2 Medical Oncology, Elizabeth Vale, Lyell McEwin Hospital, Adelaide, Australia, 2 Medical Oncology, Lyell McEwin Hospital, Adelaide, Australia 1 1 Background: The natural killer cell (NK cell) is very important for the removal of cancer cells in the stage of tumor growth and metastasis as well as in the early stage of the biologic immune system. The tumor killing system of NK cell can be induced by antibody-dependent cell-mediated cytotoxicity (ADCC) and natural cytotoxicity receptors (NCR)-mediated natural killing mechanism. Methods: In this study, the anti-cancer effect of NK cells through the promotion of cytotoxicity was demonstrated in the experiment of human hepatocellular carcinoma € cell lines, HepG2 and Hep3B using GO6983, a molecular substance to induce NCR expression of NK cells. A lung metastasis mouse model was made in C57BL/6 mouse aged 8 weeks with a mouse malignant melanoma cell line, B16BL6. Results: The results are as follows. 1) The expression of NCR1, 2, and 3 with the € treatment of GO6983 increased 4.11, 57.34 and 9.89 times, respectively compared with € those without treatment. 2) The cytotoxicity of NK cells with the treatment of GO6983 showed destruction of 22.3% in Hep3B and 21.6% in HepG2 compared with 10% in control cases. 3) In lung metastasis mouse model, ‹ Activated NK cells revealed 43.2% reduction of metastastic lung nodules in cases treated with the dose of 10lM and 51.2% Background: The epidermal growth factor inhibitors cetuximab and panitumumab are associated with hypomagnesaemia. Proton pump inhibitors (PPIs) also have a similar association. The aim of our study was to determine whether patients on both classes of agents develop more significant levels of hypomagnesaemia; which might have potential therapeutic implications. Methods: This study was performed as a retrospective cohort analysis. Fifty consecutive patients treated with cetuximab or panitumumab were selected from our oncology database. Their medical records were reviewed to determine: if they were receiving PPI therapy or other agents contributing to hypomagnesaemia, if they received magnesium supplementation, and the presence of depressive illness. Magnesium levels before, during and after treatment were recorded. Linear mixed-effects models and logistic generalised estimating equation (GEE) models were used for statistical analysis. Unstructured covariance structure was used within the linear mixed-effects model as it resulted in the model of best-fit. Results: Cetuximab and panitumumab were associated with significant reductions in serum magnesium levels (p < 0.0001). Levels dropped by a mean of 0.24 (95% confidence intervals [CI]: -0.29, -0.18[RJ1]) during treatment. After completion of treatment, levels returned to within normal limits, with a mean increase of 0.22 (95% CI: 0.16, 0.27[RJ2]) . There was no correlation between concurrent PPI therapy and increased severity of hypomagnesaemia. Of note, there was a positive relationship Volume 27 | Supplement 9 | December 2016 doi:10.1093/annonc/mdw573 | ix3 abstracts between depression and hypomagnesaemia (global p value ¼ 0.0240). For every one unit increase in magnesium level[RJ3] there was an 85% reduction in the rate of depression (odds ratio ¼ 0.15, 95% CI: 0.03, 0.78[RJ4]) . Conclusions: EGFR inhibitor therapy is associated with hypomagnesaemia. There was a correlation between depression and low magnesium levels. Further investigation is warranted to evaluate the links between these medical conditions, and the role of PPI therapy and magnesium supplementation. Legal entity responsible for the study: South Australia Department of Health Funding: N/A Disclosure: All authors have declared no conflicts of interest. 12P Individualized breast cancer therapy using Mcl-1 inhibition based combination M.H. Bashari1, S. Malvestiti2, F. Fan2, S. Vallet2, M.H. Cardone3, J.T. Opferman4, D. J€ager2, K. Podar2 1 Pharmacology and Therapy, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia, 2Medical Oncology, National Center for Tumor Diseases/ University Hospital Heidelberg, Heidelberg, Germany, 3Eutropics Pharmaceuticals, Inc, Cambridge, MA, USA, 4Cell & Molecular Biology Department, St. Jude Children’s Research Hospital, Memphis, USA Background: Breast cancer (BC) is leading cause of cancer-related mortality in women. Anti-apoptotic Bcl-2 family members including Bcl-2, Bcl-xL and myeloid cell leukemia-1 (Mcl-1) control the intrinsic pathway of apoptosis. Elevated Mcl-1 levels have been correlated with poor prognosis. The aim of this study is to evaluate a rationally-derived combination of Mcl-1-inhibitor with Bcl-2 or Bcl-xL inhibitors as well as with conventional BC treatment and to provide the derived rationale to therapeutically target Mcl-1. Methods: The anti-BC cell-activity of the novel small molecule Mcl-1 inhibitor EU5346 was evaluated alone or in combination with other antiapoptotic agents, hormone therapy, targeted therapy, or chemotherapy using proliferation and spheroid forming assays as well as immunoblotting in different BC cell lines. Synergistic activity of combination therapies was determined by the Chou-Talalay method. Results: Using protein profiling Mcl-1 is consistently overexpressed in all BC subtypes while Bcl-2 and Bcl-xL are variably expressed. We then performed selective treatments with Mcl-1/Bcl-2/Bcl-xL inhibitors. As expected, cell proliferation was significantly reduced in correspondence to the protein levels of antiapoptotic Bcl-2 family member, thereby indicating the rational combination of Mcl-1 inhibitor with Bcl-2/Bcl-xL inhibitors. Importantly, Bak, Bim and Noxa protein levels predict the IC50 of EU-5346 in all BC subtypes. We then demonstrated that a protein level-based drug combination Mcl-1 inhibitor with Bcl-2/Bcl-xL inhibitors, induces synergistic anti- BC cell activity. Moreover, not only the combination of EU-5346 with tamoxifen, trastuzumab as well as paclitaxel triggers synergistic anti- BC cell activity, but also inhibiting Mcl-1 overcomes resistance to paclitaxel in paclitaxel-resistant TNBC cells. Conclusions: Our data demonstrate an important role of Mcl-1 in BC cell survival, and provide the preclinical framework for the individualized, clinical use of Mcl-1-inhibitorbased drug combinations with antiapoptotic, antihormonal or chemotherapies to improve patient outcome in BC. Legal entity responsible for the study: Klaus Podar Funding: Eutropics Pharmaceuticals, Inc, Disclosure: M.H. Bashari: received research support from EUTROPICS. M.H. Cardone: employee of Eutropics, Inc. All other authors have declared no conflicts of interest. 13P Targeting unfolded protein response sensitizes urothelial carcinoma cells to cisplatin chemotherapy K.S. Han, J.J. Kim, J.G. Lee, J.J. Oh, S.C. Lee, S.E. Lee, S-S. Byun Department of Urology, Seoul National University Bundang Hospital, Gyeonggido, Republic of Korea Background: Chemotherapy deprives tumors of essential resources for cancer cell survival. These environmental stressors generally induce the accumulation of unfolded proteins in the endoplasmic reticulum (ER) of cancer cell. There, they elicit the unfolded protein response (UPR), which is a general cellular defense mechanism to protect cells from stress. We investigated a potential role of GRP78 as a combined therapeutic target in urothelial carcinoma. Methods: Urothelial cancer cell lines were used to investigate the effect of GRP78 knockdown, performed by small interfering RNA. Stably GRP78 knocked-down UC-3 cells were developed to investigate the role of GRP78 in cancer cell. After transient transfection, crystal violet assay and cell cycle analysis using FACS were performed to check the effect of GRP78 on tumor growth and cell cycle. In vivo system expressing GRP78 by doxycycline were developed using UC-3 xenografts and treated with cisplatin to evaluate in vivo combination effects of GRP78 inhibition during cisplatin. ix4 | abstracts Annals of Oncology Results: GRP78 was highly expressed in UC-3 cells and moderately expressed in T24, 253J and KU1919 cells. Immunohistochemical staining showed increased expression of GRP78 in human bladder cancer tissues compared with normal bladder tissues. Transient knockdown of GRP78 using si-GRP78 inhibited tumor proliferation in UC-3 cells. GRP78 knockdown also increased sub G0 population of UC-3 cells in cell cycle analysis and also induced more apoptosis after cisplatin treatment compared to control. Western blot analysis showed increased expression of GRP78 during exposure to cisplatin in bladder cancer cells. Sequential cisplatin treatment after knockdown of GRP78 showed an additive effect but sequential GRP78 knockdown after cisplatin chemotherapy showed a synergistic effect in UC-3 xenografts. Conclusions: GRP78 has a critical role in protecting urothelial carcinoma cells from apoptotic stress induced by chemotherapy. Targeting GRP78 sensitized urothelial carcinoma cells to cisplatin. These data suggest that GRP78 is a novel therapeutic target as a combination therapy with cisplatin in the management of urothelial carcinoma. Legal entity responsible for the study: Kyung Seok Han Funding: Korean National Research Foundation Disclosure: All authors have declared no conflicts of interest. 14P Adipose tissue-derived stem cells provide an advantageous tumor microenvironment in gastric cancer J. Kinoshita1, S. Fushida1, S. Harada2, K. Oyama1, T. Yamaguchi1, A. Hirose1, K. Okamoto1, K. Nakamura1, T. Miyashita1, H. Tajima1, H. Takamura1, I. Ninomiya1, T. Ohta1 1 Gastroenterological Surgery, Kanazawa University, Kanazawa, Japan, 2Center for Biomedical Research and Education, Kanazawa University, Kanazawa, Japan Background: Although recent evidence indicates the effect of tissue-resident stem cells located in the surrounding healthy tissue on tumor progression, little is known regarding the influence of adipose-tissue derived stem cells (ASCs) in gastric cancer. Methods: ASCs were isolated from surgical specimens of human omentum. Omental specimens were obtained from patients undergoing elective abdominal surgery according to procedures approved by the IRB of Kanazawa University. Informed consent was obtained from all patients. Female athymic BALB/c nu/nu mice were randomized into two treatment groups: (1) subcutaneous injection of MKN45 human gastric cancer cells or (2) subcutaneous injection of MKN45 mixed directly with ASCs. Tumor growth and volumes over the ensuing 2 weeks were assessed and immunohistochemistry was performed to investigate the influence of ASCs engrafted in tumor microenvironment. Results: At 2 weeks after injection, the mean tumor volume in the MKN45/ASCs coinjection group (427.36104.3 mm3) was significantly higher than that in MKN45- only group (194.6635.1mm3). The stroma in co-inoculated tumors consisted of fibrotic tissue, and the fibrous area was measured semi-quantitatively by Azan staining. The co-injection group showed a significant low ratio of fibrosis when compared with the MKN45-only group (p < 0.05). Immunohistochemical examination revealed the expression of a-SMA in the subcutaneous tumors was higher in the co-injection group, and the expression of Ecadherin was lower in the co-injection group than MKN45- only group. Conclusions: Our study revealed for the first time that ASCs subcutaneously coinjected with prostate cancer cells engraft and promote tumor progression. Legal entity responsible for the study: Jun Kinoshita Funding: Grant sponsor: Japan Society for the Promotion of Science (JSPS) Grant-inAid for Scientific Research; Grant number: 15K19876 Disclosure: All authors have declared no conflicts of interest. 15P Adipose tissue vascular promotes tumor growth rate and metastasis S. Lim MTC, Karolinska Institutet - Solna, Stockholm, Sweden Background: Many different types of cancer occur in adipose tissue environment that is highly vascularized. However, the role of adipose pre-existing vascular bed on tumor growth, angiogenesis and metastasis is unknown. Here, we report that pre-existing vascular density in adipose tissue environment is crucial for tumor takeoff, growth, angiogenesis and metastasis. Methods: EO771, B16 and T241 cell lines were implanted in the subcutaneous dorsal, white adipose tissue (WAT) or brown adipose tissue (BAT) of C57BL/6 mice. Tumor sizes were measured throughout each experiment. Tumor tissues were dissected, fixed in PFA, followed by whole mount staining or immunohistochemical staining to investigate blood vessels density (CD31), pericytes (NG2) coverage and perfusion (Dextran). Results: Implantation of 3 different cell lines including breast cancer, melanoma and fibrosarcoma into the subcutaneous tissue, white adipose tissue (WAT), and brown adipose tissue (BAT) demonstrated that the rate of tumor take off, tumor angiogenesis and growth, and metastasis are dependent on the degree of pre-existing vascularization Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology in these tissues. Tumor cells implanted in the BAT and WAT grew significantly faster than tumor cells implanted in the subcutaneous tissue. In addition, tumor cells implanted in the adipose tissues have increased neovascularization and blood perfusion, and their vasculatures are poorly coated with perivascular cell coverage resulting in increased leakage. Conclusions: Thus, our study shows that adipose vasculature predetermines the tumor microenvironment that supports tumor growth and progression. Legal entity responsible for the study: N/A Funding: The Swedish Research Council; the Swedish Cancer Foundation; the Karolinska Institute Foundation; the Karolinska Institute distinguished professor award; the Torsten Soderbergs foundation; the European Research Council (ERC) advanced grant ANGIOFAT (Project no 250021); the Knut Alice Wallenberg Foundation; the Novo Nordisk Foundation for the advanced grant; the Alex and Eva Wallströms foundation and the Lars Hiertas Minne foundation. Disclosure: All authors have declared no conflicts of interest. 16P Inhibition of invasion and migration by n-3 fatty acids in PC3 cells S. Ohta1, K-I. O-Ono1, T. Matsumura2, S. Taniguchi3 1 Faculty of Pharmaceutical Science, Josai University, Sakado, Japan, 2Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, School of Medicine, Matsumoto, Japan, 3Department of Comprehensive Cancer Therapy, Shinshu University, School of Medicine, Matsumoto, Japan Background: Recently, n-3 fatty acids have been shown to decrease the proliferation of cancer cells in colon cancer, breast cancer, hepatitic cancer, and neuroblastoma. Many studies have been carried out in relation to the growth of cancer cells. But few studies have examined invasion and metastasis in prostate cancer. Therefore, in this study, we investigated whether n-3 fatty acids (EPA and DHA) inhibit the proliferation, invasion, and migration of PC3 cells, which is an androgen-independent human prostate cancer cell line that is similar to castration-resistant prostate cancer. Our study was intended to explore a possible method for treating new castration-resistant prostate cancer. Methods: PC3 cells were cultured, and various concentrations of EPA or DHA were added. Cancer proliferation was confirmed by trypan blue microscopy. Invasion and migration assay were used in the upper chamber in PC3 cells, and serum-free medium and various concentrations of EPA or DHA were placed under plate in serum medium. Results: The effect of EPA on PC3 cells was dose-dependent; it was possible to obtain significant differences at concentrations of 100 and 200 mg/mL. The effect of DHA on PC3 cells has become the same as for EPA. In the migration assay, EPA showed almost identical results to the control at 25 mg/mL, but migration was reduced at 50 mg/mL. DHA showed the same results as EPA at 25 mg/mL and further reduction was observed at the 50mg/mL concentration. In the invasion assay, EPA did not show any difference to the control at a concentration of 25mg/mL, but suppressed the invasion at 50 mg/mL. DHA resulted in decreased invasion compared with the control at 25 mg/mL, and invasion was significantly reduced at a DHA concentration of 50 mg/mL. Conclusions: These substances restrained invasion and migration as well as proliferation of PC-3 cells. Their detailed mechanisms are not known, but part of the route has been elucidated. Legal entity responsible for the study: Shoichiro Ohta Funding: My Grants Disclosure: All authors have declared no conflicts of interest. 17P determined whether ELH suppresses tumor growth by using an in ovo xenograft model and whether it has the potential to control malignant tumors. Results: We found that ELH significantly suppressed p38, JNK, and NF-jB activation and proteolytic activities under phorbol 12-myristate 13-acetate (PMA) stimulation, thus leading to a decrease in metastatic potential, including migration and invasion. In addition, ELH suppressed tumor-induced angiogenesis, including migration and tube formation in HUVECs and microvessel sprouting from aortic rings via decreasing the pro-angiogenic factors in tumors. Interestingly, in ovo xenografts ELH-treated HT1080 cells did not increase in volume and eventually disappeared, owing to a lack of angiogenesis. Daily oral administration of ELH at 50 and 100 mg/kg markedly inhibited metastatic colonization of B16F10 cells in the lungs of C57BL/6J mice and caused no apparent side effects. Conclusions: These data collectively indicate that ELH is safe and may be useful for managing the metastasis and growth of malignant cancers. Legal entity responsible for the study: N/A Funding: Grant K15280 awarded to Korea Institute of Oriental Medicine (KIOM) from Ministry of Science, ICT and Future Planning (MSIP), Republic of Korea Disclosure: All authors have declared no conflicts of interest. Ethanol extract of Lophatheri Herba exhibits in vitro and in vivo anti-metastatic and anti-angiogenic activities in malignant cancer cells A. Kim, M. Im, E. Park, J.Y. Ma Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu, Republic of Korea Background: Lophatheri Herba (LH), the dried leaf of Lophatherum gracile Brongn, has long been used to reduce thirst and treat fever and inflammation in Chinese medicine. Recent studies have shown that LH has anti-viral, anti-bacterial, anti-cancer, anti-oxidant, diuretic, and hyperglycemic properties. However, the effects of an ethanol extract of L. herba (ELH), at non-cytotoxic doses, on the metastatic and angiogenic abilities of malignant tumor cells have not been reported. Methods: In the present study, we examined the influence of an ethanol extract of LH (ELH) on the metastatic and angiogenic properties of malignant tumor cells by using in vitro assays, an in vivo pulmonary metastasis model, ex vivo aortic ring assays, and in ovo chick chorioallantoic membrane (CAM) assays. Furthermore, we studied the underlying mechanisms of the anti-metastatic and anti-angiogenic activities of ELH and Volume 27 | Supplement 9 | December 2016 18P TC-1 is required for TBC1D3-induced Wnt/beta-catenin accumulation and cell migration in MCF-7 breast cancer cells H. Zhao Immunology, Zhongda Hospital Southeast University, Nanjing, China Background: TC-1 was originally found in thyroid cancer and it was subsequently demonstrated that TC1 up-regulates Wnt/beta-catenin target genes implicated in invasiveness and aggressive behavior of cancers in many tumors. TBC1D3 is a hominoid-specific gene that was originally identified as a novel amplified oncogene, based on its ability to confer tumorigenicity to NIH 3T3 cells. TBC1D3 highly overexpresses in breast cancer, while its function in the development and progress of tumors remains unknown. Methods: Human breast cancer MCF-7 cells were transfected with or without the FlagTBC1D3 plasmid and then transcriptome sequencing was performed. ShRNA-NC/MCF-7 cells and shRNA-TC-1/MCF-7cells were established and identified. Then two establishment steady cells were transfected with or without the Flag-TBC1D3 plasmid, and then 10 104 cells of each group were performed with transwell assay treating with XAV939(Wnt/betacatenin inhibitor) or not; other cells were lysed with RIPA and immunoblotted. Results: The transcriptome sequencing assay showed that TBC1D3expression upregulates TC-1 and beta-catenin mRNA levels. Western blot showed that TBC1D3 expression up-regulates TC-1 and beta-catenin protein levels. ShRNA against human TC-1knocked down TC-1 expression by more than 80% and was assessed by immunoblotting in MCF-7 cells. When TC-1 was knocked down, the TBC1D3-induced up-regulation of beta-catenin was reduced. Otherwise, there was no effect on TBC1D3induced up-regulation of TC-1 after treating with XAV939. Transwell assay showed the migration number of MCF-7 cells transfected with TBC1D3 plasmid was 90 6 10, which is higher than the control group, and the difference was significant (P < 0.05). Furthermore, TBC1D3-induced MCF-7 cells migration decreased when treated with XAV939 or knocked down against TC-1 Conclusions: TC-1 is required for TBC1D3-induced Wnt/beta-catenin accumulation and cell migration in MCF-7 breast cancer cells. Legal entity responsible for the study: N/A Funding: Natural Science Foundation of China Disclosure: All authors have declared no conflicts of interest. 19P Curcumin oleoresin inhibits cell growth and migratory properties of breast cancer cells through inhibition of NF-kB pathway A. Avan1, S. Shahidsales2, Z. Bahmani3, F. Ghasemi4, S.M. Hassanian5, A. Sahebkar6 1 Department of Modern Sciences and Technologies, Mashhad University of Medical Sciences, Mashhad, Iran, 2Cancer Research Center, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran, 3Department of Modern Sciences and Technologies, Mashhad University of Medical Sciences, Mashhad, Iran, 4Department of Medical Biotechnology, Mashhad University of Medical Sciences, Mashhad, Iran, 5 Department of Medical Biochemistry, Mashhad University of Medical Sciences, Mashhad, Iran, 6Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Background: Curcumin is a polyphenolic compound derived from Curcumin longa L. There is growing body of data showing the antitumor effect of curcumin in different cancers; however, the molecular mechanism underlying of this inhibition in breast doi:10.1093/annonc/mdw573 | ix5 abstracts cancer is still remained to be elucidated. Here we investigated the antitumor activity of curcumin alone or in combination with paclitaxel or doxorubicin in MCF-7 cells in monolayer cell cultures and spheroids models. Moreover, the cytotoxic activity of three different forms of curcumin (phytosomal), phospholipidated curcumin, amorphous curcumin and turmeric oleoresin were evaluated, compared to unformulated curcumin. Methods: The antiproliferative activity of 4 different forms of curcumin was assessed in monolayer and spheroid models of MCF-7 cells. The cell cycle modulation and migratory behaviors of the cells were determined by FACS and migration assay before and after treatment with curcumin. The expression levels of survivin, CyclinD1, MMP3, MMP9, P65, P21, Nf-kB, and E-cadherin were studied by quantitative RT–PCR and/or western blot. Results: Ccurcumin suppressed cell growth in MCF-7 cells at 110uM IC50 value. The median drug-effect analysis showed a slight-to-moderate synergism with CI values of 0.8. Curcumin was able to reduce the invasiveness of MCF-7, compared to control cells. Moreover, curcumin inhibited the tumor growth in MCF-7 cells, although this inhibition was more pronounced with amorphous/phospholipidated curcumin. Additionally, curcumin significantly (P < 0.05) increased the percentages of the cells in S and G2/M phases (e.g., from 15.2 in the control to 18.4% in the S phase) after 72 hours, while reducing the percentage of the cells in G0/G1. Analysis of the sub-G1 region of cell cycle analysis revealed that the treatment with curcumin increased cell death through modulation of NF-kB pathways. Conclusions: We demonstrated the antitumor activity of curcumin and its curcumin oleoresin in a breast cancer cell line, supporting further investigations on the therapeutic potential of this novel anticancer agent in in vivo models. Legal entity responsible for the study: N/A Funding: Mashhad University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. 20P Verification of mechanism that CSC markers are implicated in poor prognosis for pancreatic ductal adenocarcinoma K. Arima1, T. Ishimoto1, M. Ohmuraya2, H. Okabe1, Y. Kitano1, K. Yamamura1, T. Kaida1, S. Nakagawa1, K. Imai1, D. Hashimoto1, A. Chikamoto1, Y-I. Yamashita1, H. Baba1 1 Department of Gastroenterology, Kumamoto University, Kumamoto, Japan, 2 Department of Genetics, Hyogo College of Medicine, Nishinomiya, Japan Annals of Oncology 21P T. Ishimoto1, K. Miyake2, T. Nandi1, M. Yashiro3, K.K. Huang1, K. Arima2, D. Izumi2, Y. Baba2, H. Baba2, P. Tan1 1 Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, 2Department of Gastroenterological Surgery, Kumamoto University, Kumamoto, Japan, 3Department of Surgical Oncology, Osaka City University Medical School, Osaka, Japan Background: Cancer-associated fibroblasts (CAFs) have been reported to promote various types of tumor through secretion of soluble factors. However, there have been no systematic studies of CAFs in diffuse-type gastric cancers (DGCs). We investigated the characteristics and functional roles of CAFs in DGCs using comprehensive genomic approach. Methods: Normal fibroblasts (NFs)/CAFs were subjected to Exome and RNA sequencing, and the possible candidates for functional assay were selected from among the acquired comprehensive data. The candidate molecules were examined the functional roles for GC tumor progression by in vitro assays. Results: The differential expression analysis revealed that the expression of 34 genes were significantly up-regulated in CAFs compared with those in NFs. Furthermore, the pathway analysis showed that cytoskeletal signaling pathway was up-regulated and TGFb1 played crucial roles as one of upstream regulators in CAFs. Real-time imaging showed that the motility of CAFs was significantly greater on extracellular matrix. Intriguingly, the motility of CAFs conferred invasiveness on GC cells co-cultured with CAFs. Conclusions: Comprehensive genomic analyses revealed that CAFs show an invasive molecular pattern. The findings in current study also suggests that CAFs in DGCs exhibit a particular motility associated with TGFb1 signaling and are intimately involved in GC invasion. Legal entity responsible for the study: N/A Funding: Japan Society for the Promotion of Science (JSPS), KAKENHI Grant Disclosure: All authors have declared no conflicts of interest. 22P Background: Cancer stem cells (CSCs) refer to a subset of tumor cells that have selfrenewal ability and generate plenty of non-CSC cells that comprise a tumor. Aldehyde dehydrogenase 1 (ALDH1), c-Met, and CD44 have been identified as CSC markers in pancreatic ductal adenocarcinoma (PDAC). On the other hand, prostaglandin E2 (PGE2) is one of metabolites in arachidonate cascade and is implicated in the expansion of hematopoietic and tissue stem cell fraction. The aim of this study is to single out the most important CSC marker and elucidate the functional role of PGE2 for CSC expansion in PDAC. Methods: Three CSC markers (ALDH1, CD44, and c-Met) expression was examined by immunohistochemistry in 121 primary surgical specimens of PDAC and analyzed a relationship with clinicopathological factors and clinical outcomes. The clonogenic growth potential of CSC marker-positive PDAC cells was assessed in vitro by growth assays and sphere formation assays. We next investigated the expression of CSC markers and self-renewal related genes in PDAC cell lines with PGE2 or 15-PGDH inhibitor treatment. We further conducted functional experiments using siRNA to identify the critical molecule in PDAC progression. Results: A high level of ALDH1 expression was detected in 63 of the 121 cases, and was significantly associated with large tumor size and poor prognosis in PDAC patients. On the other hand, CD44 and c-Met expression were not associated with the prognosis. Among CSC markers, the expression of ALDH1 was significantly increased by PGE2 treatment in PDAC cells. By suppressing ALDH1 expression by siRNA, growth and sphere formation potential were inhibited in ALDH1 high-expressing PDAC cells. In contrast, the expression of ALDH1 was remarkably increased by PGE2 or 15-PGDH inhibitor treatment in PDAC cells. Finally, we found that Nanog was a down-stream molecule of PGE2-ALDH1 signaling and played crucial roles for PDAC cell expansion. Conclusions: Our results demonstrated that PGE2 positively regulated ALDH1 expression, and the growth and sphere formation potential were promoted by increasing ALDH1 expression, resulting in poor prognosis of PDAC patients. Inhibiting PGE2-ALDH1 signaling could lead to the suppression of tumor growth in PDAC patients. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. ix6 | abstracts Identification of the novel molecules mediating gastric cancer invasion based on genomic analysis of cancer-associated fibroblasts Global epigenetic remodeling regulates chemoradiotherapy sensitivity of cancer J. Li, D. Hao, Y. Wang, L. Wang, Z. Zhao, P. Li, L. Di Faculty of Health medicine, University of Macau, Macau, China Background: Targeting epigenetics has great potential in treating cancers with aberrant oncogene or tumor suppressor expression caused by deregulated epigenetic modifications. The FDA has approved seven epigenetic drugs (EDs) with indicated application on hematological malignancies. The potential use of EDs in solid tumors is also actively under investigation. Current ideas about EDs are largely based on the assumption that EDs are supposed to reverse repressed tumor suppressors. Methods: We summarized ETDs clinical trials till now and performed meta-analysis. Gene expression enrichment analysis indicated the genome profile of oncogenes and tumor suppressors affected by ETDs. We explored MNase assay, MTT assay, Immunofluorescence to confirm the mechanism that ETDs increased DNA targeted drugs (DTDs) accessibilities to nuclei. Exnograftes NOD/SCID mice were created to assess the effect of DTDs combined with ETDs. Results: ETDs show surprisingly limited effect (0% CR and 2% PR among 1153 cases) in clinical solid tumors therapies. However, the curative effects of ETDs delivered together with DTDs are quite encouraging according to meta-analysis. Gene expression profiling revealed significant amount of differentially expressed genes which are not solely limited to tumor suppressor genes, arguing that the mechanism of ETDs in treating hematopoietic cancers should be carefully reconsidered. We found both HDAC inhibitor (SAHA) and DNMT inhibitor (Decitabine) loosen chromatin through enhancing histone acetylation and reducing DNA methylation respectively. Increased chromatin integration of cisplatin or doxorubicin and enhanced cell death were observed. Xenografted tumors in NOD/SCID mice showed increased sensitivity to DTDs combined with ETDs. Conclusions: Given the limited effect of EDs alone, these results strongly suggest that the combination of DNA targeting chemos or irradiation and the epigenetic targeting drugs is a very promising choice in clinical tumor therapy. Legal entity responsible for the study: Faculty of Health Science, University of Macau Funding: Research Grant Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology 24P Establishment of patient-derived xenografts from malignant pleural effusion using NOG mice T. Chijiwa1, M. Haraguchi2, T. Isagawa3, A. Noguchi4, M. Katayama5, N. Miyao2, M. Yoshioka2, N. Matsui6, Y. Tateishi7, H. Suemizu7, R. Yamada8, Y. Nakamura8, K. Imai8, D. Komura3, H. Katoh3, S. Ishikawa3, M. Nakamura9, Y. Miyagi8 1 Department of Emergency and Critical Care Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan, 2Department of Internal Medicine, Nihon Koukan Hospital, Kawasaki, Japan, 3Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan, 4 Department of Pathology, St. Marianna University School of Medicine, Kawasaki, Japan, 5Department of Neurosurgery, Kawasaki Municipal Hospital, Kawasaki, Japan, 6Department of Pathology, Nihon Koukan Hospital, Kawasaki, Japan, 7Laboratory Animal Research Department, Central Institute for Experimental Animals, Kawasaki, Japan, 8Research Institute, Kanagawa Cancer Center, Yokohama, Japan, 9Department of Regenerative Medicine, Tokai University School of Medicine Isehara Campus, Isehara, Japan Background: Personalized medicine represents an ideal medical approach for cancer therapy. Xenografts derived from engrafting fresh surgical specimens directly into immunodeficient mice have recently enabled the development of more relevant in vivo models for human tumors. Patient-derived xenograft (PDX) models retain similar morphologies, heterogeneities, and molecular signatures to the original cancers, and, thus, may be used in the rapid screening of potential therapeutics. We previously reported the rapid and efficient establishment of PDXs using super-immunodeficient NOG mice (PDX/NOG). Surgical specimens are clearly necessary for establishing individual PDX/NOG using personalized medicine. In this study, we attempted to establish PDX/NOG from malignant pleural effusion (MPE) and investigated the potential of MPE-PDX/NOG for personalized anti-cancer therapies. Methods: All MPEs were obtained from therapeutic thoracentesis with the informed consent of patients. Cell pellets combined with cancer cells and unarranged cells were generated by centrifuging MPE, and were then inoculated subcutaneously into NOG mice. The established xenograft models were confirmed pathologically after tumor tissue had been passaged three times by subcutaneous engraftment. The preservation of cancer stem cells (CSCs) was confirmed by immunohistochemical and gene expression analyses. Results: We established 2 MPE-PDX/NOG lines (pulmonary adenocarcinoma) from 4 cases. These lines showed the histological structures of well-differentiated adenocarcinoma with murine stromal formation. The morphological characteristics of MPE-PDX/NOG were maintained for cellularity and structural heterogeneity. CSC markers (CD44, ALDH1A1, and EpCAM) were preserved in MPE-PDX/NOG tissue. Conclusions: The establishment of PDX/NOG from MPE is efficient and as valuable as that from surgical specimens. Serial MPE-PDX/NOGs may be less invasively established from the same patient because patients with MPE may repeatedly undergo therapeutic thoracentesis. The analysis of serial MPE-PDX/NOGs will disclose characteristic changes in cancer cells affected by chemotherapies and contribute to personalized medicine. Legal entity responsible for the study: Jichi Medical University Funding: JSPS Grant-in-Aid for Scientific Research Disclosure: All authors have declared no conflicts of interest. 25P Review of reproductive risk factors in breast cancer patients in Toungoo General Hospital, Myanmar K.K.K. Nwe1, S. Aung2, S. Mon3, T.T. Aye3 Medical Oncology Unit, Taungoo General Hospital, Taungoo, Myanmar, 2 Medical Oncology Unit, Yangon General Hospital, Yangon, Myanmar, 3Medical Oncology Unit, Bahosi Medical Centre Bahosi Housing Complex, Yangon, Myanmar 1 Background: Breast cancer is the most common cancer in Myanmar women. International studies proved that reproductive factors such as nulliparity and older age at first full-term pregnancy increase the risk of developing breast cancer. Breastfeeding can lower breast cancer risk, especially if a woman breastfeeds for longer than one year. We studied the reproductive risk factors of breast cancer patients in Toungoo district, which is situated in lower central part of Myanmar with various races and ethnicities. Methods: A cross-sectional, hospital based study was carried out in medical oncology unit, 200 bedded Toungoo General Hospital from January 2012 to July, 2016. Results: Among (210) breast cancer patients registered, only one male patient was noticed. In (209) female patients, age range from 28-91 yrs (median 52.47 yrs). Invasive duct carcinoma 208 [99.52%] and one invasive lobular [0.47%] were found. The most common stages were II B 60 [28.7%] and III A 53 [25%] in this study. Patients with first full-term pregnancy at later age (after 30yrs) were 35 [16.75%]. Among 141 mothers, 140 [99.29%] did breast feeding to their children more than one year duration. Volume 27 | Supplement 9 | December 2016 Table: 25P Parity and breast cancer patients Parity Patients [%] Single/P0 P1 P2-4 P5 68 [32.53%] 11 [5.26%] 95 [45.45%] 35 [16.75%] Conclusions: In this study, it was found that almost all parous women with breast cancer did breastfed their babies in longer duration more than one year. A few patients had first full-term pregnancy after 30year of age and a large number of patients were parity two and more. These data highlights that the breast cancer risk factors in Myanmar women have slight variation from international findings. Further studies with larger sample size with control group should be conducted to find out associated breast cancer risk factors in Myanmar women. Legal entity responsible for the study: Medical Oncology Unit, Toungoo General Hospital Funding: Toungoo General hospital Disclosure: All authors have declared no conflicts of interest. 26P Pre and post chemotherapy circulating oxidative stress parameters in breast cancer patients D. Moslemi1, S. Mahjoub2, M. Taherkhani2, A. Karkhah2 Radiation Oncology, Babol University of Medical Sciences (BUMS), Babol, Iran, 2 Biochemistry, Babol University of Medical Sciences (BUMS), Babol, Iran 1 Background: Previous studies have suggested the importance of serum oxidant/ antioxidant status in initiation and progression of breast cancer. The present study aimed to evaluated oxidative and nitrosative stress markers in breast cancer patients and the impact of age and clinical stage on these variables before and after three cycle chemotherapy using AC-T Methods: This study included 60 women with newly diagnosed breast cancer in stage II, III who underwent AC-T chemotherapy regimen as the first therapy after surgery. Serum samples were obtained before treatment and after three cycles of chemotherapy. Then, the serum status of total antioxidant status (TAS), thiobarbituric acid reacting substances (TBARS), carbonyl proteins content and total nitric oxide (NOx) were analyzed by spectrophotometry. In addition, BMI was measured and analyzed according to age-related effects and clinical stage of the disease. Results: A concurrent increase in TBARS, carbonyl, NOx and a significant decrease in TAS were also observed after third course of chemotherapy using AC-T. In addition, these findings indicated that there was not a significant change in BMI of patients after three cycle chemotherapy using AC-T, whereas some changes were found in the status of oxidative and nitrosative stress markers which were associated with age and clinical stage of the disease Conclusions: Our data indicated that AC-T chemotherapy regimen increases the oxidative and nitrosative stress in breast cancer patients. Therefore, monitoring of serum oxidative and nitrosative markers may be helpful for screening of breast cancer patients with high risk of early disease progression and predictive or prognostic markers Legal entity responsible for the study: Babol University of Medical Sciences Funding: Babol University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. 27P Pectin-Chitosan conjugates novel biomaterial as platform for colon cancer drug delivery A.V. Singh Materials Engineering, Indian Institute of Science, Bangalore, India Background: In comparison to injectable, oral delivery of chemotherapeutic agents, especially in the form of a colon specific delivery system is expected to increase drug bioavailability at target site, reduce drug dose and systemic adverse effects. Pectin (PEC) and Chitosan (CS) are suitable and well documented independently drug delivery polymers for use as colon specific drug delivery as it is selectively digested by colonic microflora to release drug with minimal degradation in upper gastrointestinal tract. Pectin chitosan bioconjugate has not been synthesized and well studied for their suitability in colon cancer drug delivery applications; hence we have attempted to synthesize PEC-CS conjugate system. Methods: Pectin-chitosan conjugate system was developed by conjugating the free carboxyl group of moiety of pectin and primary amine group of CS. Synthesized material was characterized by FTIR, XRD, DSC, TGA and SEM. Cancer cell toxicity study of the synthesized material were done in HT29 colon adeno- carcinoma cell lines using MTT assay. doi:10.1093/annonc/mdw573 | ix7 abstracts Results: Pectin reacts with –NHS to form an ester in presence of DCC in anhydrous conditions along with the side product dicyclohexylurea, and finally CS reacts with this mixture replacing NHS to form the conjugate. The peaks in the region 1709 cm1 and 1641 cm1 corresponds to weak carbonyl stretch due to H-bonding and the amide-I band of the formed conjugate. Also seen in the FTIR spectra is the peak belonging to amide-II band of secondary amides at 1554 cm1 and C-C ring stretch at 1509 cm2. The conjugate showed significantly low weight loss till 300 C (23.6%) as compared to PEC. The above result opined that PEC-CS exhibited high thermal stability as compared to its native precursor. The plain PEC showed its Tg at 69.55 C, while in PEC-CS it was observed at 55.13 C. This result confirms that movement of molecule in PEC-CS is unhindered as compared to in PEC. The conjugation was confirmed by FTIR, and XRD. The DSC and TGA analysis exhibited formation of a more thermostable material as compared to its native precursors. The conjugated material did not exhibit any cytotoxicity in HT29 cells. Conclusions: The results showed a potential to be used this novel conjugate material for colon cancer drug delivery application. Legal entity responsible for the study: Akhilesh Vikram Singh Funding: UGC-MHRD, New Delhi, India Disclosure: A.V. Singh: The presented work is purely academic research and funded by Government of India (UGC-MHRD, New Delhi). 582P Cardioprotective effects of pentoxifylline on ventricular fibrillation and fibrosis in rat model of radiation-induced heart abnormalities Annals of Oncology the side effects in cancer therapy, typically, enhancement of the heart fibrosis and infarction. Radiation-induced heart abnormalities (RHAs) can appear as long-term side effects when all or even a part of the heart are influenced by radiation in breast or lung cancer patients. Methods: Thirty-four rats were randomly divided into four groups: (I) control (n ¼ 5); healthy animals without any manipulation, (II) radiation (n ¼ 7); animals underwent irradiation for 5 sessions for a total dose of 1200 centigray gamma-rays for two weeks, (III) PTX (n ¼ 11); animals treated with PTX (95-105 mg/kg/day) which added to drinking water with Vit E (5.5 mg/kg/day, i.p) for 6 weeks. Results: Key findings: RAD decreased significantly heart rate, force of contraction, LVDP RPP, þdP/dt max and dP/dt min, but increased dramatically LVEDP compared with the control group, and PTX significantly restored these parameters. RAD caused an increase in VF by decreasing its threshold. The lung and heart fibrosis changes have appeared in radiated animals, after 27 weeks irradiation which was reversed by PTX. Immunohistochemistry examinations of the heart sections showed high Bax and low Bcl-2 expressions in RAD and PTX groups compared with control. Conclusions: Significance: The present study shows that pre-treatment withPTX in radiation-induced heart abnormalities can decrease fibrosis and VF. The findings suggest that PTX has an impactful protective effect on heart abnormalities. Legal entity responsible for the study: Emam Khomeini Hospital, Research Center, Institute Cancer Funding: Emam Khomeini Hospital, Research Center, Institute Cancer Disclosure: All authors have declared no conflicts of interest. A.M. Safaie, E. Esmati Institute Cancer, Central Cancer Institute of Imam Khomeini Hospital, Tehran, Iran Background: Recent technologies of cancer radiotherapy have enhanced the survival rate of patients in the last decades. However, radiation exposure may increase the risk of ix8 | abstracts Volume 27 | Supplement 9 | December 2016 Annals of Oncology 27 (Supplement 9): ix9–ix18, 2016 doi:10.1093/annonc/mdw574 Biomarkers 30P HOTAIR induces EGFR-TKIs resistance in non-small cell lung cancer via epithelial-mesenchymal transition N. Cheng1, Q. Wang2, W. Cai2, S. Ren2, X. Li2, C. Zhao2, C. Zhou2 1 Oncology cencer, 1st Shanghai People’s Hospital, Shanghai, China, 2Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China Background: Previous research found that HOTAIR, a long non-coding RNA, is aberrantly expressed and associated with tumor invasion, metastasis and chemoresistance in many cancers. The aim of this study was to investigate the role of HOTAIR in resistance of EGFR-TKIs in NSCLC. Methods: HOTAIR expression level was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in NSCLC cell lines or tumor tissues. A total of 52 samples with EGFR-mutant and EGFR-TKI-sensitive NSCLCs, 42 with acquired resistance and 46 with primary resistance to EGFR-TKIs were analyzed. The effect of HOTAIR on cell proliferation and apoptosis was investigated by CCK-8 and flow cytometry assays. The expression of EMT proteins was assessed by western blot. Results: HOTAIR was significantly down-regulated in lung cancer cells (PC9/R, H1975, H1299 and A549) and patients with primary and acquired resistance to EGFR-TKIs. In the clinical setting, high levels of HOTAIR expression was significantly correlated with longer progression-free survival (PFS; P < 0.01) compared with low HOTAIR expression subgroup in tumors with respond to EGFR-TKIs. In vitro, over-expression HOTAIR could restore gefitinib sensitivity in gefitinib-resistant cells (PC9/R, H1299 and A549), but this change in sensitivity was not observed in H1975. Up-regulated HOTAIR induced cell apoptosis in PC9/R, H1299 and A549, and activated epithelialmesenchymal transition (EMT). Conclusions: HOTAIR expression was associated with primary and acquired resistance to EGFR-TKIs and could regulate cell proliferation through activating cell apoptosis and EMT, which suggest that HOTAIR might act as a biomarker to predict the EGFRTKI resistance. Legal entity responsible for the study: CSCO Funding: CSCO Disclosure: All authors have declared no conflicts of interest. 29PD Downregulation of FBP1 promotes tumor metastasis and indicates poor prognosis in gastric cancer via regulating epithelial-mesenchymal transition J. Li, J. Tong Department of Oncology, Yangzhou NO.1 People’s Hospital, The Second Clinical School of Yangzhou University, Yangzhou, China Background: Recent studies indicated that some glycolytic enzymes are complicated, multifaceted proteins rather than simple components of the glycolytic pathway. FBP1 plays a vital role in glucose metabolism, but its role in gastric cancer tumorigenesis and metastasis has not been fully understood. Methods: The prognostic value of FBP1 was first studied in The Cancer Genome Atlas (TCGA) database and validated in an in-house database. The effect of FBP1 on cell proliferation and metastasis was examined in vitro. Nonparametric test and Log-rank test were used to evaluate the clinical significance of FBP1 expression. Results: In the TCGA cohort, FBP1 mRNA level were shown to be predictive of overall survival in gastric cancer (P ¼ 0.029). In the validation cohort, FBP1 expression wasinversely correlated with advanced N stage (P ¼ 0.021) and lymphovascular invasion (P ¼ 0.011). Survival analysis demonstrated that FBP1 was an independent predictor for both overall survival (P ¼ 0.004) and disease free survival (P < 0.001). Functional studies demonstrated that ectopic FBP1 expression inhibited proliferation and invasion in gastric cancer cells (P < 0.05). Mechanically, FBP1 serves as a tumor suppressor by inhibiting epithelial-mesenchymal transition (EMT). Conclusions: In conclusion, downregulation of FBP1 promotes gastric cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in gastric cancer. Legal entity responsible for the study: JIng Li Funding: N/A Disclosure: All authors have declared no conflicts of interest. Correlation between Ki-67 expression and clinic-pathological features of soft tissue sarcomas in the extremities M. Kelany, S. Abdelwahab, E. Saleh, A. Gaballa, F. Sayed Clinical oncology, Ain Shams University Faculty of Medicine, Cairo, Egypt Background: Soft tissue sarcomas (STSs) are a rare heterogeneous disease, Ki-67 is a nuclear protein highly expressed in the proliferative state of somatic cycle. We studied the prognostic value of Ki-67 expression and its primary tumor characteristics in adult patients with extremity STSs. Methods: We retrospectively collected the clinical data of 40 patients with extremity STSs treated at Ain Shams university hospital from January 2010 to December 2012 and we correlated between Ki-67 expression by immunohistochemistry and the clinicopathological data. We used a cutoff value of 20% for Ki-67 in tumor cells. The differences among variables were calculated by chi-quare test. Results: High Ki-67 expression (>20%) was found in 20% of cases (8/40). High Ki-67 was significantly correlated with age > 50 years old (p < 0.002), grade (p < 0.023), local recurrence (p < 0.009) and distant metastasis (p < 0.001). multivariate analysis indicated that high Ki-67 expression was a significant independent prognostic factor for median DFS (12 months vs 4 months for low and high Ki-67 respectively with (P ¼ <0.006, Cl 95% 7.87–14.13) and median OS was 28 months vs 10 months, respectively (P ¼ 0.001, Cl 95% 12.45–35.55). Conclusions: In our study we found that high expression of Ki-67 protein >/20% in extremity STSs, is frequently associated with poor prognosis, including the occurrence of distant metastases. Clinical trial indentification: the trial approved by Ain Shams University Faculty of medicine Research Ethics Committee on 25 November 2014 with numder¼ FMASU 3080/2014 Legal entity responsible for the study: Mohamed Kelany Funding: Our own funding Disclosure: All authors have declared no conflicts of interest. 31P Molecular mechanisms of regulation of proliferation markers of breast cancer in young patients L.T. Zakirova Mammology, National Cancer Research Center of Uzbekistan, Tashkent, Uzbekistan Background: Complete tumor regression (stage IV) is accompanied by the highest rates of overall survival (OS): 5-year, and 15-year survival in patients of this group is 92.3% and 83.1%, respectively. In contrast, in low pathomorphism OS for the same period was 42.3% and 28.7%, respectively. Methods: We investigated the tissue samples taken during trephine biopsies of breast tumors in 54 women with breast cancer with the mean age of 28-35 years with histologically verified malignant tumors of the mammary glands. Spectrum of markers in tissue samples comprises determination of the degree of tumor malignancy, the level of Ki-67 expression, mitotic index, and cell fraction in S-phase. Results: We found that the most sensitive to cytotoxic drugs were proliferating pool of cells and cells in S-phase. The 3rd degree of histological malignancy, Ki 67 expression level> 30% associated with a greater probability of complete regression of tumors in response to chemotherapy. Poorly differentiated cancers are more sensitive to chemotherapy; the frequency of complete morphological effects is directly proportional to the degree of anaplasia: at tumor grades 1 and 2 the complete pathologic response rate is only 10%, but in highly aggressive tumors when chemotherapy is used it increases up to 90%. In our study, estrogen receptor status appeared an independent factor which predicted complete pathomorphological response and favorable remote results. When comparing the significance of proliferation markers, the significantly predictive value were indicators such as cell fraction in S-phase, mitotic index, the level of Ki 67. The most important value for complete pathomorphism was mitotic index: when its level was more than 17 to 3.3 mm2 pCR rate reached 50%, and at the levels which were below the threshold – just 7%. Conclusions: Thus, when mitotic index decreased significantly even at large size of residual tumor, the prognosis of the disease is relatively favorable. In cases where high mitotic index and Ki 67 index are associated with gene p53 mutation, the likelihood of C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts 28PD abstracts significant effect of neoadjuvant chemotherapy is very low, and remote results of treatment are significantly worse. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 32P Heterogeneity analysis of DW MRI as a biomarker for prediction of overall survival and 6 month PFS in GBM patients M. Beigi1, A. Fathi Kazerooni1, M. Safari1, A. Ameri2, B. Moini3, M. Shojaee Moghdam4, H. Salighehrad1 1 Medical Engeenering and Medical physics, Tehran University of Medical Sciences, Tehran, Iran, 2Radiation Oncology, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 3Radiation Oncology, Emam Hosein Hospital, Tehran, Iran, 4Imaging, Day Hospital, Tehran, Iran Background: GBM is the primary malignant brain tumors with median patient survival of 12-15 months. Intratumoral heterogeneity causes to variable behavior of tumor and response to treatment. Anatomical MRI are not capable of providing information about tumor matrix. Diffusion-weighted (DW) MRI provide physiological information by quantifying the water diffusivity within tumor. The aim of this study was to evaluate the use of texture analysis of DWI for prediction of overall and 6 month progression free survival of patients. Methods: 11 patients with GBM who were referred to Jorjani Center (2012 -2014), were selected. All patients gave their written informed consent. Routin and DW MRI were performed before treatment. Apparent diffusion coefficient (ADC) maps were generated from DW images. T2 FLAIR images were registered to ADC map. ROI was placed on tumor region in T2FLAIR images. The ROI’s masks were transferred to inhouse programs in MATLAB. The heterogeneity of the GBM were explored by firstorder histogram of ADC included: histogram standard deviation, smoothness, third moment, uniformity, entropy, kurtosis, Percentile25, Percentile75 and Percentile95. Results: Positive correlation was seen between Percentile25, Percentile75 and Percentile95 with overall survival that were statistically significant (p < 0.05): p ¼ 0.047, p ¼ 0.041 and p ¼ 0.01 respectively. 6-PFS of patients were acquired using follow up MRI and best pretreatment parameters to classify patients with 6-month PFS from patients without PFS were acquired using discriminant analysis. Percentile25 is the best parameter to discriminate two groups (Wilks’ lambda¼0.702). Conclusions: Heterogeneity metrics of DWI were explored to obtain the most accurate predictive biomarker for theraputic outcome. The positive correlation of above mentioned parameters implies that tumors with higher mentioned metrics will respond better to therapy and longer overall survival. These results demonstrate the feasibility of heterogeneity analysis of DW MRI for pre-treatment prediction of outcome undergoing radiation therapy and will be validated in twenty-eight population to determine which metrics can be adopted as relevant biomarkers for outcome prediction of GBM. Legal entity responsible for the study: Tehran University of Medical science Funding: Tehran University of Medical science Disclosure: All authors have declared no conflicts of interest. 33P Somatic mutations of PIK3CA and AKT1 in Japanese breast cancer T. Shimoi1, A. Hamada2, Y. Kitamura1, T. Nishijo2, A. Shimomura1, C. Shimizu1, M. Yoshida3, T. Kinoshita4, Y. Fujiwara1, K. Tamura1 1 Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan, 2 Department of Clinical Pharmacology, Fundamental Innovative Oncology Core, National Cancer Center Research Institute, Tokyo, Japan, 3Departement of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan, 4Departement of Breast Surgery, National Cancer Center Hospital, Tokyo, Japan Background: PI3K/AKT/mTOR pathway regulates cell proliferation, growth and survival. The PIK3CA mutation is one of the most frequent somatic mutation in breast cancer and its frequency is about 30%. The AKT1 mutation is considered to be drivers of human breast cancer, and frequency is about 3%. However, there are few reports about frequencies in Asian breast cancer population. We tried to reveal the frequency of the PIK3CA and AKT1 mutations in the Japanese cohort. Methods: We retrospectively analyzed 337 samples from breast cancer patients who were treated in National Cancer Center Hospital. We extracted DNA and determined three hotspot PIK3CA mutations (E542K, E545K, H1047R) with quenched probe system, or AKT1 E17K mutation with PNA-LNA clamp methods. Differences between proportions for categorical variables were analyzed using the chi-square statistic. Kaplan-Meier analysis was performed to analyze event-free survival (EFS) after surgery and overall survival (OS). Results: We analyzed PIK3CA mutation in 334 samples or AKT1 mutation in 329 samples, from breast cancer patients who was treated between January 2008 and June 2015. Three hundred and five patients were initially stage I to III, and thirty-two ix10 | abstracts Annals of Oncology patients were initially StageIV. The number of tumor subtype was hormone receptor (HR) positive and HER2 negative tumor; 248 (74%), HR positive and HER2 positive tumor; 44 (13%), HR negative and HER2 positive tumor; 28 (8%), and Triple negative tumor; 17 (5%), respectively. The median age was 52 (range 22-90). There are 176 relapses and 32 deaths. We could detect 111 patients with PIK3CA mutations (33%) in 334 patients and 24 patients with AKT1 mutation (7.3%) in 329 patients. Twenty patients (6%) had E542K mutation, 21 patients (6%) had E545K mutation and 74 patients (22%) had the H1047R mutation. PIK3CA mutations were no difference between the four subtypes, however, AKT1 mutation was highly frequent in HR positive HER2 negative breast cancer (p ¼ 0.038). PIK3CA mutation was a statistically significant good prognostic factor by EFS (p ¼ 0.018), especially at the spot of H1047R (p ¼ 0.008), but not by OS. Conclusions: Although the frequency of PIK3CA mutation was equivalent between races, AKT1 mutation seemed to be more frequent in Japanese than in Caucasian. Legal entity responsible for the study: N/A Funding: Initiative for Accelerating Regulatory Science in Innovative Drug, Medical Device, and Regenerative Medicine’, and a Grant-in-Aid for Cancer Research from the National Cancer Center to A. H. Disclosure: All authors have declared no conflicts of interest. 34P The expression and functional role of Cripto-1 in human colorectal cancer S. Jun1, H. Karasawa1, T. Suzuki2, S. Nakayama1, M. Katagiri1, S. Maeda1, S. Ohnuma1, F. Motoi1, T. Naitoh1, M. Unno1 1 Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan, 2Department of Pathology & Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan Background: Cripto-1 is located in lipid rafts regions of the plasma membrane binding to a glycosylphosphatidylinositol (GPI) anchor and highly expressed in embryonic stem cells. The expression is very low or absent in the adult tissue, whereas Cripto-1 is reexpressed in a variety of human tumors. However, Cripto-1 expression and its function in colorectal cancer have been investigated in several studies, the relationships between Cripto-1 expression and prognosis have not been adequately assessed in colorectal cancer. This study is aimed to evaluate the clinical and biological significance of Cripto1 in colorectal cancer. Methods: Colorectal cancer specimens were obtained from 192 patients. The Cripto-1 expression was evaluated by immunohistochemistry and clinicopathological features were statistically analyzed. Functions of Cripto-1 were investigated using colorectal cancer cell lines transfected with Cripto-1 siRNA in vitro and Cripto-1 stable knockdown colorectal cancer cell lines in vivo. Results: In clinicopathological analysis, the number of Cripto-1-positive cases was 68 out of 195 (35%) in this study. The Cripto-1 status was significantly associated with tumor size (P < 0.01), depth of invasion (P < 0.01), Lymph node metastasis (P < 0.05), liver metastasis (P < 0.01) and TNM classification (P < 0.01). Moreover, the Cripto-1 status is significantly associated with worse prognosis in colorectal cancer patients (overall survival: P < 0.01, disease free survival: P < 0.01), and multivariate analyses demonstrated that Cripto-1 status was an independent prognostic factor for both overall survival and disease free survival. Subsequent experiments revealed that HT29 and DLD1 colorectal cancer cell lines transfected with siRNA for Cripto-1 reduced proliferation and migration ability in vitro. Furthermore, stable knockdown of Cripto-1 decreased tumor growth in subcutaneous xenograft models (P < 0.01) and lymph node metastasis in orthotopic xenograft models (P < 0.01) Conclusions: These results suggest that Cripto-1 has potential for a prognostic marker and therapeutic target in human colorectal cancer. Legal entity responsible for the study: Tohoku University Graduate School of Medicine Funding: Japan Society for the Promotion of Science Disclosure: All authors have declared no conflicts of interest. 35P Clinical significance of expression of cripto-1 in patients of squamous cell carcinoma of oropharynx M.S. Kumar1, A. Pal2, A. Jain2, S. Ghoshal1, B. Rai1, S. Mohindra3, A. Das4 Radiotherapy, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, 2Biochemistry, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, 3ENT, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, 4 Pathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India 1 Background: Most cancers of head and neck region present in an advanced stage. Early diagnosis of the disease may improve therapeutic outcome by increasing cure rates and decreasing morbidities. A biomarker can detect these tumors at an early stage. Cripto1(CR-1), a teratoma derived growth factor, is overexpressed in certain tumors and Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology found in the plasma of patients. This study was planned to study the over expression and clinical significance of CR-1 in patients with oropharyngeal squamous cell carcinoma(OSCC). The aim of the study is to correlate serum CR-1 levels in patients of OSCC with clinico-pathological features and response to treatment by a) comparing CR-1 levels between patients and controls b) correlating CR-1 levels with histological grade and stage of disease and c) comparing pre and post treatment CR-1 levels and correlate with disease status. Methods: Fifty healthy volunteers(controls) and fifty biopsy proven cases of OSCC were recruited in the study after using inclusion and exclusion criteria. All patients were treated with radical chemo-radiation and response was assessed at 6 weeks post therapy. Serum CR-1 levels were analyzed by ELISA in patients, both before and after treatment, and also in controls. Expression of CR-1 was compared between controls and patients. Pre and post treatment CR-1 levels in patients were compared and correlated with clinic-pathological findings. SPSSv16.0 was used for statistical analysis. Results: As compared to controls, serum CR-1 levels are significantly raised in patients with OSCC (207 pg/ml Vs 497 pg/ml, p¼.003). CR-1 levels are significantly higher in patients with well differentiated and early stage tumors as compared to controls. CR-1 levels decreased significantly after treatment and correspond with response to therapy (497 pg/ml Vs 228 pg/ml, p¼.046). Conclusions: Human serum CR-1 is a potential tumor marker for OSCC. This study also suggests that CR-1 may be useful in early diagnosis of OSCC and merits larger, prospective studies Legal entity responsible for the study: PGIMER, Chandigarh Funding: PGIMER, Chandigarh, India Disclosure: All authors have declared no conflicts of interest. 36P Clinical impact and carcinogenic mechanism of USP3 overexpression in gastric cancer K-Y. Lin Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan Background: Gastric cancer (GC) is one of the most common malignancies in the world, yet little is known about the molecular process of its development and progression. In this study, we investigated the involvement of ubiquitin-specific protease 3 (USP3) in tumor progression, and in the prognosis of human GC. Methods: The patient cohort in this study consisted of 147 GC cases from 1998 to 2005, documenting pathologic and clinical factors, as well as clinical outcomes. Immunohistochemistry and real-time PCR were employed to examine the USP3 expression in 147 pairs of normal and GC tissues and 8 gastric cells. Based on the expression of USP3, one GC cell with high USP3 level was chosen for knockdown of USP3 expression. The effect of USP3 knockdown on the growth and spread of USP3manupulated GC cells was examined. Results: USP3 protein overexpression was observed in 67 patients and was significantly correlated with Lauren classification, depth of invasion, nodal status, distant metastasis, staging, degree of differentiation, vascular invasion, and poor disease-free survival. Multivariate Cox regression analysis showed that USP3 overexpression is an independent prognostic marker for GC. Furthermore, USP3 expression was elevated in several GC cells. In vitro experiments indicated that USP3 knockdown inhibited GC cell growth and spread. Conclusions: This study suggests that overexpression of USP3 can be a useful marker for predicting the outcome of GC patients and that USP3 targeting can represent a potential modality for treating GC. Legal entity responsible for the study: N/A Funding: Ministry of Science and Technology, Taiwan Disclosure: All authors have declared no conflicts of interest. 37P Expression pattern of cyclooxygenase-2 in carcinoma of cervix Methods: This was a hospital based descriptive study conducted in the Department of Pathology, Amala Institute of Medical Sciences, Thrissur over a period of two years. Fifty-one (51) cases of cervical carcinoma were studied which included 7 cases of cervical intraepithelial neoplasias, 42 invasive squamous cell carcinomas, and 1 case of adenocarcinoma. Formalin-fixed paraffin-embedded tissue sections were stained by Hematoxylin and Eosin. Immunohistochemistry for COX-2 were performed on these blocks. Results: COX-2 showed a higher expression pattern in invasive squamous cell carcinoma than in CIN (P ¼ 0.010). One case of adenocarcinoma showed strong positivity and intensity of staining for COX-2 antibody than invasive squamous carcinomas. Among the histopathological correlates, tumor differentiation did not show a positive correlation (P ¼ 0.47). Lymphovascular invasion and lymphnode metastatic were associated with positive COX-2 staining Conclusions: The expression of COX-2 was found to be more in cases of invasive than in CIN. Adenocarcinomas showed a strong expression of COX-2. However, no association of COX-2 expression and the presence of lymphovascular emboli and lymph node metastasis were found in the present study. COX-2 inhibitors need to be studied as a therapeutic adjunct for the treatment of carcinoma cervix. Legal entity responsible for the study: Amala Institute of Medical Sciences Funding: Self Disclosure: All authors have declared no conflicts of interest. 38P M. Bhagat Biochemistry, All India Institute of Medical Sciences, Delhi, India Background: Mena, an actin regulatory gene, was found to be upregulated in several human cancers. Differential splicing of the Mena reports a 19 amino residue after the EVH1 domain producing a Mena invasion isoform (Menainv/Menaþþþ). Hypoxic regions are a predominant feature of growing tumors. In glioma, hypoxia activates multiple signaling pathways leading to angiogenesis and enhanced motility/invasion. These reports and the proposed role of Mena in regulating invasion and metastasis, prompted us to look into the expression pattern of total Mena (Pan Mena) and the INV variant (Mena INV) in gliomas under normoxic (20% O2) and hypoxic (0. 2% O2) conditions. Methods: In order to delineate molecular crosstalk among factors driving glioma progression, we used knockdown and overexpression strategies followed by expression analysis by Q-PCR, immunofluorescence and western blot. Migratory potential of cells was assessed by migration assay. Results: Hypoxic treatment exhibited a significant increase in expression levels of Mena INV in U87MG and A172 (Grade IV) glioma cells. In concordance with Mena INV expression, 0.2% O2 concentration exhibited a maximal effect on migration of glioma cells. On the contrary, hypoxic treatment did not induce Mena INV in Grade II cell lines –SW1088 and Gos-3, while Mena INV variant was totally absent in normal astrocytes. U87MG and A172 when separated into migrated and non-migrated cell populations, a drastic increase in Mena INV expression was observed in the migrated cell population. HIF-2a knockdown and overexpression, and not HIF-1a, affected Mena INV expression in a concomitant manner, indicating the effect of hypoxia on Mena INV via HIF-2a. Finally, significant positive correlation was obtained between HIF-2a and Mena INV in Glioblastoma patient samples. Conclusions: The results indicate a role of Mena INV as a diagnostic marker to assess the migratory potential of transformed cells. We identify hypoxia as one of the reasons leading to increased migratory capabilities in transformed cell. This may increase the efficacy of successful local spread and metastasis, making tumor cells more aggressive. Legal entity responsible for the study: Department of Biotechnology, India Funding: Department of Biotechnology, India and University Grants Commission Disclosure: All authors have declared no conflicts of interest. 39P S. Hameed, V. Nair Pathology, Amala institute of medical sciences, Thrissur, India Background: Cyclooxygenase (COX), the key enzyme required for the conversion of arachidonic acid to prostaglandins was first identified over 20 years ago.In the past decade, however, more progress has been made in understanding the role of cyclooxygenase enzymes in biology and disease than at any other time in history. The most solid, unequivocal and well-established role of COX-2 in the gastrointestinal system is its participation in colon cancer. It has been found that approximately 50% of adenomas and 80-85% of adenocarcinomas show increased expression of COX-2. Cancer of the cervix has been the most important cancer in women in India over the past two decades. Until now, only a few studies has been undertaken to evaluate the role of COX-2 in carcinomas of cervix. This study is undertaken to evaluate the role of COX2 in carcinomas of cervix by studying the expression pattern in different types of carcinomas. Volume 27 | Supplement 9 | December 2016 Mena INV: A prospective bio-marker of glioma under hypoxia Impact of GSTP1 and ABCC4 genes polymorphism on outbreak of cyclophosphamide-based chemotherapy-induced grade 3/4 febrile neutropenia in Iranian breast cancer patients M. Mobaraki1, H. Dehghan Manshadi2, A. Faraji1, M. Zare2, Z. Siavashpour3, M.H. Sanati1 1 Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran, 2Clinical Oncology, Shohadaye 7 Tir, Tehran, Iran, 3 Medical Radiation Engineering, Shahid Beheshti University of Medical Sciences, Tehran, Iran Background: Breast cancer is the most common cancer among women. Cyclophosphamide-based chemotherapy is an effective treatment procedure for breast cancer but some toxicities such as neutropenia are seen to emerge during chemotherapy. GSTP1 and ABCC4 are two significant enzymes that are involved in cyclophosphamide metabolism and transport respectively. doi:10.1093/annonc/mdw574 | ix11 abstracts Methods: In this study, we investigated the impact of two common polymorphisms of GSTP1 (rs1695) and ABCC4 (rs9561778) genes on outbreak of grade 3/4 febrile neutropenia in Iranian breast cancer patients using ARMS-PCR and sequencing methods. Results analysis was done with SPSS Software. Results: Based on statistical analysis, no meaningful association between the abovementioned polymorphisms and outbreak of grade 3/4 febrile neutropenia was observed. But higher frequency of allele A of GSTP1 (rs9561778) and allele G of ABCC4 (rs1695) genes polymorphism in the control group indicate their protective role against outbreak of grade 3/4 febrile neutropenia. Although clinical findings demonstrated statistically meaningful association of cancer stage IIIC (p ¼ 0.037) and existence of other diseases (p ¼ 0.026) in addition to breast cancer with outbreak of grade 3/4 febrile neutropenia. Conclusions: Based on our results, combination of molecular and clinical findings could be useful in prediction of high risk breast cancer patients for outbreak of grade 3/4 febrile neutropenia. Legal entity responsible for the study: Medical Genetics Department of National Institute of Genetic Engineering and Biotechnology, Radiation Oncology Department of shohadaye 7Tir hospital of Iran University of Medical Sciences Funding: Medical Genetics Department of National Institute of Genetic Engineering and Biotechnology, Radiation Oncology Department of shohadaye 7Tir hospital of Iran University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. 40P Effect of ABCB1 and SLC22A16 genes polymorphism in outbreak of doxorubicin-based chemotherapy-induced grade 3/4 febrile neutropenia in Iranian breast cancer patients A. Faraji1, H. Dehghan Manshadi2, M. Mobaraki1, M. Zare2, Z. Siavashpour3, M. Houshmand1 1 Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran, 2Clinical Oncology, Shohadaye 7 Tir, Tehran, Iran, 3Medica Radiation Engineering, Shahid Beheshti University of Medical Sciences, Tehran, Iran Background: Breast cancer is the most common cancer among women worldwide. One of the treatment options for breast cancer is doxorubicin-based chemotherapy but various treatment outcome and toxicities have been observed among different individuals. Neutropenia is one of the common hematologic side effect may be occurred during doxorubicin-based chemotherapy that can be considered as a life threatening factor for the breast cancer patients. ABCB1 and SLC22A16 genes encode two significant proteins that are involved in doxorubicin transportation. Methods: In this study, we explored the effect of two common polymorphisms of ABCB1 (rs10276036) and SLC22A16 (rs12210538) genes in outbreak of grade 3/4 febrile neutropenia in Iranian breast cancer patients using ARMS-PCR and sequencing methods. The results were analyzed by IBM SPSS Statistics software ver. 23. Results: Our results showed no significant association between the mentioned gene polymorphisms with outbreak of grade 3/4 febrile neutropenia. But higher frequency of wild type allele C of ABCB1 (rs10276036) and wild type allele A of SLC22A16 (rs12210538) genes polymorphism in the case group represent their more effect in outbreak of grade 3/4 febrile neutropenia whereas higher frequency of mutant type allele T of ABCB1 (rs10276036) and mutant type allele G of SLC22A16 (rs12210538) genes polymorphism in the control group represent their protective effect in outbreak of grade 3/4 febrile neutropenia. Furthermore, there was a statistical meaningful association between clinical manifestations such as cancer stage IIIC (p: 0.037) and existence of other diseases (p: 0.026) in addition to breast cancer with outbreak of grade 3/4 febrile neutropenia. Conclusions: Our results indicate to evaluate outbreak risk of grade 3/4 neutropenia consideration of molecular and clinical findings could be helpful in screening of high risk breast cancer patients for outbreak of grade 3/4 febrile neutropenia. Legal entity responsible for the study: Medical Genetics Department of National Institute of Genetic Engineering and Biotechnology, Radiation Oncology Department of shohadaye 7Tir hospital of Iran University of Medical Sciences Funding: Medical Genetics Department of National Institute of Genetic Engineering and Biotechnology, Radiation Oncology Department of shohadaye 7Tir hospital of Iran University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. 41P Impact on prognosis of cellular CD 69 expression with CD 38 in Egyptian chronic lymphocytic leukemia M.A. Elbaiomy1, S. Aref2, M. El-Ghonemy2 Medical Oncology, Oncology Center, Mansoura, Egypt, 2Clinical Hematology, Oncology Center, Mansoura, Egypt Annals of Oncology still remains unclear. Several biological parameters have been added to the staging system to stratify those patients. Methods: Our study includes 153 B-CLL patients recruited to Mansoura Oncology Center, in addition to 40 healthy controls matched in age and sex. Cellular CD69 expression was done by multiparameter flowcytometry in addition to routine immunophenotyping pattern of CLL. Results: Patients with high CD69 expression were significantly associated with young age, leukocytosis, advanced Ria stage (III & IV), high B2M serum level and high bcl2 expression, while patients with low CD69 expression were significantly correlated with low CD38 expression. Higher CD69 expression was associated with shorter PFS (median, 16 months vs. 30 months; P ¼ 0.001) and shorter OS (median, 20 months vs. 34 months; P 0.001). Patients with high CD38 expression were significantly associated with old age, leukocytosis, advanced Ria stage (III & IV), high B2M serum level and high bcl2 expression. Higher CD38 expression was associated with shorter PFS (median, 22 months vs. 30 months; P ¼ 0.006) and shorter OS (median, 28 months vs. 34 months; P ¼ 0.007). Combined high expression of both markers showed poor PFS (median, 14 months vs. 30 months in combined low expression; P ¼ 0.002) also, combined high expression of both markers showed poor OS (median, 19 months vs. 34 months in combined low expression; P ¼ 0.005). There was no biological effect of chemotherapy on PFS, OS. Cox proportional hazard regression showed that high CD69 expression was an independent prognostic factor for poor PFS (P ¼ 0.01) along with high CD38 expression (P ¼ 0.05). Also, high CD69 expression was an independent prognostic factor for poor OS (P ¼ 0.016) along with high CD38 expression (P ¼ 0.057). Conclusions: CD69 and CD38 over expression predict adverse outcome and both could be applied in the scoring system of CLL as simple and easily applicable to stratify early progressive patients and so enabling timely therapeutic decisions to improve outcome. Legal entity responsible for the study: OCMU Funding: OCMU Disclosure: All authors have declared no conflicts of interest. 42P Promoter hypermethylation of BRCA1, DAPK1 and RASSF1A is associated with increase mortality among breast cancer patients P. Yadav1, M. Mirza1, K. Nandi1, R.C. Kaza2, S.K. Jain2, A. Saxena1 Department of Biochemistry, Maulana Azad Medical College New Delhi A.L.N. Hospital, New Delhi, India, 2Department of Surgery, Maulana Azad Medical College New Delhi A.L.N. Hospital, New Delhi, India 1 Background: Promoter hypermethylation has been seen in several genes in cancer development and progression. Hypermethylation-derived silencing of different tumor suppressor genes (TSGs) has been observed to be associated with breast cancer pathogenesis. The current study was aimed to evaluate the role of TSGs (BRCA1, DAPK1 and RASSF1A) promoter hyermethylation in breast cancer and their correlation with clinico-pathological features of breast cancer patients. Methods: Promoter hypermethylation status of BRCA1, DAPK1 and RASSF1A was observed in mononuclear cells (MNCs) DNA extracted from peripheral blood samples of 60 histopathologically confirmed newly diagnosed, untreated cases of breast cancer as well as 60 age and sex matched healthy controls by using MS-PCR. Total follow up period was 45 months and mean follow up time was 30.98 months. The association of promoter methylation and breast cancer specific mortality was analyzed by Coxproportional hazards models. Kaplan-Meier survival analysis was performed for overall survival of breast cancer patients. The study was ethically approved by Institutional Ethics Committee, Maulana Azad Medical College, New Delhi. Results: A significant association was seen between BRCA1, DAPK1 and RASSF1A promoter hypermethylation (51.66% (P < 0.001), 55% (P < 0.001), 46.6% (P < 0.001) respectively) in breast cancer patients compared to healthy controls. We have seen a strong correlation between BRCA1 (P ¼ 0.009), DAPK1 (P ¼ 0.008) and RASSF1A (P ¼ 0.02) promoter hypermethylation with early and advanced stage of breast cancer. We have observed that breast cancer-specific mortality was significantly associated with promoter hypermethylation of BRCA1 [HR & 95% CI: 3.25(1.448-7.317)] and DAPK1 [HR & 95% CI: 2.32(1.05-5.11)], while the association with RASSF1A promoter hypermethylation was less associated [HR and 95% CI: 1.54(0.697-3.413]. Additionally, a significant association was seen between promoter hypermethylation of BRCA1 (P ¼ 0.004) and DAPK1 (P ¼ 0.03) with poor overall survival of breast cancer patients. Conclusions: Our results suggest that promoter hypermethylation of TSGs may be a potential new biomarker of breast cancer prognosis. A large pool study will be required to confirm these findings. Legal entity responsible for the study: Dr. Alapna Saxena, Mr. Prasant Yadav Funding: Maulana Azad Medical College Disclosure: All authors have declared no conflicts of interest. 1 Background: Clinical variability in chronic lymphocytic leukemia with progress from indolent, with no need of treatment, to aggressive, with short morbidity and survival, ix12 | abstracts Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology 43P Integrated analysis of genome-wide DNA methylation and gene expression profiles identifies potential novel biomarkers of rectal cancer G. Li, J. Wei, S. Dang, Y. Zhou, X. Li, H. Chen, M. Liu Department of General Surgery, Fourth Hospital of Harbin Medical University, Harbin, China Background: DNA methylation was regarded as the promising biomarker for rectal cancer diagnosis. However, the optimal methylation biomarkers with ideal diagnostic performance for rectal cancer are still limited. This study was aimed to identify new molecular markers for rectal cancer. Methods: We mapped DNA methylation and transcriptomic profiles in the six rectal cancer and paired normal samples. Further analysis revealed the hypermethylated probes in cancer prone to be located in gene promoter. Results: Transcriptome analysis presented 773 low-expressed and 1,161 over-expressed genes in rectal cancer. Correction analysis identified a panel of 36 genes with an inverse correlation between methylation and gene expression levels, including 10 known colorectal cancer related genes. From the other 26 novel mark genes, GFRA1 and GSTM2 were selected for further analysis on the basis of their biological functions. Further experiment analysis confirmed their methylation and expression status in a larger number (44) of rectal cancer samples, and ROC curves showed higher AUC than SEPT9, which has been used as a biomarker in rectal cancer. Conclusions: Our data suggests that aberrant DNA methylation of contiguous CpG sites in methylation array may be potential prognostic markers of rectal cancer. Legal entity responsible for the study: Ming Liu Funding: National Natural Science Foundation of China Grant number: 81372612, 81302059 Disclosure: All authors have declared no conflicts of interest. 44P 45P MiR-183 is frequenty methylated and related to poor survival in human hepatocellular carcinoma S.L. Anwar1, B. Hasemeier2, E. Schipper2, B. Skawran3, U. Lehmann2 Surgery, Gadjah Mada University/Dr. Sardjito General Hospital, Yogyakarta, Indonesia, 2Pathology, Hannover Medical School, Hannover, Germany, 3 Molecular Pathology, Hannover Medical School, Hannover, Germany 1 Background: Epigenetic silencing of microRNA genes has been shown to contribute substantially in carcinogenesis including heparocellular carcinoma (HCC), the fifth most common cancer and the third leading cause of cancer mortality worldwide. Methods: Using DNMT knockdown and microRNA microarray profiling in HCC cell lines, we then perform DNA methylation and microRNA expression analysis in primary HCC tumor samples. Results: Using DNMT knockdown and microRNA profiling in HCC cell lines, we found that hsa-mir-183 is upregulated after the knockdown and confirmed this with qRT-PCR. Further analysis in primary HCC specimens showed that miR-183 is hypermethylated in 30% of HCC (n ¼ 40). Expression of mature miR-183 showed an inverse correlation with the methylation levels. In HCC cells, DNMT knockdown and 5-aza-2’-deoxycytidine treatment reduced methylation and stimulated expression of miR-183. In HCC patients, hypermethylation at miR-183 promoter significantly correlates with poor survival (log rank test p ¼ 0.03). DNA methylation analysis in healthy liver, benign liver tumors (HCA and FNH) showed absent of hypermethylation suggesting that aberrant miR-183 methylation is specific event in liver malignancy. Conclusions: Our data indicate that hypermethylation in miR-183 is a frequent event in HCC and potentially useful as a new diagnostic and prognostic marker. Legal entity responsible for the study: Department of Surgery Faculty of Medicine Universitas Gadjah Mada Hannover Medical School Funding: DFG German Science Foundation Disclosure: All authors have declared no conflicts of interest. Pharmacogenetic methods of personalization in medical treatment of colon cancer J. Ibragimov, D. Pulatov, S. Kamishov, S. Abdujabbarov Chemotherapy2, National Cancer Research Center of Uzbekistan, Tashkent, Uzbekistan Background: The importance of colon cancer (CC) increases due to the steady growth of morbidity and mortality from this disease in developed countries. According to the WHO, there are worldwide 600,000 new cases of CC yearly with half of them dying. This study aimed to improve the results of choosing personalized chemotherapy (CT) treatments by studying the molecular-genetic parameters of patients with CC. Methods: We investigated samples of blood tests for gene polymorphisms XPD and DPYD_D949V, DPYD_14 in 75 patients with CC, who were treated at the departments of chemotherapy National Cancer Research Center of Uzbekistan in the period 20142016. The study included patients previously treated with several courses of CT containing 5-fluorouracil and platinum-based drugs and have acquired resistance to those regimens. Of the 75 patients: 35 women, 40 men. The median age was 39 6 1. Patients with histological established mainly adenocarcinoma G2. Under the conditions of genetic laboratories we studied different variants of polymorphism alleles associated with the repair activity of the gene XPD. Results: The presence Lys751Gln polymorphism, Asp312Asn alleles in the XPD gene was found in 32 (43%) and 25 (33.3%) patients, respectively. Mutations in the genes DPYD_D949V, DPYD_14 were found in 29 (38.6%) patients from 75. As a result of the processing of retrospective data it was shown that in patients bearing polymorphisms and mutations in these genes the positive response to the therapy did not exceed 5%, and the relative risk of death among patients with mutant alleles was increased by 1.8 times (P ¼ 0.030). Conclusions: Thus, polymorphisms Lys751Gln, Asp312Asn XPD gene and gene DPYD is an important prognostic factor in the clinical application of CT with platinum drugs and 5-fluorouracil. The study of these factors can prevent inappropriate use of the different regimens of CT in the treatment of CC. Considering the pronounced incidence in certain groups of patients, these figures are subject to further additional study, and therefore a further study considering the toxicity of treatment, overall survival, and duration of the period without relapse is ongoing. Legal entity responsible for the study: National Cancer Research Center of Uzbekistan Funding: Health Ministry of Uzbekistan Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 46P Identification of novel biomarkers distinguishing pancreatic head cancer from distal cholangiocarcinoma discovered by proteomics analysis T. Takenami, S. Maeda, H. Karasawa, Y. Mochizuki, T. Aizawa, S. Jun, H. Musha, T. Morikawa, K. Nakagawa, H. Hayashi, F. Motoi, T. Naitoh, M. Unno Department of Surgery, Tohoku University Hospital, Sendai, Japan Background: Pancreatic cancer and cholangiocarcinoma are the most aggressive cancer types with dismal prognosis. New combination chemotherapy, such as nab-paclitaxal plus gemcitabine, FOLFIRINOX for pancreatic cancer and cisplatin plus gemcitabine for cholangiocarcinoma, have improved progression-free survival and overall survival in patients with unresectable locally advanced or metastatic cancer. However, it is often difficult to distinguish pancreatic head cancer from distal cholangiocarcinoma, because of their histological and anatomical similarity. This study aims to identify novel protein biomarkers to distinguish these lethal cancers, using proteomic analysis of laser microdissected (LMD) formalin-fixed paraffin embedded tissue (FFPE). Methods: Ten cases of pancreatic head cancer and 8 of distal cholangiocarcinoma were analyzed. Cancerous cells collected from FFPE tissue sections by LMD were processed for liquid chromatography tandem MS (LC-MS/MS). Candidate proteins were identified by semi-quantitative comparison so-called spectral counting analysis and also chosen based on the nonparametric G-test with statistical significance as indicated by p < 0.01. Results: Consequently, 1,361 proteins were detected in pancreatic head cancer and 1,274 proteins in distal cholangiocarcinoma. In total, 1,820 proteins were detected from 18 samples. The detected proteins were semi-quantitatively compared and statistically analyzed by G-test with a significant difference. We identified 6 proteins were overexpressed in pancreatic head cancer groups and 12 proteins in distal cholangiocarcinoma groups, respectively. Conclusions: We identified 18 candidate protein biomarkers for distinguishing pancreatic head cancer from distal cholangiocarcinoma using proteomic analysis. Legal entity responsible for the study: Tohoku University Funding: Japan Society for the Promotion of Science Disclosure: All authors have declared no conflicts of interest. doi:10.1093/annonc/mdw574 | ix13 abstracts 47P Loss-of-function PTPRT and PTPRD mutations predict bevacizumab resistance in metastatic colorectal cancer patients K.T. Tan1, S-J. Chen1, H-C. Chen1, H. Hung-Chih2 Clinical Sequencing, ACT Genomics Co. Ltd., Taipei, Taiwan, 2Division of Hematology-Oncology, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan 1 Background: Bevacizumab is a VEGF-directed anti-angiogenic therapy for KRASmutated metastatic colorectal cancer (mCRC) patients. However, some patients do not benefit from the treatment and there is no appropriate biomarker for the response prediction The aim of this study was to identify genetic markers that might predict the response to bevacizumab treatment. Methods: 34 archived primary tumor tissues of stage IV mCRC cancer were analyzed, including 17 bevacizumab responders and 17 non-responders. We assessed all coding exons in 409 cancer-related genes for base substitutions, indels, and copy number alterations. The average sequencing depth was > 1,000. Results: We observed 414 genomic alterations in 194 genes in all tumors (mean 12.1, range 6-19). The average number of genomic alterations was similar in responder (12.1 range 3-18) and non-responders (12.2, range 7-19) tumors. The most commonly mutated in both groups genes were TP53, APC, SYNE1 and PTPRT. Pathway analyses of altered genes revealed aberration in p53, Wnt, and JAK/STAT in both groups. Up to 35% of mCRC patients harbor mutations or copy number alterations in the PTPRT or PTPRD, protein tyrosine phosphatases in the JAK/STAT pathway. Interestingly, lossof-function mutation or copy number loss of PTPRT/PTPRD were found to be enriched in the bevacizumab resistance tumors (p ¼ 0.0072). Conclusions: Our data suggest that PTPRT and PTPRD loss-of-function alterations may serve as a predictive biomarker of sensitivity to bevacizumab treatment in mCRCs. Legal entity responsible for the study: The study was funded by a biotech company Funding: ACT Genomics Disclosure: All authors have declared no conflicts of interest. 48P Annals of Oncology Inhibition of LAP2a can suppress cell aggressiveness in breast cancer X. Li1, Y. Huang2, Y. Hu3 Medical Oncology, 2nd Affiliated Hospital of Zhejiang University University School of Medicine, Hangzhou, China, 2Cancer Institute, 2nd Affiliated Hospital of Zhejiang University University School of Medicine, Hangzhou, China, 3 Surgical Oncology, 2nd Affiliated Hospital of Zhejiang University University School of Medicine, Hangzhou, China 1 Background: Breast cancer is the most common malignancy in women worldwide. But to date, there is no good serum protein marker for breast cancer diagnosis and prognosis. We conducted this study to screen and identify specific protein markers of breast cancer. Methods: Mass spectrometry was applied to screen and identify differential serum protein profiles between 63 breast cancer patients and 40 healthy controls. Immunohistochemistry (IHC) and western blot analysis were used as verification experiments. Biological functions of candidate protein marker were studied in vitro. Results: Two amino acid fragments with sizes of 3.9kDa and 5.6kDa, respectively, were detected as candidate markers. A combined diagnostic model composed of these two fragments was built, with a sensitivity of 82.3% and a specificity of 95.3%. The 5.6kDa fragment, which was up regulated in breast cancer, was an important segment of lamina-associated polypeptide 2 alpha (LAP2a). IHC and western blot experiments confirmed over expression of LAP2a in breast cancer tissues. An inhibition plasmid vector of LAP2a-small hairpin RNA (shRNA) was constructed and transfected into MCF-7 cells. CCK-8 experiments on transfected cells showed that inhibition of LAP2acould not influent cell proliferation. Transwell and matrigel-transwell assays indicated that inhibition of LAP2a could significantly reduce cell migration and invasion abilities. Conclusions: We built a diagnostic model for early detection of breast cancer with a satisfactory accuracy. LAP2awas identified as a candidate serum protein marker, which was overexpressed in breast cancer. Inhibition of LAP2acould suppress MCF-7 cell aggressiveness. Our study indicated that LAP2acould be a potential serum biomarker and therapeutic target of breast cancer. Legal entity responsible for the study: The Second Affiliated Hospital, Zhejiang University School of Medicine, China Funding: Zhejiang Provincial Natural Science Foundation of China Disclosure: All authors have declared no conflicts of interest. ix14 | abstracts 49P The role of circulating cell-free DNA measured by a simple fluorescent assay to predict relapse in triple negative breast cancer receiving neoadjuvant chemotherapy K. Park1, M. Woo2, J.E. Kim3, J-H. Ahn4, K.H. Jung4, S.B. Kim2 Medical Oncology and Hematology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea, 2Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 3Oncololy, Asan Medical Center, Seoul, Republic of Korea, 4Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea 1 Background: Prior technique to measure cell free DNA(CFD) is labor-intensive and expensive, while, recently developed fluorescent CFD assay is more simple and convenient. The aim of this study was to evaluate the role of CFD measured by a fluorescent assay as a biomarker of patients with triple negative breast cancer (TNBC) received neoadjuvant chemotherapy Methods: This study is a biomarker substudy of prospective observational study (NCT02001519, NCT02001506). We prospectively enrolled patients with TNBC, clinical stage II or III (T > 1.5cm or lymph node > 1.5cm), who were scheduled for neoadjuvant chemotherapy. Patients received 4 cycles of adriamycin 60 mg/m2 plus cyclophosphamide 600 mg/m2 (AC) followed by 4 cycles of cisplatin or docetaxel, and surgery. Plasma samples were obtained from patients before initial chemotherapy (baseline-CFD) and after 4 cycles of AC neoadjuvant chemotherapy (AC-CFD). Results: This study included 72 patients who met the inclusion criteria. The mean levels of baseline-CFD and AC-CFD were 239668 ng/mL and 210666 ng/mL, respectively, and the CFD level was significantly decreased after AC chemotherapy. (p ¼ 0.001) The baseline-CFD was not associated with initial tumor characteristics. (T stage 1-2 vs. 3, p ¼ 0.313; N stage 0 vs. 1-3, p ¼ 0.317) There was no statistically significant difference between patients with response (CR or PR) to AC chemotherapy and those without response in terms of baseline-CFD, AC-CFD, and change of CFD between two values. (p ¼ 0.814, p ¼ 0.839, p ¼ 0.927) With 33.6 months of median follow up, there were 18 cases of relapse. Relapsed group showed numerically higher level of baseline-CFD, although it was not statistically significant. (relapse, 259 ng/mL; non-relapse, 233 ng/ mL; p ¼ 0.161) We performed a ROC curve analysis of baseline-CFD for relapse, and found an area under the curve of 0.62 (95% CI, 0.46-0.78) at 222 ng/mL. Patients with baseline-CFD above 222 showed higher relapses than those below 222. (HR, 2.75; 95% CI, 0.96-7.84; p ¼ 0.059) Conclusions: The baseline-CFD obtained using a simple and convenient fluorescent assay could predict relapse, suggesting baseline-CFD as a potential biomarker for risk stratification of TNBC. Clinical trial indentification: A biomarker substudy of prospective observational study (NCT02001519, NCT02001506) Legal entity responsible for the study: The study was approved by the institutional review board of Asan Medical Center and conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines Funding: N/A Disclosure: All authors have declared no conflicts of interest. 50P Droplet digital PCR measurement of c-Met gene amplification in plasma cell free DNA in patients with advanced NSCLC H-F. Gao, X. Zhang, J-J. Yang, Y-L. Wu Lung cancer, Guangdong General Hospital, Guangzhou, China Background: Advanced NSCLC patients with c-Met amplification can respond to cMet inhibitors. Unfortunately, the lack of adequate tissue often precludes c-Met testing. We hypothesized that plasma cell-free DNA (cfDNA) can offer an alternative source of biologic material for testing. Methods: We designed a target region on exon 4 of c-Met gene, used RNaseP as the reference gene. We evaluated this c-Met:RNaseP ddPCR assay to determinate c-Met amplification in plasma cfDNA in 34 patients with advanced NSCLC who received cMet inhibitor therapy, results were correlated with clinical findings. Results: The concordance rate of ddPCR with FISH was not high (55.9%); however, patients who were c-Met-positive by ddPCR had significantly longer PFS after c-Met inhibitor therapy compared with c-Met-negative patients (4.352 months and 1.657 months, respectively, P ¼ 0.008). Conclusions: Our results demonstrated that this ddPCR method can be used to evaluate c-Met status in plasma cfDNA samples. The c-Met status determined in cfDNA may have potential as a predictive factor for PFS after c-Met inhibitor therapy. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology 51P Clinical feasibility of EGFR mutation detection by CastPCR in plasma cell-free DNA of lung adenocarcinoma patients Y. Yang, Z. Hang, S. Xiaoyan, Y. Lixia, L. Baorui, W. Lifeng The Comprehensive Cancer Center of Drum-Tower Hospital., Affiliated Drum Tower Hospital Nanjing University, Nanjing, China Background: CastPCR is a newly developed gene analysis assay with high sensitivity and specificity. Multiple studies have demonstrated that CastPCR is superior in gene analysis of tumor tissue compared with other assays such as Sanger sequencing and ARMS. In previous experiments, we have identified the sensitivity of CastPCR in detection of EGFR mutation-known lung cancer cell lines mimicing that of peripheral blood: 0.1% in exon 19 deletion (Del19), L858R in exon 21 and 1% in T790M in exon 20. Since there is difficulty in obtaining tumor tissue from late-staged lung cancer patients and the infeasibility of repeated biopsy and dynamic monitoring during targeted therapy, a complementary method is badly needed. Methods: 107 FFPE tissue samples of treatment-naive lung adenocarcinoma patients and matched peripheral blood were collected. CastPCR was used to analysis the EGFR mutation status (exon 19 del2235-2249, del2236-2250, exon 20 T790M and exon 21 L858R) both in the FFPE samples and the peripheral blood. Feasibility-identifying parameters including sensitivity, specificity, positive predictive value, negative predictive value and the concordance was calculated, respectively. Results: 1. In FFPE samples, 51.4% (55/107) were EGFR mutation-positive: 37.4% (40/ 107) harbored EGFR sensitizing mutations (Del 19 or/and L858R) and 18.7% (20/107) harbored EGFR resistant mutations (T790M), and 5.6% (6/107) harbored double mutations in the same sample. 2. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the concordance of EGFR mutation detection in cfDNA by CastPCR was shown in the table. Table: 51P Parameters of mutation analysis Parameters Sensitivity Specificity PPV NPV Concordance EGFR T790M 19Del & L858R 56.4% (31/55) 94.2% (49/52) 91.2% (31/34) 67.1% (49/73) 74.8% (80/107) 45.0% (9/20) 100.0% (87/87) 100.0% (9/9) 88.8% (87/98) 89.7% (96/107) 57.5% (23/40) 95.5% (64/67) 88.5% (23/26) 79.0% (64/81) 81.3% (87/107) PPV: Positive Predictive Value; NPV: Negative Predictive Value Conclusions: CastPCR can not only effectively detect the EGFR mutation statues in tumor FFPE samples, but also can confer clinical feasibility of EGFR mutation analysis in cfDNA. Legal entity responsible for the study: Lifeng Wang Funding: 1. the Health Scientific Research Project of Jiangsu Province, Nanjing, China (grant no. H201235); 2. Key Project of Nanjing Medical Science and Technology Development Foundation, Nanjing, China (grant no. ZKX12012). Disclosure: All authors have declared no conflicts of interest. 52P Expression of CT antigens in periampullary carcinomas patients: Potential minimally-invasive biomarkers for diagnosis positive Sp17 protein expression also found to have increased levels of circulating antiSp17 antibody levels. Conclusions: In the present study, increased expression of all the CTA genes was observed in both tissues and sera of PAC patients emphasizing its diagnostic potential. Moreover, elevated circulating levels of anti-Sp-17 and NY-ESO-1 antibodies were observed in serum of PAC patients with good sensitivity and specificity and could discriminate these patients from healthy individuals. In addition to these, expression of Sp17 protein in PAC tissues confirms the high circulating levels of anti-Sp17 antibody in serum of PAC patients. Legal entity responsible for the study: Dr Rinu Sharma (Principal Investigator) Funding: Department of Science of Technology, India Disclosure: All authors have declared no conflicts of interest. 53P T. Nagasaka, A. Nyuya, T. Toshima, T. Kawai, K. Yasui, K. Kimura, Y. Mori, Y. Umeda, H. Kishimoto, T. Fujiwara Gastroenterological Surgery, Okayama University Hospital, Okayama, Japan Background: In spite of the encouraging findings from the National Lung Screening Trial, there is still an ongoing debate on the cost-benefit profile of low-dose computed tomography for lung cancer screening. Consequently, development of complementary biomarkers with less invasive and higher accuracy for lung cancer detection will alleviate this important clinical requirement. To conquer this requirement, we tried to develop a non-invasive, high-throughput DNA methylation-based screening test using sputum to screen subjects with lung cancer burden. Methods: We have previously reported a unique and highly sensitive assay that uses a single-step bisulfite modification of DNA, followed by fluorescence-based PCR to measure DNA methylation (fluoresence-HiSA) to analyze methylation of 8 loci in 4 genes in R technology sputum specimens. In this study, we developed a new assay by using LuminexV (Luminex-Hi-SA) which can anticipate methylation status in 52 CpG sites in the 8 loci. By using two procedures, we analyzed 207 sputum samples from patients intended for resection of lung tumors, and subjects without any lesion detected by high dose computed tomography. All sputum specimens were collected before surgical resection, with complete clinical annotation, including 89 adenocarcinoma, 25 squamous cell carcinoma, 3 small cell carcinoma, 4 large cell carcinoma, 13 metastatic lung carcinoma, 5 other malignant carcinoma, and 68 subjects without any malignant lesions. Results: Our assays successfully identified two or more methylated markers in sputum collected on replicate analysis from 58.3% of malignant patients and 14.7% of subjects without any malignant lesions (AUC ¼ 0.75317) by fluoresence-HiSA. To our surprise, Luminex-Hi-SA improved the accuracy for the detection of subjects with lung cancer burden (AUC¼0.94399). Conclusions: Our novel, non-invasive, DNA methylation-based screening test using R technology can robustly detect a variety of lung cancers. sputum by using LuminexV Our modified DNA methylation assay for sputum provides an effective and promising tool for the non-invasive screening for lung cancers, highlighting its clinical utility in reducing the mortality and morbidity associated with lung cancers. Legal entity responsible for the study: N/A Funding: KAKENHI Disclosure: All authors have declared no conflicts of interest. S. Singh1, A. Saraya2, R. Sharma1 Biotechnology, Guru Gobind Singh Indraprastha University, Delhi, India, 2 Gastroenterology, All India Institute of Medical Sciences, Delhi, India 54P 1 Background: Detection of periampullary carcinoma (PAC) by modern diagnostic techniques is less promising. Cancer Testis Antigens (CTAs) are found to be expressed by normal germ cells only. Recent studies showed aberrant expression of certain CTAs viz. Sp17, NY-ESO-1, SCP1 and GAGE in various cancers. However, their expression have not yet been analysed in PAC. Methods: Real time PCR was done to assess the mRNA expression of Sp17, NY-ESO-1, SCP1 and GAGE in tissues and sera samples collected from consented PAC patients and normal subjects. Moreover, circulating levels of anti-Sp17 and NY-ESO-1 antibodies were determined in sera of PAC patients and normal subjects using ELISA. Immunohistochemical analysis of Sp17 protein in PAC tissues was also carried out. Results: Significantly increased mRNA expression of Sp17, NY-ESO-1, SCP1 and GAGE was found in 70%, 75%, 80% and 70%, respectively, PAC tissues when compared with distant matched non-malignant tissues (P < 0.05). A significant and positive correlation was found between Sp17 and GAGE gene expression (r ¼ 0.524; P ¼ 0.018) and SCP1 and GAGE gene expression (r ¼ 0.764; P < 0.001) in tumor tissues. Similarly, significantly increased levels of these mRNAs were also demonstrated in sera of PAC patients (P < 0.05). Circulating levels of anti-Sp17 and NY-ESO-1 antibodies were found to be significantly elevated in 89% and 74% PAC patients, respectively (P < 0.001). Area under curve for Sp17 and NY-ESO-1 ELISA was 0.958 and 0.896, respectively. Furthermore, all the neoplastic and preneoplastic tissue samples showing Volume 27 | Supplement 9 | December 2016 Update results of a novel assay for the detection of methylated CpGs from sputum to screen patients with lung cancer Circulating prostate-specific antigen and telomere length in a nationally representative sample of men without history of prostate cancer W. Wulaningsih1, Y. Astuti2, T. Matsuguchi3, P. Anggriyadanny4, J. Watkins5 MRC Unit for Lifelong Health and Ageing, UCL - University College London, London, UK, 2Surgery & Cancer, Imperial College London - Hammersmith Hospital, London, UK, 3Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA, 4Division of Hematology/ Oncology, Gadjah Mada University/Dr. Sardjito General Hospital, Yogyakarta, Indonesia, 5Division of Cancer Studies, King’s College London Guy’s Hospital, London, UK 1 Background: We investigated the association of prostate-specific antigen (PSA) with leukocyte telomere length, which may be altered in preclinical prostate malignancies. Methods: This study was based on the 2001-2002 USA National Health and Nutrition Examination Survey (NHANES). A subsample of 1,127 men aged 40-85 years without prior history of prostate cancer who provided informed consent and blood samples were selected. Leukocyte telomere length (LTL) relative to standard DNA reference (T/S ratio) was quantified by polymerase chain reaction (PCR). Survey-weighted multivariable linear regression was performed to examine T/S ratio across quintiles of total and free PSA and free-to-total PSA ratio (%fPSA). A sensitivity analysis was performed by excluding men dying from prostate cancer during follow-up through to 31 December 2006. Stratification analyses were carried out to assess any effect doi:10.1093/annonc/mdw574 | ix15 abstracts Annals of Oncology modification by age group, race, body mass index (BMI) and levels of C-reactive protein (CRP), a marker of inflammation. Results: Higher total PSA levels were associated to longer LTL, with approximately 8% increase in log-transformed T/S ratio (95% confidence interval [CI]: 2-13%) among men in the highest quintile of total PSA compared to the lowest in the fully adjusted model (Ptrend¼0.01). No significant association was found for free PSA or %fPSA, although nonlinearity between all PSA measures and T/S ratio was indicated. Similar results were found after excluding men who died from prostate cancer during follow-up. We also found the associations between total PSA and T/S ratio to be strongest among non-Hispanic blacks, non-obese men (BMI <30 kg/m2), and those with low CRP. However, a significant interaction was only found between total PSA and race/ethnicity (Pinteraction¼0.01). Conclusions: Total PSA levels were strongly associated to leukocyte telomere length, particularly among non-Hispanic blacks. Our findings support a potential link between PSA and specific mechanisms contributing to prostate cancer development. Legal entity responsible for the study: King’s College London Funding: PILAR Research and Education Foundation Disclosure: All authors have declared no conflicts of interest. 55P CTC count & gene expression profiling among Filipino NSCLC H.G. Luna, G. Cristal-Luna Internal Medicine, Section of Medical Oncology, National Kidney and Transplant Institute, Quezon City, Philippines Background: CTC count with gene expression profiling’s prognostic value has been documented in mBRCA, mPC & mCRC. Presently, there is a challenge in understanding its prognostic value among Filipino NSCLC patients. This study aims to describe first data on Filipino NSCLC CTC count & gene expression profile. Methods: Charts of mNSCLC patients who underwent procedure from Jan 2014 to Jan 2016 were reviewed. CTC count was done using EpCam-targeted magnetic beads on blood extracts then immunofluorescence of cell surface markers (DAPIþ CD45- CKþ). Gene expression profiling through RT PCR of buffy coat RNA extracts was done using 3 tumor asso-genes (CD133 CK19 MUC1). Demographics, histo, EGFR mutation, available CTC count & gene expression profiling, treatment, objective response after 3 treatment cycles & TTP were described. Results: 12 NSCLC were analyzed. 66% were male, 62þ/- 10 years. 75% Adeno & 25% Sq. 50% EGFR MT, 42% EGFR WT, 8% unknown EGFR status. Baseline CTC count ranged from 0-3 (mean:0.91). Post tx CTC count ranged 0-2 (mean: 0.66) in 6 subjects. 12 subjects with baseline gene expressions showed CD133 upregulated in 50%, KRT19 upregulated in 33% & MUC1 upregulated in 66%. EGFR MT adeno (n ¼ 5) received chemo followed by TKI in 60% (CR 33% PR 33% PD 33% TTP 66% NR) & TKI only in 40% (CR 50% SD 50% TTP 50% NR). EGFR MT Sq (n ¼ 1) received chemo (CR 100% TTP NR). Among EGFR WT (Ad n ¼ 3, Sq ¼ 2), all received chemo (PR 60% SD 20% PD 20% TTP 80% NR). 100% of unknown EGFR received chemo was in CR. 2/3 with post tx gene expression showed 44% change in expression, n ¼ 4/9. 56P Single circulating tumor cells RNA profiling by label-free enrichment and active single cell selection on an integrated fluidic system Y.F. Lee1, N. Ramalingam2, L. Szpankowski2, A. Leyrat2, N.D. Angeles2, A. Wu1, J. West2, A.A. Bhagat1 1 Research, Clearbridge BioMedics, Singapore, 2Research, Fluidigm Corporation, San Francisco, CA, USA Background: Circulating tumor cells (CTCs) are disseminated tumor cells from the primary tumor into the circulatory system and are potentially “seeds of metastasis” that may initiate a secondary tumor. In spite of its biological relevance, the role of CTCs in promoting metastasis and tumor evolution remains elusive. In order to gain insights in the mechanism of circulating tumor cells survival and metastasis, we study single CTC pre-enriched using a size-based enrichment method and further singly isolated into reaction chambers by a microfluidic integrated chip for RNA sequencing (RNA-Seq). Methods: CTCs from 7.5 ml of peripheral blood sample from breast cancer patients R , a label- free spiral microfluidics- based system that were enriched using ClearCell FX V enriches for larger cells. To differentiate larger blood cells from putative CTCs, we stained the enriched cells with Alexa 647- conjugated CD45 and CD31 to identify leukocytes and endothelial cells respectively. Calcein AM (live cell marker) and CellTrackerTM Orange (universal cell marker) were added to identify live cells. Singly R ) system which integrates selection of CTCs was done using PolarisTM (FluidigmV fluorescence imaging, image based- cell selection and compartmentalization of cells for downstream mRNA chemistry. Full-length cDNA were generated from Polaris and the quality was checked using Bioanalyzer. Sequencing libraries were synthesized using Nextera kit and sequenced with Illumina MiSeq/NextSeq. Results: Good quality cDNA were generated from single CTCs. Sequenced data showed high quality sequencing, with read depth of up to 2.5 million reads, with low percentage of mapped reads to ribosomal RNA and mitochondrial RNA. Unsupervised hierarchal clustering of gene expression data showed clustering by patient, but considerable heterogeneity was also observed among the CTCs from the same patient. Conclusions: Here, we present the feasibility of integrating two microfluidics platforms to capture single CTC for transcriptome study. Preliminary analysis of our data suggests that the heterogeneity of tumor sample can be elucidated from single cell RNA-seq of CTCs. Legal entity responsible for the study: Clearbridge BioMedics; Fluidigm Corporation Funding: Clearbridge BioMedics, Fluidigm Corporation Disclosure: Y.F. Lee, A. Wu, A.A. Bhagat: Author is an employee of Clearbridge BioMedics. N. Ramalingam, L. Szpankowski, A. Leyrat, N.D. Angeles, J. West: Author is an employee of Fluidigm Corporation. 57P Inter-observer variability in programmed death-ligand 1 (PD-L1) immunohistochemistry scoring in non small cell lung cancer (NSCLC) A. Thai1, G. Rivalland1, K. Asadi2, C. Murone3, T. John4, P. Mitchell1 Medical Oncology, Austin Hospital, Heidelberg, VIC, Australia, 2Anatomical Pathology, Austin Hospital, Heidelberg, VIC, Australia, 3Victorian Cancer Biobank, Austin Hospital, Heidelberg, VIC, Australia, 4Medical Oncology, Austin Helath/Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia 1 Table: 55P NSCLC CTC count & gene expression pre & post tx Baseline Post Tx Histo EGFR CTC CD133 KRT19 MUC1 CTC CD133 KRT19 MUC1 Tx OR TTP A S A MT MT WT 0 0 1 U N U N N N U D U 2 0 1 U U N N N N U N N CT CR NR C CR NR C SD NR A-Adeno S-Sq U-upregulated N-negative D-downregulated NR-not reached Conclusions: NSCLC is an aggressive disease despite Filipino CTC count ranging from 0-3. However, upregulation in at least one baseline gene among subjects was noted in 75% of cases, while 41% showed upregulation in 2 baseline genes (CD133 and MUC1). Post treatment gene expression were changed in 44%. Additional research is needed to gain insight on significance of change in gene expressions in order to provide information on treatment & outcomes. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. ix16 | abstracts Background: Inhibitors of the PD-1 pathway are effective in treatment of NSCLC. Expression of PD-L1 on tumour tissue can help predict response to therapeutic antibodies. To date, most trials involving targeted antibodies to PD-L1 in NSCLC have variable definitions of PD-L1 “positivity” on immunohistochemistry (IHC) with cutoffs ranging from 1% to 50% of cases. If patients are selected for, or are denied access to, a potentially effective treatment, it is important to have a biomarker that is reproducible between assessors. We evaluated the inter- observer agreement for PDL-1 IHC staining in a large cohort of resected NSCLC. Methods: A pathologist selected the site for triplicate cores of the primary tumour block from sequential patients with stage I-III NSCLC undergoing pneumonectomy or lobectomy at Austin Health. Tissue arrays were stained using the Dako 28-8 antibody inhouse by Bristol Myers Squibb (BMS). Arrays were scored by two independent, blinded assessors including one pathologist trained in scoring by BMS. The proportion of tumour cells with membranous staining of any intensity was scored. The Cohen’s kappa coefficient was calculated for each category to determine inter-observer agreement. Results: Tumour cores were from 517 patients, with 1503 evaluable samples from 1912 cores collected (78.6%). Preliminary analysis demonstrated agreement of the two scorers for 99.9%, 99.8% and 98.7% for tumours staining 1%, 5% and 50% of tumour cells respectively. Tumours staining for >1%, >5% and >50% had a kappa coefficient of 0.996 (95% CI 0.991 - 1.000), 0.994 (95% CI 0.987 - 1.000) and 0.920 (95% CI 0.885 – 0.956) respectively. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology Conclusions: Inter-observer agreement for PD-L1 IHC staining using the Dako 28-8 antibody is strong across all categories. The findings of this study suggest reporting of PD-L1 staining is reproducible between assessors. Legal entity responsible for the study: Austin Hospital Ethics Committee Funding: Austin Hospital Disclosure: G. Rivalland: Honoraria (for speaking engagements) AstraZeneca Roche. P. Mitchell: Honoraria- Roche, MSD Advisory board- BMS, Roche, AstraZeneca, MSD, Boehriner Ingelheim Other- Roche, BMS, AstraZeneca- travel and accommodation. All other authors have declared no conflicts of interest. 58P PDL1 expression associated with worse survival outcome in malignant pleural mesothelioma B. Nguyen1, R. Montgomery2, M. Fadia2, J. Wang3, S. Ali1 Department of Medical Oncology, The Canberra Hospital, Canberra, ACT, Australia, 2Department of Anatomical Pathology, The Canberra Hospital, Canberra, ACT, Australia, 3Statistical Consulting Unit, The Australian National University, Canberra, ACT, Australia 1 Background: There is currently a need to identify an effective prognostic biomarker to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed cell death receptor ligand (PDL1) has been studied as a prognostic and predictive biomarker in a number of tumours given its central role in anti tumoural immune response evasion. Immunotherapy targeting PD1 have also been shown to be promising in MPM. Three recent published analysis found PDL1 positivity to be an adverse prognostic factor for survival. This study aims to investigate the relationship between PDL1 expression in mesothelioma tissues and survival outcome. Methods: Fifty-three patients from a single institution diagnosed with MPM based on histopathology from 01/2006 to 12/2015 were reviewed. Formalin fixed, paraffin embedded tissue were stained with PDL1 (Clone Ventana SP263). PDL1 positivity was defined as > 1% membranous staining regardless of intensity, moderately positive was defined as 1-10% and highly positive was defined as 10%. R Statistical Analysis Package was used for analysis. Results: Fifty-three patients had available histopathology and data for analysis. Median age was 73, majority was male (46, 87%). Forty-one (77%) had ECOG between 0-2, and 12 had ECOG of 3 (22%). Thirty-six (68%) had epitheliod subtype, 7 (13%) sarcomatoid subtype, and 10 (19%) biphasic subtype. Thirty patients received best supportive care, 15 patients received chemotherapy and 8 patients received a combination of chemotherapy and radiotherapy. Fourteen (26.41%) patients were PDL1 negative, 17 (32.08%) moderate positive and 22 (41.51%) highly positive. PDL1 as a prognostic marker was independently associated with adverse outcome. Highly positive PDL1 expression correlated with worse prognosis (HR ¼ 2.38, 95%, CI ¼ 1.01,5.6, pvalue¼0.046). Median survival of PDL1 negative, and highly positive was 13 months and 5.5 months respectively. On multivariate analysis PDL1, ECOG>2 and histology subtypes were found to be independently associated with adverse outcome. Conclusions: Our analysis found a higher percentage of MPM patients with positive PDL1 (>1%) compared to other studies. Highly positive PDL1 expression was associated with significantly lower median survival time. Legal entity responsible for the study: The Canberra Hospital Funding: The Canberra Hospital Private Fund Practice Disclosure: B. Nguyen: Recipient of the Canberra Private Fund Practice. S. Ali: Medical Advisory board: Nivolumab and Pembrolizumab; Conference sponsorships, speaker fees Recipient of the Canberra Private Fund Practice. All other authors have declared no conflicts of interest. 59P Characterization of PD-L1 expression in Chinese non-small cell lung cancer patients with PTEN IHC as a means for sample quality screening X-C. Zhang1, C. Sun2, Z. Xie1, X. Cao2, J-J. Guo2, J-J. Yang1, X-N. Yang1, H. Dai3, J. Lee3, F. Xu3, Y-X. Zuo3, M. Chen3, J. He4, A. Kiermaier5, D. Shames6, G. Cheng2, Y-L. Wu1 1 Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou, China, 2Oncology Biomarker Development, Genentech, Inc., Shanghai, China, 3 Roche Product Development in Asia Pacific, Roche (China) Holding, Ltd., Shanghai, China, 4Oncology Product Development, Genentech, Inc., San Francisco, CA, USA, 5Oncology Biomarker Development, Genentech, Inc., Basel, Switzerland, 6Oncology Biomarker Development, Genentech, Inc., San Francisco, CA, USA Background: Cancer immunotherapy agents blocking the receptor and/or ligand of the programed death-1 (PD-1) pathway have demonstrated encouraging clinical utility in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate PD-L1 prevalence and its association with major clinical characteristics in Chinese patients with NSCLC. Volume 27 | Supplement 9 | December 2016 Methods: Formalin-fixed, paraffin-embedded (FFPE) surgical NSCLC samples from 300 Chinese patients (the exploratory cohort) were assembled into tissue microarray format. These samples were first stained for PTEN expression through immunohistochemistry (IHC) which serves as a surrogate for tissue quality. Only the ones with at least moderate staining intensity on internal positive control cells (e.g., stromal cells) were considered qualified for PD-L1 IHC with Clone SP142. PD-L1 expression was evaluated on both tumor cells (TCs) and immune cells (ICs). The results were correlated to baseline characteristics and clinical outcomes on standard-of-care treatment regimen. Results: PTEN IHC showed that 110 samples in the exploratory cohort qualified for PD-L1 IHC. With the TC1/IC1 ( 1% of all TCs or all ICs express PD-L1) cut-off, 41.7% of these samples were PD-L1þ. Clinical characteristics including gender, age, smoking status and disease stage do not correlate with PD-L1 expression. However, EGFR mutant patients seem to have lower PD-L1 level than wild-type patients (18.8% vs. 44.0%, p ¼ 0.083). Moreover, PD-L1 level seems to be a favorable prognostic factor for both overall survival (OS) [HR ¼ 0.58, 95% CI (0.33, 1.03)] and recurrence-free survival (RFS) [HR ¼ 0.55, 95% CI (0.32, 0.93)]. The PTEN-IHC-disqualified samples showed much lower PD-L1 positive rate (12.5%). The correlation between PD-L1 level and EGFR mutation status, OS or RFS was also significantly diminished. Conclusions: In this study, PD-L1 expression was detected in 40% of PTEN-IHCqualified Chinese NSCLC patient samples and negatively correlated with EGFR mutation. PD-L1 level was found to be a favorable prognostic factor for both OS and RFS. These findings are being verified in a separate cohort of 150 Chinese NSCLC samples (the validation cohort). Legal entity responsible for the study: Guangdong General Hospital Funding: Roche (China) Holding, Ltd. Disclosure: All authors have declared no conflicts of interest. 60P Expression of PD-L1 is associated with poor prognosis in breast cancer: A meta-analysis M. Zhang Medical Oncology, 3rd Affiliated Hospital of Harbin Medical University, Harbin, China Background: The association of programmed cell death 1 ligand (PD-L1) with the prognosis of various cancers has been a research topic of considerable interest. However, the prognostic value of PD-L1 remains controversial in breast cancer patients. Methods: A systematic search of the PubMed, EMBASE, and Cochrane Library databases was performed to identify the correlation between PD-L1 expression and clinicopathological features and overall survival (OS). Results: A total of 5 studies containing 2,546 cases were included. The combined hazard risk (HR) and its 95% confidence interval (CI) for OS was 1.76 (95% CI 1.09–2.82; P ¼ 0.02) for patients with tumors exhibiting PD-L1 overexpression. Subgroup analysis revealed that higher PD-L1 expression was associated with poor prognosis in Asian populations (HR 1.53, 95% CI 1.17–2.01; P ¼ 0.002) but not in non-Asian populations (HR 1.69, 95% CI 0.48–5.98; P ¼ 0.42). The pooled odds ratios (ORs) indicated that PD-L1 expression was associated with positive lymph nodal metastasis, higher histological grade, estrogen receptor (ER)-negative, and triple negative breast cancer (TNBC). Conclusions: Our findings indicate that PD-L1 expression is a promising biomarker for the prognosis of breast cancer, and these insights might be helpful in selecting the appropriate immunotherapy for breast cancer. Legal entity responsible for the study: N/A Funding: Natural Science Foundation of Heilongjiang Province [No.H201335] Disclosure: All authors have declared no conflicts of interest. 61P Tumor-infiltrating lymphocytes/macrophages and clinical outcome in breast cancer Y-S. Kim, J-S. Kim Surgery, Uijeongbu St. Mary’s Hospital, Uijeongbu City, Republic of Korea Background: Breast cancer is composed of the malignant tumor cells and tumor microenvironment, which includes inflammatory cells. The inflammatory cells, known as lymphocytes and macrophages, regulate and release inflammatory mediators with pro-angiogenic or pro-metastatic effects in breast cancer. Tumor infiltrating lymphocytes(TILs) and tumor-associated macrophages(TAMs) are regarded to play a key role in progression and metastasis of various tumors. We evaluated their correlation with clinicopathologic parameters and prognosis in breast cancer. Methods: A total of 73 patients with stage I to III breast cancer who underwent surgery at Uijeongbu St. Mary’s Hospital were included. The mRNA expression of CD163 and FoxP3 were investigated by quantitative reverse transcription polymerase chain reaction in fresh-frozen breast cancer tissues and adjacent non-cancerous breast tissues. Clinicopathologic parameters including tumor size, lymph node metastasis, stage, the doi:10.1093/annonc/mdw574 | ix17 abstracts expression status of hormonal (estrogen and/or progesterone) receptor, and human epidermal growth factor receptor-2 were analysed. Also, survival data were reviewed. Results: Tumor tissues had higher mRNA expression than normal tissues(p < 0.001). CD163 mRNA expression had no significant difference between two gourps. The median level of CD163 mRNA expression was significantly higher in T2-T4 tumors than in T1 tumors(p ¼ 0.001). No association was observed between FoxP3 mRNA expression and tumor size(p ¼ 0.109). Both CD163 and FoxP3 mRNA expression were associated with lymph node(LN) metastasis (p < 0.001, P ¼ 0.012, respectively). Survival data was categorized patients into two groups with low expression(<median) and high expression(>median). A high FoxP3 mRNA expression was significantly associated with a poor overall survival(p ¼ 0.016). In multivariate analysis, LNmetastasis and high FoxP3 mRNA expression were a significant prognostic factors for poor survival (HR:6.735; p ¼ 0.014/HR:4.312; p ¼ 0.029, respectively). ix18 | abstracts Annals of Oncology Conclusions: Our results showed that larger tumor size, advanced stage, lymph node metastasis were associated with high TAMs and TILs infiltration. In addition, high FoxP3 expression was one of the independent prognostic factors for overall survival in breast cancer. Legal entity responsible for the study: This study was approved by the Institutuinal review board of Uijeongbu St. Mary’s hospital(UC16SIS0079) Funding: N/A Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 Annals of Oncology 27 (Supplement 9): ix19–ix29, 2016 doi:10.1093/annonc/mdw575 62O_PR Non-adherence to adjuvant endocrine treatment and its determinants among early stage breast cancer patients W. Wulaningsih1, H. Garmo2, J. Ahlgren3, L. Holmberg2, M. van Hemelrijck2, M. Lambe4 1 MRC Unit for Lifelong Health and Ageing, UCL - University College London, London, UK, 2Division of Cancer Studies, King’s College London Guy’s Hospital, London, UK, 3Department of Oncology, Universitetssjukhuset Orebro, Orebro, Sweden, 4Department of Medical Epidemiology and Biostatistics, Karolinska Intitutet, Stockholm, Sweden Background: Non-adherence to adjuvant endocrine treatment (ET) among breast cancer patients has been associated with worse prognosis. We sought to identify factors affecting non-adherence to ET, taking into account determinants at baseline and followup. Methods: From linkage between Swedish national registers, we identified all women diagnosed with stage I-III, ER-positive breast cancer in Stockholm-Gotland, Uppsala€ Orebro and Northern Sweden between 2006 and 2009. A total of 4,413 women who had at least one dispensation of tamoxifen or aromatase inhibitors (AIs) and 5 years of follow-up were included in the analysis. A medical possession ratio (MPR) of < 80% was used to define non-adherents. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of non-adherence to ET. Results: During follow-up, 1,131 (25.6%) women became non-adherents. The following determinants of non-adherence were identified: age, marital status, region of diagnosis, private hospital, tumour size, lymph node metastasis, tumour grade, HER2 status, type of surgery, adjuvant chemotherapy, type of ET, pre-diagnostic hormone replacement therapy, the use of symptom-relieving drugs at baseline and during follow-up, baseline scores and any increase in Charlson co-morbidity index (CCI). In multivariable analysis, non-adherence was only associated with younger age (OR: 0.67; 95%CI: 0.500.90 and 0.66; 0.48-0.92 for age 50-65 and 65þ compared to < 50, respectively), marital status (OR: 1.40; 95%CI: 1.23-1.60 for single/divorced/widowed compared to married women), socioeconomic status (OR: 1.17; 95%CI: 1.00-1.37 and 1.60; 1.16-2.21 for white collar and being unemployed compared to blue collar workers, respectively), and pre-diagnostic use of hormone replacement therapy (OR: 1.57; 95%CI: 1.28-1.93). Conclusions: Our study identifies socioeconomic subgroups with increased risk of nonadherence that may be of use when measures for improving adherence are tested. Women with pre-diagnostic use of HRT may represent a biological subset with a disposition for side effects from ET. Legal entity responsible for the study: King’s College London Funding: King’s College London Disclosure: All authors have declared no conflicts of interest. 63O A nation-wide multicenter 10-Year (1999-2008) retrospective study of chemotherapy in Chinese breast cancer patients Q. Li1, P. Zhang1, Z. Yang2, J. Fan2, J. He3, B. Zhang4, H. Yang5, X. Xie6, Z. Tang7, H. Li8, Y. Qiao2 1 Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China, 2Cancer Epidemiology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China, 3 Department of Oncology Surgery, First Affiliated Hospital of Xi’an Jiaotong University (School of Medicine), Xi’an, China, 4Breast Surgery, Liaoning Cancer Hospital & Institute, Shenyang, China, 5Breast Surgery, Zhejiang Cancer Hospital, Hangzhou, China, 6Breast Surgery, Cancer Centre Sun-Yat-sen University, Guangzhou, China, 7Breast-thyroid Surgery, Central South University Xiangya No.2 Hospital, Changsha, China, 8Breast Surgery, Sichuan Provincial People’s Hospital. Sichuan Medical Science Academy, Chengdu, China Background: We aimed to evaluate trends and factors associated with chemotherapeutic decisions in Chinese females with breast cancer. Methods: We retrospectively analyzed demographic and pathological data along with chemotherapeutic information of 4211 breast cancer patients randomly selected from representative hospitals of 7 traditional areas in China between 1999 and 2008. Results: A total of 3271 cases (77.7%) received adjuvant chemotherapy (ACT), 558 (13.3%) received neoadjuvant chemotherapy (NACT), and 392 (9.3%) received chemotherapy for metastatic disease. In adjuvant settings, age, stage, HR and HER2 status were independent factors affecting the use of ACT (P < 0.001). Frequencies of ACT in stage I, II and III cases were 69.1%, 83.2% and 93.9%, respectively. Frequencies of ACT in age groups of 39, 40-49, 50-59, 60-69 and 70 years were 84.2%, 81.9%, 79.5%, 65.6% and 28.3%, respectively. The percentage of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) in ACT decreased significantly from 51.2% to 1.3% between 1999 and 2008, and the use of regimens containing both anthracyclines and taxanes increased from 14.4% to 45.4%, while anthracycline-based (without taxanes) regimens increased dramatically in the first 5 years (from 15.3% to 54.5%) and decreased gradually to 26.8% in 2008. More locally advanced compared to earlier stage patients received NACT (24.1% vs. 9.2%, p < 0.001), and percentage of regimens containing anthracyclines and taxanes increased from 2.4% to 43.8% during this period, while anthracycline-based (without taxanes) regimens increased in the first 6 years (from 24.4% to 70.4%) and decreased to 30.0% in 2008. In first-line chemotherapy, 87.5% of cases received combined chemotherapy. Among them, 34.9% received anthracyclines and taxanes, followed by taxanes plus platinum (21.7%) and vinorelbine plus platinum (16.5%). Conclusions: To our knowledge, this is the first nationwide multi-center study of chemotherapy in Chinese breast cancer patients. Major changes have taken place in chemotherapy for early and metastatic disease in China during this 10-year interval, which reflected the incorporation of key evidence and guidelines into Chinese medical practice. Legal entity responsible for the study: Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) Funding: Pfizer Disclosure: All authors have declared no conflicts of interest. 64O_PR High mammographic breast density predicts locoregional recurrence after modified radical mastectomy for invasive breast cancer: A case-control study Y-S. Huang1, J.L-Y. Chen2, S-H. Kuo3, Y-C. Chang1 Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan, 2 Oncology, National Taiwan University Hospital, Taipei, Taiwan, 3Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan 1 Background: We aimed to evaluate the influence of mammographic breast density at diagnosis on the risk of cancer recurrence and survival outcomes in patients with invasive breast cancer after modified radical mastectomy. Methods: This case-control study included 123 case-control pairs of women diagnosed with invasive breast cancer between 2004 and 2009 who had undergone modified radical mastectomy and had mammographic breast density measured before or at diagnosis. Women with known locoregional recurrence or distant metastasis were matched to women without recurrence by pathological disease stage, age, year of diagnosis, hormone receptor status, Her2 status, and adjuvant hormone or trastuzumab administration. Locoregional recurrence included recurrence in the ipsilateral breast, axillary or supraclavicular nodes, or contralateral breast. The median follow-up duration was 60.8 months for case patients and 61.3 months for control patients. Results: Patients with heterogeneously dense (50–75% density) and extremely dense breasts (>75% density) had an increased risk of locoregional recurrence (hazard ratios, 3.9 and 8.4; 95% confidence intervals, 1.1–14.1 and 1.4–67.6; and p ¼ 0.033 and 0.024, respectively). Multivariate analysis that included a lack of adjuvant radiotherapy and triple negative cancer revealed that dense breasts (>50% density) remained a significant factor for predicting locoregional recurrence risk (hazard ratio, 4.9; 95%; confidence interval, 1.4–17.3; and p ¼ 0.013). Conclusions: Our results demonstrate that dense breast tissue (>50% density) conferred a greater risk of locoregional recurrence after modified radical mastectomy in patients with invasive breast cancer. Additional prospective studies are necessary to validate these findings. Clinical trial indentification: NCT02771665 Legal entity responsible for the study: National Taiwan University Hospital Funding: Ministry of Science and Technology (MST, Taiwan, under contract of MST 105-2314-B-002-022-) Disclosure: All authors have declared no conflicts of interest. C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts Breast cancer, early stage abstracts 65PD Significance of preoperative fine-needle aspiration biopsy for suspected cases of lymph node metastasis in primary breast cancer A. Ogiya1, T. Iwase1, N. Teruya1, H. Sakamoto1, E. Nakashima1, A. Kataoka1, D. Kitagawa1, T. Sakai1, H. Morizono1, Y. Miyagi1, R. Horii2, F. Akiyama3, S. Ohno4 1 Breast Surgical Oncology, Cancer Institute Hospital of JFCR, Tokyo, Japan, 2 Department of Pathology, Cancer Institute Hospital of JFCR, Tokyo, Japan, 3 Department of Pathology, Cancer Institute of JFCR, Tokyo, Japan, 4Breast Oncology Center, Cancer Institute Hospital of JFCR, Tokyo, Japan Background: In patients diagnosed with breast cancer, preoperative assessment of the lymph nodes is performed by palpation and ultrasonography (US). In suspected cases of metastasis, the lymph nodes are evaluated by fine-needle aspiration (FNA) biopsy. In recent years, in some cases, dissections are omitted even if metastasis to the lymph nodes is detected. Thus, among cases where dissection can be omitted even when metastasis is observed, there have been some cases where dissection was initially performed when metastasis was verified by preoperative FNA. The aim of this study was to evaluate the significance of performing preoperative FNA for suspected cases of lymph node metastasis. Methods: The study involved 745 patients with cStage I/II primary breast cancer who had undergone axillary dissection. Patients were divided into four groups based on the presence or absence of palpable lymph nodes, US findings, and FNA results: (1) the cN0 group: non-palpable lymph nodes, normal US findings, and no FNA evaluation; (2) the cN?FNA (-) group: non-palpable lymph nodes, US revealed suspicion of metastasis, and FNA revealed no metastasis; (3) the cN?FNA (þ) group: non-palpable lymph nodes, US revealed suspicion of metastasis, and FNA revealed metastasis; and (4) the Stage II group: non-palpable or palpable lymph nodes, US revealed metastasis, and FNA revealed metastasis. Using the above four categories, we compared the number of lymph node metastasis in each group. Results: The median number of lymph node metastasis in the cN0, cN?FNA (-), cN?FNA (þ), and Stage II groups was 2, 2, 3, and 3, respectively. The percentage of 1-2 lymph nodes metastasis was 74%, 64%, 44%, and 46%, respectively. The percentage of 10 lymph nodes metastasis was 2%, 3%, 15%, and 11%, respectively. Distribution of the number of lymph node metastasis between the cN0 and cN?FNA (-) groups, and between the cN?FNA (-) and cN?FNA (þ) groups differed significantly. In contrast, the distribution of the number of lymph node metastasis in the cN?FNA (þ) and Stage II groups showed no significant differences. Conclusions: Our study reveals that cN1 patients can be accurately identified from among those suspected of having lymph node metastasis based on FNA findings. Legal entity responsible for the study: Cancer Institute Hospital, Tokyo, Japan Funding: N/A Disclosure: All authors have declared no conflicts of interest. 66PD Comparison of blue dye and radio-tracer markers for identification of axillary sentinel node in patients with early breast cancer P. Loza1, J. Eglitis2, K. Arcimovica2 1 Breast Surgery, Latvian Oncology Center Rakus Gailezers, Riga, Latvia, 2 Breast Health Department, Latvian Oncology Center Rakus Gailezers, Riga, Latvia Background: Sentinel lymph node biopsy is a standard procedure in treatment of early breast cancer. However, the technique itself and the use of lymphatic markers remain generally unstandardized. Aim of this study is to compare efficacy of sentinel node biopsy using methylene-blue dye, radioactive colloid and dual marker technique. Methods: Prospective study includes patients with early breast cancer treated in a single institution from year 2013 to 2015. Three subgroups were created according to the method of lymphatic marking (A¼blue dye, B¼radioactive technetium, C¼dual markers). Sentinel identification rate and the number of marked sentinel nodes was compared between groups. Concordance between two lymphatic markers was assessed using Cochrane’s Kappa statistical method. Results: Study includes total of 204 patients. Sentinel node identification rate (95% CI) was 87.4% (þ/- 6.5%) in group A, 94.1% (þ/-8.7%) in B and 100% (þ/- 2.6%) in group C. Median number of marked nodes was one node. There were more hot nodes in group C than in groups A and B (P ¼ 0.002). In group C, concordance index between blue dye and radioactive tracer was relatively weak (kappa¼0.049, 95% CI 0-0.244). Conclusions: Radioactive tracer can be used as single lymphatic marker, however, for best results dual marking is recommended. Methylene blue dye and radioactive Technecium colloid can be considered as complimentary when used simultenously. The use of blue dye as a single lymphatic marker is not recommended because of unacceptably low sentinel identification rate. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. ix20 | abstracts Annals of Oncology 67PD Quality of life after risk-reducing salpingo-oophorectomy in BRCA carrier Y. Jang, E. Kang, E. Kim, S. Chae, H. Kim General Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea Background: Risk-reducing salpingo-oophorectomy (RRSO) is generally recommended for women with BRCA1 or BRCA2 mutation at age 35 and more. However, the menopause symptoms induced by RRSO may decrease quality of life (QOL). In Korea, the influence of RRSO to carrier’s QOL has not been evaluated. This study was designed to compare the QOL and menopausal symptoms between RRSO and non-RRSO group. We also evaluated the change of QOL before and after RRSO among subgroup who had RRSO. Methods: Total of 45 women with BRCA1 or BRCA2 mutation at age 35 and more were included in this study. Outcomes were measured using the forms including SF-36v2 for QOL, STAI-1 for anxiety, Beck Depression inventory for depression, LOT-R for optimism, CAREs for sexual function and MRS for menopausal symptoms. This study was approved by the institutional review board of Seoul National University Bundang Hospital. Results: In total, 26 women underwent RRSO and 19 women did not. The mean age in RRSO group (49.0 years) was statistically higher than that in non-RRSO group (42.7 years). However, other demographic factors (age, education, income, occupation, marital status, family history, and underlying disease) were not different between two groups. The scores for mental QOL, depression, optimism, sexual function and menopause were similar between RRSO and non-RRSO groups. Only physical QOL in non-RRSO group (62.2) was higher than that in RRSO group (56.3), with a trend toward significance (p ¼ 0.07). Among 26 women with RRSO, 11 were evaluated for QOL and psychological status before RRSO. As a result of analyzing, the change of QOL and emotional status before and after RRSO among the 11 women, only physical QOL after RRSO (57.4) was significantly higher than before RRSO (45.1) (p ¼ 0.004). Conclusions: Our study did not show a significant difference in QOL and menopausal symptoms according to RRSO. Only physical QOL was significantly improved after surgery among subgroup with RRSO. Legal entity responsible for the study: Departement of General Surgery, Seoul National University Bundang Hospital Funding: N/A Disclosure: All authors have declared no conflicts of interest. 68PD BRCA1/2 mutation analysis in Indonesian hereditary breast cancer revealed frequent variants of uncertain significance S. Haryono1, S. Utami2 1 Surgical Oncology, Dharmais Hospital, National Cancer Center, Jakarta, Indonesia, 2Oncology Research, Siloam Hospital Semanggi MRCCC, Jakarta, Indonesia Background: The contribution of genetic mutation associated with higher risks for Hereditary Breast and Ovarian Cancer Syndrome breast-ovarian cancers in the Indonesian population has been relatively unknown. Methods: There were 41 unrelated cases from two cancer centers in Jakarta, Indonesia. The patients were characterised by their family history, which demonstrated that they had either moderate or high risks for breast cancer. BRCA1/2 mutation analyses were accomplished with direct sequencing. Results: Deleterious mutations were found in one patient with large deletion in exon 15 of BRCA1. Forty-seven variants at BRCA2 genes were documented in 21 of 41 patients (51%). All variants were categorized as unclassified variants (VUSs). Two synonymous variants, c.3623A>G and c.4035T>C, were found in 5 patients. A variant, c.3396A>G was reported in 9 patients. One variant, c4600T>C, was found in a 38-year-old woman with family history of breast cancer. Four novel variants in BRCA2 gene were found: c.6718C>G, c.3281A>G, c.10176C>G, and c4490T>C, in 4 unrelated patients, all of whom had positive family history of breast cancer. Six different variants of BRCA1 were reported in 7 unrelated patients. Conclusions: In accordance to other studies in Asian population, our study showed more frequent variants in BRCA2 than BRCA1. Further studies involving larger hereditary breast cancer patients are still developing to reveal the contribution of BRCA1/2 mutations and/or other susceptibility genes among hereditary breast cancer patients in Indonesia. Legal entity responsible for the study: Dharmais Hospital, National Cancer Center and Mochtar Riady Comprehensive Cancer Center, Siloam Hospital Semanggi. Funding: Dharmais Hospital, National Cancer Center and Mochtar Riady Comprehensive Cancer Center, Siloam Hospital Semanggi. Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology 69P Cisplatin based preoperative chemotherapy regimens for basal-like breast cancer potentially improve prognosis even in patients without pCR: A retrospective analysis from a single-institution A. Yamaguchi1, H. Ishiguro2, M. Torii1, M. Takada1, E. Suzuki1, M. Takeuchi1, F. Sato1, M. Toi1 1 Breast Surgery, Kyoto University-Graduate School of Medicine, Kyoto, Japan, 2 Department of Target Therapy Oncology, Kyoto University-Graduate School of Medicine, Kyoto, Japan Background: The extent of residual disease after preoperative chemotherapy is a strong prognostic factor in triple-negative breast cancer. Cisplatin has been incorporated into many chemotherapy regimens for various tumor types in the curative setting; however, its role in breast cancer has not been well established. Methods: Fifty-eight previously untreated, stage I–III basal-like breast cancer patients treated with or without cisplatin based preoperative chemotherapy regimens from 2007 to 2015 in the Kyoto University Hospital, were consecutively included in the present analysis. Patient characteristics such as tumor size, nodal status, age, tumor grade, Ki-67 status, and estrogen receptor status were retrospectively acquired. All patients were divided into four groups based on their pCR status (with and without) and the inclusion of cisplatin (with and without) in the treatment regimen. Event-free survival (EFS) was analyzed using the Kaplan–Meier method. Results: Thirty-six cases were treated with cisplatin-based regimens and 22 were treated without cisplatin. The median follow-up period was 4 years and pCR was achieved in 27.3% and 52.8% of the patients treated with and without cisplatin-based regimens, respectively. All patients who achieved pCR were recurrence-free. In the groups without pCR, the 4-year EFS rates with and without cisplatin were 92.9% and 65.6%, respectively. Multivariate analysis indicated that pCR and the use of cisplatin were significant factors of EFS (Table). Table: 69P Multivariate analysis (Event-free survival) Prognostic factors Hazard ratio P value Age (>54 years, <54 years) Tumor size (>50 mm, <50 mm) Nodal status (cN0, cNþ) Cisplatin regimen pCR 3.394 0.210 0.207 0.091 >0.001 0.2333 0.0900 0.1313 0.0460 0.0417 Conclusions: Despite the relatively small patient cohort, our data indicated that cisplatin based chemotherapy improved EFS even in patients without pCR. Cisplatin based preoperative chemotherapy might confer long-lasting anti-tumor activity, leading to better prognosis even in patients without pCR. Legal entity responsible for the study: Kyoto University Medical Ethics Committee Funding: Grants-in-Aid for Scientific Research Disclosure: All authors have declared no conflicts of interest. Conclusions: Patients with HER2þ and RDI more than 85% appeared to have favorable histological therapeutic effect. This study also showed that “early tumor shrinkage” might be a novel predictive factor relating to pCR. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 71P C. Bandidwattanawong1, N. Chalermsuksant2 Medical Oncology Unit, Department of Internal Medicine, Bangkok Metropolitan Administration Medical School and Vajira Hospital, Bangkok, Thailand, 2Department of Internal Medicine, Bangkok Metropolitan Administration Medical School and Vajira Hospital, Bangkok, Thailand 1 Background: Breast cancer is the most common cancer among female Thais. Molecular intrinsic subtyping is the best method to classify patients into groups of different prognosis and probably guidance of proper treatment. Intrinsic subtyping based on St Gallen 2013 Expert Concensus using IHC for ER, PR, HEr-2 and Ki-67 is more practical way, however validation in Thai early breast cancer patients was never done. Methods: We collected data of early breast cancer patients treated in Vajira Hospital from January 1, 2006 to December 31, 2011. There were 171 patients eligible. Baseline characteristics including age, staging, treatments, patterns of recurrence were recorded. No central review for IHC for ER, PR and HER-2 were done. Ki-67 was determined by our institute’s pathologists. Primary aim was to calculate the prevalence of breast cancer patients of different subtypes stratified by St Gallen 2013 Concensus. Secondary ones were to determine patterns of recurrences and survival among patients with different subtypes. Results: We stratified our patients based on only IHC results according to St Gallen 2013 Expert Consensus criteria. There were 32.7% LuA, 30.4% LuB, 18.7% HER-2enriched and 18.1% triple negative. OS (95%CI) of patients with LuA was 103.17(93.54112.80), LuB 105.63 (95.46-115.80), HER-2-enriched 87.5 (66.76-108.24) and triple negative 95 (72.72-103.48) months. More patients with LuB subtype had bone and soft tissue metastases. Visceral metastases were found more in patients with HER-2enriched and triple negative subtypes. Lu A subtype was the only prognostic factor survival regardless of nodal status. Prevalences and survival patterns imitated the data from studies using multi-gene assay. Conclusions: Stratification of ealy breast cancer patients into subtypes based on 2013 St Gallen Expert Consensus is robust in routine practice. It is the cheaper and more practical tool compared to costly molecular techniques. Clinical trial indentification: COA 26/2559 Legal entity responsible for the study: Research Facilitation Division, Faculty of Medicine Vajira Hospital Funding: Research Facilitation Division, Faculty of Medicine Vajira Hospital Disclosure: All authors have declared no conflicts of interest. 72P 70P “Early tumor shrinkage” might be a novel predictive factor relating to pCR in neoadjuvant chemotherapy for resectable breast cancer T. Saiki1, A. Ishiguro1, M. Abe2, Y. Tabata2, H. Kato2, Y. Narita2 1 Medical Oncology, Teine Keijinkai Hospital, Sapporo, Japan, 2Breast Surgery, Teine Keijinkai Hospital, Sapporo, Japan Background: Administering 100mg/m2 of epirubicin and cyclophosphamide(EC) followed by taxanes and/or trastuzumab is the standard treatment for resectable breast cancer as neoadjuvant chemotherapy at our institution. The objective of this study is to clarify efficacy and safety of the treatment. Methods: Between March 2010 and April 2016, fifty-four female patients with locally invasive ductal carcinoma who received neoadjuvant chemotherapy were reviewed retrospectively. This study investigated the correlation between pathological complete response (pCR) and clinicopathological factors in clinical and histological therapeutic response. We defined the pCR as ypT0 ypN0 or ypT0/is ypN0. Results: Patient characteristics were as follows. The median age was 55.3 years (31-79). Patients(pts) were classified into 6 groups in this study (luminal A: 4, luminal B (HER2): 16, luminal B (HER2þ): 10, HER2þ: 10, triple negative: 10, undeterminable hormone-positive: 4). Histological therapeutic effect of more than Grade 2 was 29 pts (53.7%). The pCR rate was 20.4% (luminal B (HER2-): 2, luminal B (HER2þ): 1, HER2þ: 4, triple negative: 4). Relative dose intensity (RDI) more than 85% in treatment with neoadjuvant EC was 87.0% and all patients of the pCR were included. Patients who achieved partial response in RECIST just after first 2 cycles of EC had significantly higher pCR rate (p ¼ 0.030). Volume 27 | Supplement 9 | December 2016 Is St Gallen 2013 intrinsic subtype classification valid in routine practice? The different prognostic impact of age according to individual molecular subtypes in breast cancer Y.H. Eom, B.J. Song, B.J. Chae, S.H. Yoo Surgery, Seoul St. Mary’s Hospital, of the Catholic University, Seoul, Republic of Korea Background: Young age at diagnosis has been considered as a poor prognostic factor in breast cancer. But, it is unjust to consider that young age is the independent poor prognostic factor for all breast cancer. We analyzed the different prognostic impact of age according to molecular subtypes. Methods: Our study retrieved data from 1,410 patients with primary breast cancer who underwent surgery and the adjuvant treatment between 2007 and 2011. The association of age and molecular subtypes with recurrence free survival(RFS) and disease specific survival(DSS) was assessed using Kaplan-Meier analysis, univariate and multivariate analysis. Results: Patients aged <40 years had higher proportion of triple negative breast cancer(p < 0.001), and had significantly shorter RFS than patients aged 40-50 years and >50 years(p ¼ 0.047). There was no statistically difference in DSS(p ¼ 0.412). In subgroup analysis according to molecular subtypes, inferior RFS was observed for patients aged <40 years with only luminal A breast cancer(p ¼ 0.017). Multivariate analysis revealed that age and tumor size were independent prognostic factors for RFS (HR, 3.04; 95% CI, 1.39-6.64; p ¼ 0.005) in luminal A breast cancer. No difference according to molecular subtypes was observed in DSS. doi:10.1093/annonc/mdw575 | ix21 abstracts Conclusions: Age at diagnosis of breast cancer had different role for prognosis according to molecular subtypes. Age itself is not the independent prognostic factor. Age <40 years had limited worse prognostic impact only in luminal A breast cancer being exposed to high level of estrogen during longer period even after completion of 5year endocrine therapy. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 73P Annals of Oncology confidence interval [CI] 1.417-2.924), as well as OS (P < 0.01, HR 2.501, 95% CI 1.497– 4.176). Conclusions: Although the precise molecular mechanism of serum miR-21 increase following radiotherapy would require further clarification, the finding indicated that miR-21 might be a good candidate as a molecular prognostic marker, and predictive marker of radiotherapy in breast cancer. Legal entity responsible for the study: N/A Funding: Babol university of medical sciences Disclosure: All authors have declared no conflicts of interest. Change in the bone absorption marker levels in aromatase inhibitor-treated patients who were switched from oral bisphosphonates to denosumab Y. Mizuno Breast Surgery, Yokkaichi Municipal Hospital, Yokkaichi City Mie, Japan 75P Outcomes in postmenopausal women with hormone receptor positive, HER-2 negative T2N0 breast cancer without adjuvant chemotherapy Y.S. Kim1, B.S. Ko2 Surgery, Chosun University College of Medicine, Gwnagju, Republic of Korea, 2 Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea 1 Background: Aromatase inhibitors (AIs) are known to increase the risk of fractures and reduce bone mineral density in postmenopausal patients with estrogen receptor (ER)positive breast cancer. The ABCSG-18 trial demonstrated that denosumab significantly increased bone mineral density in patients with non-metastatic breast cancer who were receiving AIs. However, the effect of denosumab in patients who have received treatment with oral bisphosphonates for the prevention of bone loss and factures is still unknown. Methods: Between January 2015 and January 2016, we enrolled 21 postmenopausal patients with ER-positive breast cancer. Of these patients, 10 were switched from oral bisphosphonates to denosumab (switch group) and 11 were treated with denosumab for the first time (initial group). The mean age was 74 years (range, 61–84 years) in the convert group and 71 years (range, 58–83 years) in the initial group. The mean T-scores for the lumbar spine and femoral neck, assessed by using dual-energy radiographic absorptiometry, were respectively 2.9 (range, 1.8 to 3.9) and 2.5 (range, 2.0 to 4.2) in the switch group, and 2.0 (range, 0.6 to 3.5) and 2.3 (range, 1.3 to 2.8) in the initial group. All the patients concurrently received vitamin D2 (ergocalciferol) supplementation with AIs. The percent change in urine N-telopeptide crosslinked type 1 collagen (u-NTx) level was measured at baseline and after 1 month of denosumab therapy. Results: In the switch group, 8 of 10 patients had a decreased change in u-NTX level, which was above the maximum significant change (27.3%). The mean percentage change in u-NTX level was 54.1% (95% confidence interval [CI], 40.3–67.9%). On the other hand, 10 of 11 patients in the initial group had a decreased change, with a mean percentage change in u-NTX level of 60.0% (95% CI, 42.7–77.2%). None of the patients had adverse reactions, including hypocalcemia, backache, and arthralgia. Conclusions: After switching oral bisphosphonates to denosumab, the mean percent change in u-NTX level was similar to that in the initial use of denosumab. We suggest that clinicians should switch oral bisphosphonates to denosumab for the prevention of AI-induced bone loss and fractures. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 74P Clinical translation of serum microRNA 21 as a potential prognostic marker in breast cancer patients and predictive marker of radiotherapy D. Moslemi1, H. Parsian2, M. Halimi2 Radiation Oncology, Babol University of Medical Sciences (BUMS), Babol, Iran, 2 Biochemistry, Babol University of Medical Sciences (BUMS), Babol, Iran 1 Background: With regard to the variability in clinical progression of breast cancer, the identification of markers capable of predicting tumor behavior and its therapeutic response would be of paramount importance. The present study assessed the potential of circulating miR-21 in functioning as a prognostic marker and predictive marker of radiotherapy in breast cancer patients. Methods: Patients We investigated serum level of miR-21 in a cohort of 40 breast cancer patients before and after radiotherapy in addition to 20 healthy age- and gendermatched volunteers. Moreover, the prognostic and predictive value of miR-21 was determined through exploring the correlation between expression levels of miR-21 before and after radiotherapy and local recurrence, progression-free survival (PFS) and overall survival (OS). Results: The results showed a significant increase in serum miR-21 level after radiotherapy (P < 0.001). The univariate Cox regression analyses of miR-21 serum level after radiotherapy revealed a significant association between miR-21 serum concentration after radiotherapy and PFS (P < 0.01, hazard ratio [HR] 2.036, 95% ix22 | abstracts Background: Cytotoxic chemotherapy for breast cancer after surgery is one of the most important systemic therapy to reduce the recurrence rates and mortality rates. However, chemotherapy in elderly women with low risk, hormone receptor positive breast cancer still inspires controversy. We report the outcomes in postmenopausal women with hormone receptor positive, HER-2 negative T2N0 breast cancer without adjuvant chemotherapy. Methods: We analyzed retrospectively 207 postmenopausal women with hormone receptor positive, HER-2 negative T2N0 invasive breast cancer who underwent surgery at Asan Medical Center (Seoul, South Korea) from January 2000 to December 2008. The patients were devided two groups: endocrine therapy only (ET, n ¼ 71) and adjuvant chemotherapy followed by endocrine therapy (CET, n ¼ 136). Results: ET group was older (p ¼ 0.000) and less received adjuvant radiotherapy (p ¼ 0.003) than CET group. There was more lymphovascular invasion in CET group than ET group (p ¼ 0.001). ET group showed a higher degree of progesterone receptor expression (p ¼ 0.048). In multivariate analysis, lymphovascular invasion was the only factor affecting risk of death and recurrence. There was no statistical significance in disease free survival rate, overall survival rate and disease-specific survival rate between two groups. Conclusions: Some postmenopausal women with hormone receptor positive, HER-2 negative T2N0 breast cancer may avoid chemotherapy on the basis of biologic characteristics, comorbidity, social support, functional status, and patient’s preferences. Tailored adjuvant therapy for early-stage breast cancer patients is an important goal. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 76P Invasive lobular breast cancer, a 14 years experience at single cancer hospital from Pakistan. S. Ali Medical Oncology, Shaukat Khanum Memorial Cancer Hospital and Reserch Centre (SKM), Lahore, Pakistan Background: Invasive lobular breast cancer, relatively uncommon variety of breast cancer is considered more responsive to hormonal therapy as compared to chemotherapy. We looked at the outcome of our patients with lobular invasive breast cancer retrospectively in last 14 years Methods: Data of all patients of non-metastatic ILC treated from 2000 to 2013 was collected. Baseline characteristics including hormone receptor status, type of surgical procedure performed, type and intent of chemotherapy and type of hormonal therapy given was documented. Number of margin positive resections requiring reexcision were noted and compared according to type of surgery. Kaplan Meier method and log rank test was used to calculate survival based or hormone receptor status. Multivariate analysis was performed using Cox regression analysis to see the impact of various baseline clinical characteristics on survival. Results: Two hundred and nineteen patients were including, all of them female, mean age was 51.5 years. Breast conservative surgery was performed in 28.4% patient with positive resection margins in significant number compared to mastectomy requiring reexcision: 31.1% versus 2.5% (p < 0.001). Seventy eight percent patients received anthracycline, 8.2% patients received non-anthracycline based chemotherapy, while 13.7% patients received only hormonal therapy. Ninety six percent patients with hormone receptor positive disease received adjuvant hormonal therapy. Patients with hormone receptor positive disease had significantly better median progression free and overall survival compared to hormone receptor negative disease, 114.2 versus 25.4 months (p ¼ 0.001) and 115.2 versus 56.4 months (p ¼ 0.006) respectively. Tumor size, Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology node positivity and hormone receptor status proved independent prognostic factors on multivariate analysis. Conclusions: Tumor size, nodal status and especially hormone receptor status quite significantly affect the outcome in Lobular invasive breast cancer. Mastectomy gives better result than breast conservative surgical procedure Legal entity responsible for the study: Shaukat Khanum Memorial Cancer Hospital and research Centre, Lahore, Pakistan was responsible for the governance, coordination and running of the study. Funding: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore Disclosure: All authors have declared no conflicts of interest. 77P Table: 78P BIRADS 0 1 2 3 4 5 Fault-Technical TOTAL Menarche age, contraception use and gravidity as risk factors for breast cancer: Associations in a case-control study D. Moslemi, M. Ghanbari, S. Esmaelzade, M. Agajani Delavar Gynecology, Babol University of Medical Sciences (BUMS), Babol, Iran Background: high incidence of Breast cancer (BC) in recent years has been considered as a major problem of female’s health. We aimed to share our experience for focusing on some of risk factors for (BC) among patients who referred to Shahid Rajai radiotherapy center Babolsar, Mazandaran, Iran Methods: A Case-Control study of (BC) obtained from patients who referred to Shahid Rajai radiotherapy center in babolsar. A total of 810 cases with histologically confirmed BC between September 2012 and February 2015 were enrolled. Controls, N ¼ 840, were matched frequency to cases by 5-year age group. Data from both groups by questionnaire was collected. To assess associations between each risk factor and BC risk logistic regression applied with 95% confidence intervals and adjusted odds ratios Results: The mean age of case and control group was 46.5768.33 and 46.9969.94 years, moreover the mean age of menarche in case and control group was 11.8361.34 and 12.0060.44 years, respectively. In multivariable models, Menarche age (OR ¼ 4.04, 95% CI: 2.48 -6.59), gravidity (OR ¼ 0.18, 95% CI: 0.13-0.24), and contraception use history (OR ¼ 6.04, 95% CI: 4.71-7.76) were the strongest predictors of BC in our study population Conclusions: Nulligravidity and high duration of using contraception are Modifiable factors that women can modify them and lower age of menarche also had a strong association with (BC). Legal entity responsible for the study: Babol University of Medical Sciences Funding: Babol University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. 78P Results: Population based mammographic screening in India: Analysis from community outreach cancer screening program S.S. Bisht1, T. Kataria1, D. Gupta1, A. Abhishek1, S. Goyal1, T. Basu1, K. Narang1, M. Tayal1, S. Banarjee1, J. Arora2, S. Razdan3 1 Radiation Oncology, Medanta Cancer Institute, Medanta The Medicity, Gurgaon, India, 2Radiology, Medanta Cancer Institute, Medanta The Medicity, Gurgaon, India, 3Breast Surgery, Medanta Cancer Institute, Medanta The Medicity, Gurgaon, India Background: Breast cancer is increasing in the developing countries. The risk factors are not easily modifiable therefore secondary prevention with screening is the way forward. Mammography (MG) remains the main modality of screening with significant decrease in breast cancer mortality. Most of this evidence is from developed countries. Demographics and tumor biology of Indian breast cancer patient is different from western world. Thus similar benefit of screening MG in India is debated. Furthermore data on MG in Indian population is not available. Methods: Breast cancer screening through mobile MG van (Siemens) was inducted in 2012 as a part of community outreach program (Health camps) at our hospital. Asymptomatic females above the age of 40 years, who attended the health camps underwent bilateral breast (craniocaudal and mediolateral view) screening MG after consultation with oncologist. Females younger than 40 years with family history of breast cancer also underwent the test after the risk/benefit discussion. All MG were reported by in-house radiologist and cases were informed for any further action. MG data of 4106 cases from 169 camps conducted in urban and suburban region of north and central India between Feburary 2012-May 2016 were selected. Cases with history of breast cancer and unilateral MG were excluded (n ¼ 104). 4002 patients were selected. Patient were segregated in age bins: <40 yrs; 40-49yrs; 50-59 yrs; 60-69yrs and more than 69 years. BIRADS score, tissue density, MG findings and laterality were noted. Cases with score 3 and above are being traced for the ultimate presence or absence of breast cancer after the MG intervention (Personal communication is in progress). Volume 27 | Supplement 9 | December 2016 N % 802 2239 437 421 56 15 32 4002 20 55.9 10.9 10.5 1.39 0.37 0.8 100 Mean Age SD 70 þ (%) <40YRS 40-49 50-59 60-69 (%) (%) (%) (%) 47 51.9 55.1 50.3 49.9 52.8 7.3 8.8 9.8 8.5 9.7 8.18 8.45 3.4 1.6 5.22 5.35 6.67 60.45 40 29.2 45.13 46.4 26.67 23.23 35.4 34.05 34.44 33.92 40 6.52 16.95 26.15 12.58 7.14 26.67 1.33 4.25 9 2.61 7.14 0 51.2 9 4.35 42.86 33.16 15.53 4 Conclusions: The average age of screened population was 51 years with majority of population (76%) in the 40-59 years. 20% of population was above 60 years. The incidence of BIRADS 0-2 was 87% . BIRADS 3 was 10.5% in overall population. BIRADS 4-5 constitutes 1.76%. Legal entity responsible for the study: Medanta The Medicity Funding: N/A Disclosure: All authors have declared no conflicts of interest. 79P Molecular targeted therapy for Her2 positive breast cancer in private sector: Yangon experience M. Khine1, S. Mon2, N. Sein1, T.T. Aye2, S.S. Htay2, N.H. Kyaw1, E.P.P. Aung1, P.T. Hnin1 1 Oncology, Thurein Oncology Clinic, Yangon, Myanmar, 2Medical Oncology, Bahosi Medical Centre Bahosi Housing Complex, Yangon, Myanmar Background: Trastuzumab in combination with chemotherapy is approved for treatment of early and metastatic Her2 over expressing breast cancer and shown to increase survival. But cost of trastuzumab makes the patients hurdle to get access the standard treatment in low income countries. Methods: Clinical data of patients with breast cancer at 3 private clinics in Yangon, Myanmar from July 2014 to June 2016 were studied and analyzed for molecular subtype distribution and access to Her2 targeted therapy in Her2 positive breast cancer patients. Results: Including 2 male breast cancer patients, a total of 488 breast cancer patients were registered. Mean age is 52.73 yrs (range 22yrs - 87yrs). Invasive duct carcinoma were 92% (n ¼ 449). Biological markers ER, PR, Her2 status were done with Immunohistochemistry method in 82.5% (n ¼ 407) whereas 8.23% were not done the test due to financial limitations. Molecular subtypes were 39.8% (n ¼ 162) with ER positive Her2 negative and 17.93% (n ¼ 73) with Triple Negative Breast cancer. Total Her2 positive patients were 37.83% (n ¼ 154) which was relatively high number and all were female. 4.5% of Her2 positive patients were Stage I, 70.12% were Stage II and 18.18% and 7.14% were Stage III and IV. 42 patients (27.27%) received Trastuzumab therapy either intravenous or subcutaneous injection forms. 3 patients with advanced cancer also received combination with Pertuzumab. Among 42 patients, 3 patients stopped trastuzumab treatment after 8th and 9th cycle due to financial catastrophe during therapy. Conclusions: Although there is patient assistance program to get access for Trastuzumab for Her2 positive breast cancer in Myanmar, still limited number of patients can afford for the treatment in private sector cancer care. Access to treatment and cost of therapy are barriers for Her2 targeted therapy in developing countries like Myanmar where the health care expenditure is totally out of pocket for cancer patients. Legal entity responsible for the study: Thurein Oncology Clinic Funding: Thurein Oncology Clinic Disclosure: All authors have declared no conflicts of interest. 80P A retrospective review of breast cancer care in North Okkalapa Hospital, Yangon, Myanmar N. Sein1, S. Mon2, M.M. Lwin1 Oncology, North Okkalapa General Hospital, Yangon, Myanmar, 2Oncology, Bahosi Medical Centre Bahosi Housing Complex, Yangon, Myanmar 1 Background: North Okkalapa Hospital is a 800 bedded hospital located in North Okkalapa township, eastern part of Yangon and affiliated teaching hospital of the University of Medicine 2, Yangon. The medical oncology team consists of two medical doi:10.1093/annonc/mdw575 | ix23 abstracts Annals of Oncology oncologists and four medical and nursing staffs; has been serving for cancer care in solid tumours since January 2013. This study aims to explore breast cancer management in a tertiary care hospital in Yangon, Myanmar. Methods: Clinical data of breast cancer patients registered from Jan 2013 to June 2016 were reviewed and summary analysis was done. Results: A total of 372 patients were identified including 1 male patient Age ranges from 21yrs to 81 yrs and mean age was 51.06 yrs. Majority of patients were Stage II (38.97%) and III (38.44%). Invasive duct carcinoma was found in 83.87% (n ¼ 312) and Invasive lobular carcinoma was 6.98% (n ¼ 26). ER, PR and Her2 status was tested only 9.6% (n ¼ 36) among all patients due to different limitations. The number of patients having biomarker test were gradually increase from 2013 to 2016 (7.04%, 5.26%, 9.52% and 22.22% respectively). Surgery was the main treatment for all patients and none of them underwent breast conserving surgery. 23.65% (n ¼ 88) of patients lost follow up for adjuvant treatment after surgery. Cyclophosphamide, Methotrexate and 5-Fluorouracil (CMF), Doxorubicin, Cyclophosphamide, AC-paclitaxel, docetaxel and capecitabine were used for chemotherapy in 76.34% (n ¼ 284). Radiotherapy combined with chemotherapy was done in 29.83% (n ¼ 111). Aromatase inhibitors mainly letrozole were used for hormonal therapy in 32.25% (n ¼ 120) of patients and 8% (n ¼ 31) were given tamoxifen. Conclusions: Breast cancer is the commonest cancer among Myanmar women. Basic and limited level therapies were provided for all patients in this hospital. However, due to misconceptions about diagnosis and treatment, limitation of access to treatment, financial difficulties, a relatively high number of patients did not take adjuvant treatment after surgery. Multi-institutions studies should be carried out to understand about current status of cancer care to support to establish successful cancer control program in Myanmar. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. to investigate the risk factors for female breast cancer in post-menopausal Pakistani population of southern Punjab. Methods: A case control study involving 250 breast cancer patients and 500 controls that screened negative for breast cancer on mammography was carried out. Information about demographic characteristics and potential risk factors for breast cancer was gathered from both groups using standard questionnaire. Logistic regression analysis was employed to determine the association of various potential risk factors with breast cancer. Results: In the multivariate logistic regression analysis, breast cancer risk was found to be significantly increased in women with age >40 years (OR ¼ 1.84, 95% CI ¼ 1.512.24), age at menarche 13 (OR ¼ 1.45, 95% CI ¼ 1.01-2.10), age at 1st live birth <20 (OR ¼ 2.73, 95% CI ¼ 1.56-4.78), no of full term pregnancies > 4 (OR ¼ 5.33, 95% CI ¼ 1.96-14.53), living in rural areas (OR ¼ 3.46, 95% CI ¼ 2.29-5.84). There was no effect of contraceptive use on risk for breast cancer (OR ¼ 0.93, 95% CI ¼ 0.48-1.72) and family history of breast cancer (OR ¼ 0.81, 95% CI ¼ 0.22 – 1.02). In addition, no significant association was found between breast cancer risk and age of menopause, lactation, parity, breastfeeding and history of spontaneous or induced abortion. Conclusions: The findings of this study suggest that age >40 years, age at menarche, age at 1st live birth and locality are significantly associated with increased breast cancer risk in post-menopausal Pakistani women in Southern Punjab. Legal entity responsible for the study: Nishtar Medical College Hospital, Multan Funding: Nishtar Medical College Hospital, Multan Disclosure: All authors have declared no conflicts of interest. 83P Breast cancer management in an Indian oncology framework: Comparison with the standard guidelines A. Sharma1, G. Parthasarathi1, C.B. Avinash2 Pharmacy Practice, JSS College of Pharmacy, Mysore, Mysore, India, 2 Medical Oncology, Bharath Hospital and Institute of Oncology, Mysore, India 1 81P Breast Self-Examination (BSE): A strategy for early detection of breast cancer in Nigeria Y.C. Adetule Surgical Nursing, University College Hospital, Ibadan, Nigeria Background: Breast Self-Examination (BSE) can be used as a strategy for early detection of breast cancer in sub-Saharan country such as Nigeria. However, the knowledge and practices of BSE among Nigerian adolescents have not been adequately investigated. Methods: A descriptive survey was used to assess the knowledge and practice of selfbreast examination among female adolescents in senior secondary in Ibadan North Local Government of Oyo State, Nigeria. The sampling technique adopted in the study was the simple random sampling. The respondents were reassured of the confidentiality of the data. The instrument used basically was self-structured questionnaire. Results: On the respondent’s knowledge of SBE before this study, only (97.3%) of the respondents have heard of self-breast examination of which the awareness was mostly related to mass media, (52.3%) knew that it is perform by female,(36.4%) knew that it should be performed monthly,(51.8%) knew that it is done after menses and (52.7%) knew that SBE should be done with the palm and minimum of three fingers. Regarding the practice of SBE (14.5%) practice it monthly, while more than half,(58.2%) have never practiced it only (11.8%) practiced it in the last 3 to 6 months and was performed before their menstrual period. Conclusions: It can be deduced that the level of awareness of Breat Self Examination(BSE) is high but the knowledge of how it should be performed is low. There is need for governments, policy makers, public health personnel especially nurses, physician, public health officers to work on strategies for increasing the practise of BSE in Nigeria. Legal entity responsible for the study: Yemisi Cecilia Adetule Funding: University College Hospital Disclosure: All authors have declared no conflicts of interest. 82P Risk factors for breast cancer: A case-control study among post-menopausal women in Pakistan 1 2 2 3 Background: A study was conducted to assess the utilization pattern of anticancer drugs and comparing it with the standard guidelines. Methods: This was a prospective study carried out for 18 months at an oncology speciality. All the newly diagnosed patients were enrolled. The relevant data was collected from medical records to evaluate the prescribing practice, patient/caregivers’ interviewed to complete any other relevant data. The prescriptions were reviewed in lieu of disease & tumor characteristics, chemotherapy selection & administration, prescribed anti-emetics in terms of selection, dose, dilution & administration to assess their compliance with the standard guidelines (NCCN). Results: 92 patients corresponding to 129 prescriptions were evaluated. The study population comprised of early disease (63%), locally advanced (17%) and metastatic (7%) based on disease & tumor characteristics. 13% patients were planned for neoadjuvant therapy. The regimen followed in all these patients was anthracycline based with/without 5-Fluorouracil (5-FU). 35% had anthracycline along with 5-FU and 65% without it. Amongst the 5-FU containing regimens 27.5% had doxorubicin and 72.5% cases had epirubicin. The prescriptions without 5-FU were added with taxanes. 80% contained paclitaxel whereas 7% had docetaxel prescribed. It was observed 26% had hormone positive disease and were planned to be prescribed with tamoxifen or anastrazole. 11% were Her2/neu positive and planned to be given trastuzumab. Although the dosing of the chemotherapeutic agents was not according to BSA for the subsequent cycles but the selection was compliant in all the cases. 22% prescriptions had administration errors where the drug was not administered as prescribed. 31% antiemetics prescriptions were in line with standards and rest were noncompliant. The noncompliance was observed in terms of selection of anti-emetics (46%); dose (31%); dilution (13%); and administration (10%). Conclusions: The drug selection was as per the standard guidelines but noncompliance was seen in its administration. There were many deviations seen in the selection of anti-emetics from the standard guidelines; maybe due to the financial constraints of the patients. Legal entity responsible for the study: Aakanksha Sharma Funding: N/A Disclosure: All authors have declared no conflicts of interest. 84P Clinical characteristics and outcomes of bilateral breast cancer in a Tunisian cohort 3 N.A. Jadoon , M. Hussain , F.U. Sulehri , A. Zafar , A. Ijaz Medicine, Hull ROyal Infirmary, Kingston Upon Hull, UK, 2Medicine, Nishtar Medical College and Hospital (NMC) Clinical Oncology, Multan, Pakistan, 3 Gastroenterology, Hull ROyal Infirmary, Kingston Upon Hull, UK 1 O. Jmour1, A. Belaid1, F. Mghirbi2, F. Benna1 1 Radiation Oncology, Institut Salah Azaı̈z, Tunis, Tunisia, 2Medical Oncology, Institut Salah Azaı̈z, Tunis, Tunisia Background: There is paucity of data on breast cancer risk factors in Asian population especially in the post menopausal group. This study was therefore carried out to determine the risk factors for breast cancer in this group. The objective of this study was Background: Bilateral breast cancer (BBC) is a particular entity requiring an appropriate care. It can be synchronous or metachronous. The aim of this study was to ix24 | abstracts Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology describe the epidemiological profile, the clinicopathological and therapeutic features of bilateral breast cancer and to evaluate their prognosis and survival. Methods: We have undertaken a monocentric retrospective study of 140 patients with BBC treated and followed at the Salah Azaiez Institute. Cases diagnosed within 6 months of diagnosis of the first breast cancer were classified as synchronous and cases diagnosed more than 6 months were classified as metachronous. Results: The frequency of BBC was 2.3%. Thirty-nine patients had metachronous cancer and 101 had synchronous one. The mean interval between the first and the second cancer was 13,5 months. The mean age was 49 years. Sixty-two percent were postmenopausal. Fourteen percent had a positive family history for breast carcinoma. Mammography showed opacity with malignant features in the contralateral breast in 46,6% of the cases. The average tumor size was 46 mm. T4 stage was found in 34.4% patients. Twenty-seven patients (19.3%) had metastatic disease at diagnosis. Bilateral surgery was performed in 73,6% whose radical one was done in 53.6% of the cases. On pathology, ductal invasive carcinoma was found in 79,3% of cases whereas lobular invasive carcinoma in 9,3%. The mean diameter of resected tumours measured by pathologists was 38.8 mm. Positive lymph nodes accounted for 62.6% of all tumors. Hormone receptor status was positive in 74% of the cases. Human epidermal growth factor receptor (HER2), was amplified in 34 of 96 tumors. Radiotherapy was delivered in 85% of patients, chemotherapy in 93.6% and hormonal treatment in 65%. The median follow-up was 59 months. The five-year overall survival was 62%. The main prognostic factors on overall survival were the clinical stage (p < 0.001), lymph node involvement (p ¼ 0.018) and the interval between the first and the contralateral cancer (p ¼ 0.012). Conclusions: Improvement of diagnosis and treatment of breast cancer should increase the incidence of BBC. Management of these cancers aims to control the disease without risking cumulative toxicity. Legal entity responsible for the study: N/A Funding: Salah Azaiz Institute Disclosure: All authors have declared no conflicts of interest. 85P Clinical characteristics and outcomes of synchronous bilateral breast cancer in a Tunisian cohort O. Jmour1, A. Belaid1, F. Mghirbi2, F. Benna1 1 Radiation Oncology, Institut Salah Azaı̈z, Tunis, Tunisia, 2Medical Oncology, Institut Salah Azaı̈z, Tunis, Tunisia Background: The incidence of synchronous bilateral breast cancer (SBBC) is comprising between 1 and 3% of all cases of breast cancers. Most studies have defined SBBC as the presentation of bilateral breast cancer within 0–6 months of each other. The aim of this study was to describe the epidemiological profile, the clinicopathological and therapeutic features of bilateral breast cancer and to evaluate their prognosis and survival. Methods: We have undertaken a monocentric retrospective study of 101 patients with SBBC treated and followed at the Salah Azaiez Institute. Cases diagnosed within 6 months of diagnosis of the first breast cancer were classified as synchronous. Results: The frequency of BBC was 1,65%. One hundred and one patients had synchronous one. The mean age was 51 years. Fifty-eight percent were postmenopausal. Eleven percent had a positive family history for breast carcinoma. Mammography showed opacity with malignant features in the contralateral breast in 55,4% of the cases. The average tumor size was 46 mm. T4 stage was found in 44,8% patients. Twenty-five (24,7%) had metastatic disease at diagnosis. Bilateral surgery was performed in 72,2% whose radical one was done in 36,6% of the cases. On pathology, ductal invasive carcinoma was found in 81,1% of cases whereas lobular invasive carcinoma in 10,9%. The mean diameter of resected tumours measured by pathologists was 31,3 mm. Positive lymph nodes accounted for 61% of all tumors. Hormone receptor status was positive in 78% of the cases. Human epidermal growth factor receptor (HER2), was amplified in 23 of 69 tumors. Radiotherapy was delivered in 77,3% of patients, chemotherapy in 87% and hormonal treatment in 73,6%. The median follow-up was 57 months. The five-year overall survival was 60%. The main prognostic factor on overall survival was the clinical stage (p < 0.001). Conclusions: The most common approach when determining adjuvant treatment for SBBC is to use the higher stage and most adverse histological characteristics of the tumors as index. Improvement of diagnosis and treatment of breast cancer should increase the incidence of SBBC. Management of these cancers aims to control the disease without risking cumulative toxicity. Legal entity responsible for the study: N/A Funding: Salah Azaiz Institute Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 86P Overview of breast cancer management: Yangon private sector cancer care S. Mon1, T.T. Aye1, M. Khine2, E.P.P. Aung2, A.S. Nyunt2, P.T. Hnin2, S.S. Htay1, N. Sein1, E. Khaing2 1 Oncology Department, Bahosi Medical Centre Bahosi Housing Complex, Yangon, Myanmar, 2Oncology, Thurein Oncology Clinic, Yangon, Myanmar Background: With the development of advanced technology in the field of oncology, breast cancer treatment becomes individualized nowadays. Breast cancer is the commonest cancer in Myanmar women. Aim of this study is to explore about breast cancer treatment in private sector cancer care in Yangon, Myanmar. Methods: Clinical data of breast cancer patients registered at 3 private clinics in Yangon, Myanmar from July 2014 to June 2016 were studied and analyzed. Results: Including 2 male breast cancer patients, a total of 488 breast cancer patients were registered. Mean age is 52.73 yrs (range 22yrs - 87yrs). 13.53% (n ¼ 66) were young age patients under age of 40. Most patients were diagnosed at Stage II ¼ 65.57% (n ¼ 320) and Stage III¼18.85% (n ¼ 92).82.5% (n ¼ 407) were investigated for biological markers (Estrogen, progesterone receptors and Her2) using immunohistochemistry method whereas 8.23% were not done the test due to financial limitations. Ki 67, P53 status were done in only 11.47% (n ¼ 56). Molecular subtypes were ER positive HER2 negative in 39.8% (n ¼ 162), Her2 positive in 37.59% (n ¼ 154) and Triple Negative Breast cancer in 17.93% (n ¼ 73).Total mastectomy and axillary clearance was done in 94.03% (n ¼ 459). Breast conserving surgery was done in 3.8% (n ¼ 15). Sentinel Lymph node Biopsy was done in 3.6% (n ¼ 18).Breast reconstruction surgery was done in 0.61% (n ¼ 3). Radiation treatment was done in 12.09% (n ¼ 59). Neoadjuvant and adjuvant chemotherapy using different regimes were done in 96.72%(n ¼ 472). Among Her2 positive patients, 27.27% (n ¼ 42) can afford for anti Her2 targeted therapy. Hormonal therapy using Tamoxifen or Aromatase Inhibitors was given to all ER positive cases depend on menopausal status. Conclusions: Total mastectomy and axillary lymph node dissection was the treatment of choice in surgical management due to patients preference and limitations to access radiation therapy. Limited number of Her2 positive patients received molecular targeted therapy due to financial difficulities. Overall, access to treatment, financial limitations and insufficient health care system are the barriers to get standard treatment in breast cancer in Myanmar. Legal entity responsible for the study: Thurein Clinic, Yangon Funding: Thurein Clinic, Yangon Disclosure: All authors have declared no conflicts of interest. 87P Therapeutic effect of harmonic scalpel versus electrocautery in axillary dissection of breast cancer W. Dong Department of Breast Surgery, Affiliated Tumor Hospital Xinjiang Medical University, Urumqi, China Background: Improving results of superiority of ultrasonic knife applied in laparoscopic surgery have led to growing acceptance of this approach as a potentially hemostatic method for “open “operation, and recently, harmonic scalpel are turn into an burgeoning tool and effective surgical instruments for sharp dissection, stanch bleeding, dissection and haemostasis in axillary dissection of breast cancer.Accumulating clinical evidence indicates that harmonic scalpel had more advantages than electrocautery in axillary dissection, however, the conclusion of superiority remains inconclusive.Therefore, we aimed to assess the utility and advantages of this instrument compared with electrocautery to perform axillary dissection. Methods: A retrospective case-control study was designed to present the therapeutic effect of two surgical instruments respectively(Harmonic scalpel vs electrocautery).The surgical and pathosis details of 23 breast cancer patients who underwent axillary dissection using the ultrasound scissors were compared with 23 breast cancer patients, matched for age, Body surface area (BSA) and stage of disease, operated by the same surgical team using electrocautery during the same period.The results were evaluated in terms of intra-operative blood loss, operating time, postoperative drain volume and drain days, wound infection, postoperative pain, mobility of the shoulder, and hospitalization stay duration. Results: There was no significant difference in the operating time between the ultrasound scissors and electrocautery group (90.22617.74 and 93.04619.41 mins, p > 0.05). The blood loss (33.04 6 18.2 ml and 89.78 6 49.14 ml, p < 0.001) and axillary total drainage volume (176.576132.30 ml and 271.57 6 136.04 ml, p < 0.001), the chest wall total drainage volume (91.73 6 60.14 ml and 130.59 6 62.59 ml, p < 0.001) were significantly lower in the harmonic scalpel group. There was a significant reduction of draining days in ultrasound scissors group(mean one and four days, respectively p < 0.05). doi:10.1093/annonc/mdw575 | ix25 abstracts Conclusions: Axillary dissection can be safely performed using ultrasound scissors with a significant reduction in blood loss, duration of drainage and hospitalization stay compared to electrocautery. Legal entity responsible for the study: Zhu Li-Ping Funding: N/A Disclosure: W. Dong: This abstract recommended by CSCO 88P Color Doppler parameters: a non invasive prognostic marker in carcinoma breast in both naive and neoadjuvant chemotherapy patients. H.B. Govardhan1, S. Pradhan2, R. Jain3, K. Ibrahim A1, P. Sridhar1 Radiation Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India, 2 Radiation Medicine and Radiotherapy, Institute of Medical Sciences, Banaras Hindu University, IMS-BHU, Varanasi, India, 3Radiation Oncology, Pt.J.N.M.Medical College Raipur, Raipur, India 1 Annals of Oncology Results: Of 73 patients who participated in POTENT study, 38 were assigned to S-1 group and 37 participated in this study. Evaluable answers to questionnaire survey were collected from 30 patients. The proportion of patients who selected GN after taking two types of forms, was 36.7% (11/30). In all patients, the VAS scores compared between GN and OD groups were as following. DIT; 41.264.8 vs 23.564.2 (p ¼ 0.007), taste; 45.065.3 vs 33.366.2 (p ¼ 0.122), discomfort; 22.764.4 vs 19.764.4 (p ¼ 0.538), DOS; 62.764.1 vs 72.463.9, (p ¼ 0.077). Therefore, GN were significantly more difficulty in taking, whereas OD were likely more satisfactory. Moreover, a significant reduction in DIT was achieved in patients who switched from GN to OD (40.766.2 to 23.265.9, p ¼ 0.035) and their satisfaction was likely elevated (62.765.7 to 76.364.9, p ¼ 0.064). Conclusions: OD were easier or more satisfactory to take than GN. However, some patients preferred GN rather than OD. We recommend S-1 should be initially administered with OD, then switched to GN in accordance with patients’ preference. Legal entity responsible for the study: Yoshinori Ito Funding: N/A Disclosure: All authors have declared no conflicts of interest. 90P Background: To investigate the role of color Doppler parameters in carcinoma breast as non invasive prognostic marker. Methods: A total of 92 patients o carcinoma of breast who are all candidate for surgery were underwent color Doppler study, RI (resistivity index), PI(pulsatality Index) and Vmax were documented. All these Doppler parameters were graded as per standard guideline(grade1-4). These color dopplers grading were correlated with histopathological findings like tumor size, lymph node, histopathological grade. On follow up data, the color Doppler grades were also compared and correlated with overall survival and disease free survival at 5 years. Appropriate statistics were used or analysis. Results: Out of 92 patients all patients were able to correlate the Doppler parameters (PI, RI, VMax) with histopathological parameters(size, Lymph node and grade). Out o 92 patients 30 patients were received neoadjuvant chemotherapy. For all patients, the results were already presented elsewhere, now we are concentrating on patients with NACT. For follow up data only 56 patients were available to calculate overall survival and DFS. PI were correlated with tumor size, lymph node number, grade were- 0.675 (p < 0.05): 0.412(p > 0.05): 0.518(p < 0.05) respectively. For RI and vmax the correlations were: 0.712(p < 0.05), 0.617(p < 0.05) and 0.778(p < 0.05) for RI: 0.123(p > 0.05), 0.487(p > 0.05) and 0.312(p > 0.05) for Vmax, respectively for tumor size, lymph node and tumor grade. The 5 years OS and DFS for RI and Vmax were statistically significant and were compared with the other prognostic markers of breast cancer, like size of tumor and lymph node and grade of the tumor. Conclusions: Color Doppler can be one of the prognostic factor in carcinoma breast in both naive and patients undergoing neoadjuvant chemotherapy. Due to its non invasiveness, and its predictiveness it is very important tool in patients undergoing or neoadjuvant chemotherapy. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 89P Questionnaire survey on patients’ preference for orally disintegrating tablets or granules of S-1 in postoperative adjuvant treatment for breast cancer I. Fukada1, Y. Ito1, T. Shibayama1, K. Kobayashi1, N. Teruya2, S. Takahashi3, R. Horii4, F. Akiyama5, T. Iwase2, M. Toi6, S. Ohno 7 Breast Medical Oncology, Cancer Institute Hospital of JFCR, Tokyo, Japan, 1 2 Breast Surgical Oncology, Cancer Institute Hospital of JFCR, Tokyo, Japan, 3 Medical Oncology, Cancer Institute Hospital of JFCR, Tokyo, Japan, 4 Department of Pathology, Cancer Institute Hospital of JFCR, Tokyo, Japan, 5 Department of Pathology, Cancer Institute of JFCR, Tokyo, Japan, 6Breast Cancer Unit, Kyoto University Hospital, Kyoto, Japan, 7Breast Oncology Center, Cancer Institute Hospital of JFCR, Tokyo, Japan Prognostic value of vitamin-D level in non-metastatic breast cancer patients in Saudi Arabia S. Elsamany1, A. Alzahrani2, O. Elemam1, S. Elmorsy2, N. Abo Hashish3 Oncology, Oncology Centre Mansura University, Dakahlia, Egypt, 2Oncology, King Abdullah Medical City, Mecca, Saudi Arabia, 3Research, King Abdullah Medical City, Mecca, Saudi Arabia 1 Background: Deficiency of vitamin-D was associated with poor outcome in several studies across different tumour types. The present study aims to assess the prevalence and prognostic value of vitamin D deficiency among breast cancer patients in a single institution in Saudi Arabia. Methods: In this retrospective study, we screened patients who presented with nonmetastatic breast cancer to King Abdullah Medical City, Saudi Arabia from June 2011 to December 2014. We checked baseline vitamin-D level before starting systemic therapy in addition to other clinicopathological factors. Low vitamin-D was defined as vitamin-D level less than 30 ng/ml. The relations of vitamin-D level with clinicopathological factors were assessed using independent samples t-test. Chi-square test was used to assess the correlation of those variables with relapse risk while Cox regression analysis was used to check for the relation of vitamin- D level as a continuous variable with the risk of relapse. Results: We screened 286 patients with non-metastatic breast cancer. Baseline vitaminD levels were available for 141 patients. Mean and median vitamin-D levels were 16.96 9.1 ng/ml and 15.9 ng/ml, respectively. Mean vitamin-D level was significantly lower in ER-negative compared to ER-positive patients (14.267.1 vs. 18.669.7 ng/ml respectively, p ¼ 0.007), in PR-negative compared to PR-positive patients (14.5 66.9 vs. 18.8 69.9 ng/ml respectively, p ¼ 0.006) and in patients with lymphovascular invasion (LVI) compared to those with no LVI (15.4 68.3 vs. 21.26 9.8 ng/ml, p ¼ 0.001). Vitamin-D level as a continuous variable was not associated with the risk of disease relapse (hazard ratio¼ 0.99; 95% Confidence interval: 0.94-1.05, p ¼ 0.69). Using chisquare test, LVI (p ¼ 0.021), ER-negative (p < 0.00001), PR-negative phenotype (p < 0.00001) and higher clinical stage at diagnosis (p < 0.00001), were significantly associated with the risk of relapse. Conclusions: Low vitamin- D level was prevalent among the studied breast cancer patients. Low vitamin- D level was associated with ER/PR-negative phenotype and with positive LVI. Baseline vitamin- D level was not linked with the risk of disease relapse. Legal entity responsible for the study: King Abdullah Medical City, Saudi Arabia Funding: King Abdullah Medical City, Saudi Arabia Disclosure: All authors have declared no conflicts of interest. 91P Efficacy of gabapentin for prevention of paclitaxel induced neuropathy: randomized double blind, phase 3 trial M. Zare1, M. Aghili2, B. Kalaghchi2, H. Dehghan Manshadi3, E. Esmati2 Radiation Oncology, Iran University of Medical Sciences, Tehran, Iran, 2 Radiation Oncology, Cancer Institute, Tehran, Iran, 3Clinical Oncology, Shohadaye 7 Tir, Tehran, Iran 1 Background: No study has investigated patients’ preference for orally disintegrating tablets (OD) or granules (GN) in patients with breast cancer. In a phase III randomized study of adjuvant one-year treatment with S-1 (tegafur/gimeracil/oteracil) for estrogenreceptor positive, HER2-negative breast cancer (POTENT study), we prospectively compared patients’ preference on two types of dosage forms. Methods: The subjects were patients assigned to S-1 group in our hospital based on their consent participating the POTENT study. In those registered with even numbers, OD were administered on cycle 1, 2, then GN on cycle 3, 4. In those registered with odd numbers, GN were administered on cycle 1, 2, then OD on cycle 3, 4. Subsequently, patients selected dosage form based on their preference. Primary endpoint was the proportion of patients who selected GN. As a secondary endpoint, the impressions regarding each types were evaluated using the 100-mm Visual Analog Scale (VAS); difficulty in taking (DIT), taste, discomfort and degree of satisfaction (DOS). VAS scores were expressed as the mean6standard error. The Mann-Whitney U-test was used statistically. ix26 | abstracts Background: Paclitaxel is an antineoplastic agent; peripheral neuropathy and neutropenia are the major side effects of this drug. Despite multiple studies there is still no consensus on how to prevent them. Some studies show this neuropathy ranging from 40% to 70% for grade 1 and 2, and 5% to 20% for grade 3 and 4. Gabapentin is an antiepileptic drug inducing a moderate and statistically significant relief of pain. Methods: Before initiating paclitaxel for patients, we assessed their sural and proneal nerve with nerve conduction velocitiy (NCV) testing. This assessment was repeated 6 weeks after completion of CTh. For objective assessment we took history and physical exams according to CTCA4 after each cycle of paclitaxel. We asked patients about Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology numbness, pain, parenthesis and tingling and scored them according to CTCA4; also we asked them about adverse effects of gabapenthin. Results: The mean age of the gabapentin group was 46.40 (SD ¼ 7.09) and for the placebo group was 43.70 (SD ¼ 8.70). Although most of the patients in the gabapentin group had grade 1 neuropathy, none of them experienced grade 3 neuropathy; in contrast, most patients in the control group had grade 2 or 3 neuropathy. In contrast to placebo group, NCV did not show any significant change during treatment in the gabapentin group; this difference was significant in sural and proneal nerve (p ¼ 0.003; p ¼ 0.008). Conclusions: Paclitaxel is one of the most important drugs used in breast cancer, and peripheral neuropathy is one of the most common side effects of this drug. In one study conducted by Postma et al (Ann Oncol 1995; 6: 489) they studied patients who received paclitaxel at different doses - 135 mg/m2 175 mg/m2 and 250 mg /m2 – and reported neuropathy in each group as 50% ,75% and 100%, respectively. Gabapentin is an anticonvulsant drug that can prevent axonal destruction and death. in another phase 3 clinical trial conducted by Rao et al. published in Cancer (2007; 110: 2110) they failed to demonstrate any benefit of using gabapentin for treatment of any chemotherapyinduced neuropathy but in our trial we use it as protector. In another study published in the European Journal of Cancer in 2003 Foladore et al. (ASCO Annual meeting abstract) studied protective effect of gabapentin in patients receiving cisplatin, oxaliplatin and paclitaxel they concluded that gabapentin can decrease grade 1 and 2 neuropathy from 40% -70% to 25%. Clinical trial indentification: This randomized, double-blind, placebo-controlled phase 3 trial was conducted in cancer institute, Tehran university between 2009 to 2011. The protocol and informed consent documentation were reviewed by ethics committee of Tehran university. Legal entity responsible for the study: Tehran University of Medical Sciences Funding: Tehran University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. 92P Knowledge, attitude and prevention practice about breast cancer among female nursing students in University of Nursing (Yangon), Myanmar T.T. Aye, S. Mon Medical Oncology, Bahosi Medical Centre Bahosi Housing Complex, Yangon, Myanmar 93P R. Kirubakaran, T.C. Jia Department of Pharmacy, Sultan Abdul Halim Hospital, Sungai Petani, Malaysia Background: Breast cancer is the commonest cancer among women worldwide. About one in nineteen women in Malaysia are at risk, compared to one in eight in Europe and the United States. Objectives: To assess patients’ knowledge on risk factors, symptoms and methods of screening of breast cancer. To determine their perception towards the disease treatment outcomes. Methods: A cross-sectional survey using validated self-administered questionnaire was conducted among 119 consecutive surgical female patients admitted from 1st of September 2015 to 8th of October 2015 in Hospital Sultan Abdul Halim, Kedah. Patients were required to answer 8 questions on demographic characteristics, 22 questions on knowledge of breast cancer and 5 questions related to their perception towards breast cancer treatment outcomes. Data was analyzed using General linear regression and Spearman’s correlation with Statistical Package for Social Science (SPSS) version 20. Results: Mean(SD) age was 40.6(15.1) years and majority of the patients were Malay, 106(89.1%). Mean score for general knowledge, risk factors and symptoms of breast cancer were 50.2(24.0%), 43.0(22.9%) and 64.4(28.4%) respectively. Mean total knowledge score was 52.1(19.7%). 80(67.2%) and 55(46.2%) of patients were aware of breast self examination and clinical breast examination recommendations respectively. Generally, patients had positive perceptions towards breast cancer treatment outcomes. However, majority (59.7%) think that it is a long and painful process. Knowledge was significantly better among married patients with spouse (p ¼ 0.046), those with personal history of breast cancer (p ¼ 0.022) and with personal monthly income (p ¼ 0.001) with the coefficient of determination, R2¼0.16. Spearman’s correlation test showed a significant positive relationship between monthly personal income and breast cancer awareness (r ¼ 0.343, p < 0.001). Conclusions: Overall, awareness on breast cancer among patients was poor. Thus, there is a need for awareness programs to educate women about breast cancer and to promote the early detection of breast cancer. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 94P Background: Breast cancer is one of the most dreaded conditions among women both in developed and developing countries and recent global cancer statistics indicate that its incidence is rising at a faster rate in populations of developing countries. This study is conducted to assess the knowledge, attitude and prevention practice regarding breast cancer among female nursing students as they will be front runners to educate and disseminate health knowledge among public in their future professional life which may lead to early detection and effective treatment of breast cancer. Methods: A cross-sectional descriptive questionnaire study was conducted on a total of 248 female nursing students (122 first year students and 126 fourth year students) in University of Nursing (Yangon), Myanmar. Results: Mean age of students was 18.33 6 1.7 year (Range: 16-22 years) and majority was Bamar (80%). Among participants, 17% had family history of malignancy and 3% had past history of breast lumps. Regarding knowledge, 60% students knew that breast cancer can occur only in women and ageing(34%), obesity(36%), nulliparous (57%) and late bearing of first child(>30 years old)(50%) were known as risk factors. About more than 50% of subjects knew the symptoms of breast cancer and 48%, 37% and 49% respectively were aware of correct timing, frequency and method of breast self examination. However, only about 30% of students had the correct knowledge concerning with clinical breast examination and only 11% knew the age at mammogram should be started. Although 60% of studied subjects had positive attitude towards the early detection of breast cancer, 47% practiced breast self examination (BSE). Of those who practiced BSE, only minority performed regularly (38%) and with correct frequency (50%). Conclusions: These female nursing students who are expected to act as role models and educate the public had limited level of knowledge about breast cancer and practice of breast cancer screening. This study highlighted that there is still need for promoting nursing education programme about breast cancer and its screening practice among nursing students in Myanmar. Legal entity responsible for the study: Bahosi Hospital, Yangon, Myanmar Funding: N/A Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 Awareness of breast cancer among surgical female inpatients in Kedah Influence of different treatment planning techniques on radiation doses to the heart, left anterior descending coronary artery and lungs in the radiotherapy of left-sided breast cancer patients F. Hadjilooei1, P. Haddad1, B. Kalaghchi1, F. Amouzgar Hashemi1, M. Esfahani2, H. Nedaie2, S. Shahriaran3, M. Babaei4, F. Farhan4 1 Radiation Oncology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran, 2Radiotherapy Physics Department, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran, 3Radiology Department, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran, 4Radiation Oncology Department, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran Background: Breast-conserving surgery (BCS) followed by radiotherapy (RT) to the breast is now an acceptable standard of care for the majority of women with early-stage breast cancer. But evidence has long been accumulating that RT doses to the heart can result in premature ischemic heart disease. In this study 3 different RT techniques were compared for heart, left anterior descending coronary artery (LAD) and lung doses in left breast cancer patients after breast-conserving surgery. Methods: Three different plans were designed for each patient using conventional tangential fields, 6 þ 18 MV combination beams, and filed-in-field (FIF) technique. These were compared in terms of doses to the planning target volume (PTV), ipsilateral lung, heart and LAD. Results: Forty left breast cancer patients were included in this study. Mean PTV V95% was 95.74% for conventional, 90.45% for FIF and 87.89% for 6 þ 18 MV (p < 0.05). Mean left lung dose was 11.22 Gy for FIF, 12.25 Gy for 6 þ 18 MV and 12.95 Gy for conventional (p < 0.05). Mean heart dose was 4.52 Gy for FIF, 4.85 Gy for 6 þ 18 MV and 5.13 Gy for conventional (p < 0.05). Mean heart V5Gy was 11.80%, 12.02% and 13.23% (p < 0.05), mean heart V25Gy was 6.1%, 6.35% and 6.65% (p < 0.05), and mean D2% for LAD was 40.06, 43.43 and 45.25 Gy (p < 0.01) in FIF, 6 þ 18 MV and conventional techniques, respectively. Conclusions: The results of our study indicated that the FIF and 6 þ 18 MV combination techniques significantly reduced the doses received by the heart, LAD and left lung compared to conventional tangential fields, while FIF was superior in general to 6 þ 18 MV considering the above variables. The lower doses to the organs at risk were achieved in these plans with a small but statistically significant loss in PTV coverage. doi:10.1093/annonc/mdw575 | ix27 abstracts Clinical trial indentification: 94-02-207-29322 Tehran University of Medical Sciences Legal entity responsible for the study: Radiation Oncology Research Center, Tehran University of Medical Sciences Funding: Tehran University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. 95P Radiotherapy (RT) for breast cancer patients- clinical implementation of the first ever Tomotherapy-H in a tertiary cancer centre in India N. Hanumanthappa1, P. Krishnamurthy2, J. Amalraj2, P. Anchaneyan2, A.B.S. Kumar1, S. Ramamurthy1 1 Radiation Oncology, HCG Bangalore Institute of Oncology Speciality Centre, Bangalore, India, 2Radiation Physics, HCG Bangalore Institute of Oncology Speciality Centre, Bangalore, India Background: The first ever Tomotherapy-H system in India became operational in Feb 2016 in our hospital, Health care global enterprises, a tertiary level cancer care centre. In order to implement Tomotherapy as a routine technique to treat breast cancers we under took dosimetric comparison of helical Tomotherapy plans and five field forward planning intensity modulated radiotherapy (IMRT) plans. Methods: We compared the Helical Tomotherapy plans with IMRT plans of the first 10 patients with early breast cancer who underwent adjuvant RT using helical Tomotherapy technique in our centre between February 2016 and June 2016. The treatment planning objectives were to cover 95% of the planning target volume (PTV) using a 95% isodose (V95 >/¼ 95%), with a minimum of 90% isodose covering 100% of PTV (V100 >/¼ 90%) and no more than 10% of PTV to receive 110% (V110 <10%). The heart and lungs were contoured as organs at risk (OAR) and doses received were recorded in both the planning techniques. Results: All patients were females with four right and six left sided cancers. Seven patients had undergone breast conserving surgery and three had mastectomy. When we compared the forward planning IMRT plans with Helical Tomotherapy plans, we found that the advantage of using Helical Tomotherapy included significantly better coverage for V95 (p < 0.000), V100 (p < 0.000) and median V110 was 0.06% and 0.14% in Helical Tomotherapy and IMRT plans respectively. Helical Tomotherapy plans had lower dose to ipsilateral lung (V35 P < 0.01) and lower median dose to the heart (Tomotherapy¼8.2 and IMRT¼9Gy). There was improved coverage of the planning target volume, including the regional nodes, without any field junction problems. None of the patients had any more than grade 1 skin toxicity and grade 1 oesophagitis. Conclusions: Helical Tomotherapy, compared to forward planning IMRT for breast cancer treatment, demonstrated better target coverage and sparing of OARs. The treatment was well tolerated with minimal toxicity. Long term toxicity is yet to be established by continued follow up of these patients in late side effects clinics. Legal entity responsible for the study: Health Care Global Enterprises Funding: Health Care Global Enterprises Disclosure: All authors have declared no conflicts of interest. 96P Prevalence of hypothyroidism among breast cancer patients treated with radiation to the supraclavicular field: A single center survey Y. Kikawa1, H. Kato1, Y. Kosaka2, K. Hashimoto1, E. Hohokabe1, S. Takebe1, K. Ueki2, K. Ogura2, T. Imagunbai2, M. Kokubo2 1 Breast Surgery, Kobe City Medical Center General Hospital, Kobe, Japan, 2 Radiation Oncology, Kobe City Medical Center General Hospital, Kobe, Japan Background: Radiation-induced hypothyroidism (RIHT) is common complication of head and neck cancer or Hodgkin disease treated with radiation to the thyroid region. However, the effect of radiation on the thyroid in breast cancer patients who received a radiation therapy to the supraclavicular (SC) field is unknown. We evaluated the prevalence of hypothyroidism (HT) in these patients. Methods: Between April 2007 and May 2016, consecutive patients with invasive breast cancer who received SC radiation in Kobe City Medical Center General Hospital were recruited. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), antithyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb) were investigated during the period of April to August 2016. Based on the radiation planning CT-images of each patient, the volume of the thyroid gland was calculated and dosevolume parameters were estimated. The primary endpoint was the prevalence of HT as determined by a high serum level of TSH and low serum level of fT4. Secondary endpoints included the prevalence of subclinical HT as determined by a high serum level of TSH and normal level of fT4. Results: A total of 68 consecutive patients were screened. Among these patients, 26 were excluded from evaluation (10 patients died, 6 had a history of previous thyroid disease, 10 were lost to follow up) and blood samples were taken in 42 patients. One (2.4%) and ix28 | abstracts Annals of Oncology six (14.3%) of these patients had HT and subclinical HT, respectively, with a mean TSH level of 8.3 mU/ml. On univariate analysis, a possible predictive factor of HT and subclinical HT was a thyroid volume < 8 cm3 (OR 6.44, 95% CI 1.13-36.6), in contrast, age, dose-volume parameters, TgAb positivity or TPOAb positivity and follow-up time were not associated with HT or subclinical HT. Conclusions: The prevalence of HT in Japanese breast cancer patients treated with radiation to the SC region is relatively low compared with that in head and neck cancer and Hodgkin disease patients. Although thyroid volume appeared to be a predictive marker of HT or subclinical HT in this cohort, further prospective evaluation is needed. Clinical trial indentification: UMIN000022526 release date: June 1, 2016 Legal entity responsible for the study: Kobe City Medical Center General Hospital Funding: Kobe City Medical Center General Hospital Disclosure: All authors have declared no conflicts of interest. 97P Cardiac arrhythmia is highly associated with breast cancer compared to benign breast disease S.P. Jung1, J.W. Bae1, S-K. Oh2, J-I. Choi2, Y-H. Kim2 Surgery, Korea University Anam Hospital, Seoul, Republic of Korea, 2Internal Medicine, Korea University Anam Hospital, Seoul, Republic of Korea 1 Background: There have been reported that cancers and the cardiovascular system share common pathways, however, we do not fully understand the mechanism. Breast cancer also has been known to associate with cardiovascular disorders, including heart failure or cardiotoxicity related to chemotherapy. Therefore, we evaluated whether breast cancer, a chest wall disease, is associated with cardiac disorder. Methods: Six hundred sixty eight patients who underwent sonography guided breast core biopsy from 2011 to 2013 were studied. All baseline 12-lead electrocardiogram (ECG) were assessed in 467 patients diagnosed with breast cancer (right, n ¼ 225; left, n ¼ 242) compared to 201 patients diagnosed with benign breast disease, as a control group. ECG parameter was also analyzed according to the position of malignancy. Twenty-four hours Holter ECGs were conducted in patients with abnormal ECG and/or symptom. Results: All of patients were women and mean age of patients was 50.7 years. There were no difference in heart rate, QRS axis, bundle branch pattern, QRS duration, corrected QT interval, ST-segment change between two group. PR interval was significantly prolonged in the cancer group compared to benign group (155 ms vs. 149 ms, p ¼ 0.001), however there was no significant difference in PR interval between patient with right breast cancer and those with left breast cancer (155ms vs 154ms, p ¼ 0.768). In ECGs, ventricular premature complex (VPC) and atrial premature complex (APC) were documented only in breast cancer group (VPC, 0.64%; APC, 0.64%). Holter was conducted in 17 patients (cancer, n ¼ 9, vs. benign disease, n ¼ 8). Occasional APCs occurred more often in cancer group (66.7%, vs. 12.5%, p ¼ 0.05). Conclusions: This study showed that PR interval on ECGs was significantly prolonged and APCs was more prevalent in patients with breast cancer compared to those with benign breast disease before treatment. These findings suggest that breast cancer may be associated with the increase risk of arrhythmia. Therefore, clinicians should incorporate cardio-oncology practice from diagnosis to treatment to detect the cardiotoxicity of drugs and to observe possible cardiovascular or cardiometabolic benefits. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 98P Seaweed extract and fucoidan on breast cancer cell proliferation S.H. Chavoshi, M. Chavoshi Internal Medicine, Shahid Ghazi Medical Center, Tabriz University of Medical Sciences, Tabriz, Iran Background: Breast cancer (BC) is the most common malignancy among women in different societies. Several studies on interactive effect of marine algae extracts and its active ingredient in fucoidan has been shown to control cell division in BC cells in vitro. In this article, we aimed to review the role seaweed extract and fucoidan on BC cells proliferation. Methods: In this review, original and reviews studies published from 2006 to 2013 were summarized through PubMed, Google Scholar, Science Direct an Medline by searching for marine algae, Fucoidan and apoptosis as key words. Results: Fucoidan, a sulfated polysaccharide compounds derived from brown algae and marineInvertebrates, are actively studied for some curative and preventive biological activities, such as anti-tumor activity in cancer. These agents have shown anticancer properties in breast, lung, and blood cancer cells. Seaweed extract and Fucoidan inhibited the proliferation of human cancer cells in normal human epidermal cells. It is effective in regulating the expression of C-MYC, cyclin D1, SURVIVIN genes and Volume 27 | Supplement 9 | December 2016 Annals of Oncology consequently the expression of these gene where down regulated. It seems that an intraperitoneal injection of Fucoidan, in animal models of BCreduce volume and weight of tumor. Studies show that after treatment by Fucoidan, cytochrom C releases from the mitochondria to the cytosol, and activates caspase 3 protein.Fucoidan might also induced apoptosis by reducing the cellular capacity through the reduction of cell glutathione capacity. Studies have showed that Fucoidan, inhibited cancer cells growth in G1phase of cell cycle, as well. Volume 27 | Supplement 9 | December 2016 abstracts Conclusions: According to studies, marine algae extract and Fucoidan provide inhibitory effects on the growth and proliferation of breast cancer cells. Fucoidan could attribute in a prevention and also might considered as effective factor in chemothrepy. Legal entity responsible for the study: Tabriz University of Medical Sciences Funding: Tabriz University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. doi:10.1093/annonc/mdw575 | ix29 Annals of Oncology 27 (Supplement 9): ix30–ix34, 2016 doi:10.1093/annonc/mdw576 Breast cancer, locally advanced 99O_PR Prediction of relapse in patients with locally advanced breast cancer after neoadjuvant treatment abstracts O. Aseyev, L. Simmonds, M. Gertler, S. Verma Medical Oncology, The Ottawa Hospital Regional Cancer Centre, Ottawa, ON, Canada Background: Despite advances in cancer treatment, over 25% of patients (pts) with locally advanced breast cancer (LABC) relapse during first 5 years after treatment. The primary objective was to construct a prediction tool for risk of relapse in patients with LABC after neoadjuvant therapy. Methods: This was single center, retrospective study of 546 patients with LABC who received neoadjuvant chemotherapy at the Ottawa Hospital Cancer Center between 2005 and 2015. Median follow-up was 49 months. The following data collected: demographics, tumor size, nodal and receptor status, grade, HER-2, stage of disease, cancer treatment and clinical outcomes. Primary endpoints were local and/or distant disease recurrence rate during first 5 years and time to relapse during the first 5 years. A prediction tool was devised based on the Cox regression model. Results: The recurrence rate during first 5 years of follow up was 17.3% (local relapse – 3.2%, distant relapse – 13.2%, local þ distant relapse – 0.9%).Over 60 variables were included in primary analysis. Cox regression proportional hazards model analysis resulted in only 5 factors with significant influence on risk of relapse during first 5 years of follow up. Risk factors and their risk prediction value are: 1) residual disease (yes- 4; no-0), (HR ¼ 4.25; p-value¼0.000), 2) lymph nodes status (positive-3; negative-0), (HR ¼ 2.27; p-value¼0.006), 3) Inflammatory histology (yes-2; no-0), (HR ¼ 1.90; pvalue¼0.003) 4) estrogen receptors status (positive-2; negative-0), (HR ¼ 2.07; pvalue¼0.001), 5) Adjuvant radiotherapy (yes-0; no-1), (HR ¼ 1.76; p-value¼0.036). Internal validation of proposed model was performed. ROC analysis of the proposed model revealed a sensitivity of 75%. According to this simple RP score, patients can be classified into to three groups (RP score – 0-5; 6-7; 8-12). Risk of relapse was 7 times higher in patients with RP Score 8-12 vs patients with score 0-5 (p-value<0.0001). Conclusions: Our prognostic tool based on 5 risk factors can be used to predict risk of relapse after neoadjuvant treatment with a sensitivity of 75%. Patients with high risk may require additional treatment and/or more active follow-up strategies and this simple model may be used to design unique studies in LABC based on RP score. Legal entity responsible for the study: The University of Ottawa Funding: The Ottawa Hospital Cancer Centre Disclosure: All authors have declared no conflicts of interest. 100P Phase III of study of docetaxel and carboplatin with or without doxorubicin hydrochloride and cyclophosphamide in treating women with triple negative breast cancer S. Najafi1, M. Payandeh2, M. Sadeghi3, F. Zahra Shojaiyan1, F. Abbasvandi1, V. Shafahi1 1 Medical Oncology, Iranian Centre for Breast Cancer (ICBC), Tehran, Iran, 2 Medical Oncology, KUMS Kermanshah University, Kermanshah, Iran, 3Medical Biology Research Center, KUMS Kermanshah University, Kermanshah, Iran Background: A combination of docetaxel and carboplatin with or without doxorubicin hydrochloride and cyclophosphamide is one of the most effective front-line therapies to triple negative breast cancer. The aim of this trial was to evaluate overall survival (OS), progression free survival (PFS) and toxicity of docetaxel and carboplatin compared to docetaxel and carboplatin with doxorubicin hydrochloride and cyclophosphamide in triple negative patients with Iranian ethnicity. Methods: In a phase III trial, patients with previously untreated triple negative were randomly assigned by using docetaxel 70 mg/m2 and Carboplatin 7 AUS every three weeks with granulocyte colony-stimulating factor (G-CSF) for 6 course (Arm A) or Doxorubicin Hydrochloride 60 mg/m2 and Cyclophosphamide 600mg/m2 every three weeks with G-CSF for 4 course followed by docetaxel 70 mg/m2 and Carboplatin 7 AUS every three weeks with G-CSF for 4 course (Arm B). Results: A total of 119 patients were randomly enrolled in our study (60 patients in Arm A and 59 patients in Arm B), between 2010 and 2015. The mean follow-up was 43 months at the time of treatment analysis. The 2-year and 5-year PFS rates for Arm A were 92.7% vs. 85% and for Arm B were 82.6% vs. 64.4%. The 2-year and 5-year OS rates for Arm A were 96.5% vs. 91.7% and for Arm B were 90.5% vs. 81.3%. The 5-year OS in arm A was better than arm B, but the difference was no significant. Also, there was a significant difference for the 5-year PFS in the two arms, arm A had less progression. There was no significant difference between adverse events with the two regimens. Conclusions: In our research, less progression was found with Arm A as compared to Arm B. Therefore, adding of doxorubicin hydrochloride and cyclophosphamide to chemotherapy regimen increase the progression. Legal entity responsible for the study: Iranian Centre for Breast Cancer Funding: Iranian Centre for Breast Cancer Disclosure: All authors have declared no conflicts of interest. 101P Neoadjuvant chemotherapy for locally advanced breast cancer Y. Fomenko1, V. Sirota1, U. Bitz2, S. Zhumakaeva1, I. Omarova3, N. Kabildina1 Department of Oncology, Karaganda State Medical Academy, Karaganda, €matologie, Onkologie und Tumorimmunologie, Helios Kazakhstan, 2Klinik für Ha Klinikum Berlin Buch, Berlin, Germany, 3Department of chemotherapy, Karaganda Regional Cancer Center, Karaganda, Kazakhstan 1 Background: Neoadjuvant chemotherapy (CTX) is a standard therapy in locally advanced breast cancer. Arglabin is a sesquiterpene gamma-lactone isolated from Artemisia glabella, a species of wormwood endemic to the Karaganda region of Kazakhstan. Methods: 93 patients with locally advanced breast cancer (T2N1-2M0, T3N0-2M0) at the age from 30 to 75 years were included in the trial. All patients were randomized into 3 groups: The control group (n ¼ 36) received 4 courses of neoadjuvant CTX according to AC-protocol (doxorubicin 50 mg/m2, cyclophosphan-500 mg/m2 on day 1, repeated every three weeks) followed by radical mastectomy, 4 courses of adjuvant chemotherapy (AC), radiotherapy and hormone therapy if indicated. Investigative group 1 (n ¼ 30) received the same chemotherapy but in combination with Arglabin at a dose of 370 mg/ m2 for 7 days. Investigative group 2 (n ¼ 27) received Arglabin as monotherapy. Efficacy of the combined treatment was estimated by standard criteria of WHO. Results: A complete response of a tumor was not observed in any patient. Partial responses were observed in 58,3% of patients in the control group, in 63,3% in investigative group 1 and 25,9% in investigative group 2 (p 0,05), stable disease was diagnosed in 38,9%, 33,3% and 51,9% (p 0,05). The axillary lymph node metastasis response in patients after neoadjuvant therapy was 39.6% in the control group, 63.7% in investigative group 1(p 0,05) and 2,9% in investigative group 2 (p 0.05). In the control group, tumor regression grade 3 and 4 were 25% of patients, 33.3% were after neoadjuvant chemotherapy AC þ Arglabin and 14.8% after Arglabin monotherapy. Conclusions: Addition of Arglabin to AC-protocol in neoadjuvant chemotherapy does not improve tumor response rates. Legal entity responsible for the study: Karaganda State Medical University Funding: Karaganda State Medical University Disclosure: All authors have declared no conflicts of interest. 102P Adriamycin/taxanes based neoadjuvant chemotherapy in advanced non-metastatic breast cancer – A single institute experience H. Yasmeen, A.I. Masood Radiation Oncology, Nishter Hospital, Multan, Pakistan Background: Pakistan has the highest rate of breast cancer for any South Asian population and majority of patients present with locally advanced or metastatic disease. We report on response and survival of primary locally advanced non-metastatic breast cancer in women treated with neoadjuvant Adriamycin/Taxanes (AT) based regimens at our institute. Methods: Between 2010 to 2015, we retrospectively identified 417 women with pathologically confirmed locally advanced breast cancer. All patients received neoadjuvant chemotherapy with AT based regimen followed by surgery. Median age was 46 years (range 15-69 years). AJCC stage; stage II 56%, stage III 44%. Axillary nodes were palpable in 76% of the patients at presentation. Histological sub-types were infiltrating ductal carcinoma 94%, infiltrating lobular carcinoma 4% and others 2% respectively. Pathological grade was I/II in 48% and grade III 52% of the patients. ER, PR, and Her2-neu receptors were positive in 44%, 40% and 24% respectively. 26% of the C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts Annals of Oncology patients had triple negative breast cancer. Post operative radiotherapy was delivered to 91% of the patients. Patients with positive ER/PR receptors also received hormonal manipulation. Results: Following neo-adjuvant chemotherapy, pathological response was; complete response (CR) 14%, partial response 21%, stable disease 52% and progressive disease in 13% of the patients respectively. Breast conservation was possible in 32% of the patients. The 5 year overall survival (OS) and disease free survival (DFS) in patients with CR was 77% and 81% respectively. The 5 year OS and DFS in patients without CR was 46% and 42% respectively. On multivariate analysis T stage (p ¼ 0.001) and response to neoadjuvant chemotherapy (p ¼ 0.001) were found to be independent predictors for OS and DFS. Conclusions: Pathological response to neoadjuvant chemotherapy is a predictor of long term survival. Chemotherapy regimens with high response rates merit evaluation in randomized trials to improve outcome in locally advanced breast cancer. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 103P A prospective study on 70 patients with neo-adjuvant chemotherapy in locally advanced breast cancer (LABC) M.A. Sumon1, A. Ahsan2, A.K. Uddin3 1 Clinical Oncology, Kurmitola General Hospital, Dhaka, Bangladesh, 2Clinical Oncology, Shaheed Suhrawardy Medical College (ShSMC), Dhaka, Bangladesh, 3Radiation Oncology, United Hospital Ltd, Dhaka, Bangladesh Background: The purpose of our study is to assess the pathologic response of Neoadjuvant Chemotherapy (NACT) in locally advanced breast cancer (LABC) patients in a developing country like Bangladesh. Methods: 70 women were enrolled in the study during the period from Jan1997 to Dec 2015. All patients received six cycles NACT with FAC (5 Flurouracil 500mg/m2, Adriamycin 50mg/m2, Cylophosphamide500mg/m2 & docetaxel75mg/m2) followed by simple mastectomy & axillary dissection and radiotherapy. Surgery was undertaken between 4 to 6 weeks after the last chemotherapy and tumor specimens were examined for the presence of residual tumor. Complete absence of any malignant cell was considered as complete pathologic response (PCR). The last assessment of all the patients was done on April 2016. Results: Mean age was 46. Total 41(58.57%)patients were ERþ&PRþ,11Pts (15%) were triple negative . According to histopathology 32 Patients were well differentiated(Gr1&Gr-2)and rest 38 patients(54.28%) were poorly differentiated. In these 70 patients 32 patients had no residual malignancy anywhere indicating that in this series around 45.71% had complete pathological response (PCR). Conclusions: Pathological response to NACT is high in our population. The response is independent of age, grade& hormone status of tumor.This high rate could be due to the small deviations of our treatment schedule but perhaps more due to the biologically differenttumor behavior of this ethnically different group patients. A larger study may throw light on this issue. Legal entity responsible for the study: Mostafa Aziz Sumon Funding: N/A Disclosure: All authors have declared no conflicts of interest. 104P Pathologic tumor response & long term outcome with neoadjuvant trastuzumab in Her-2 positive breast cancer S. Zeeshan, S.M. Khan, N. Khan Surgery, The Aga Khan University Hospital, Karachi, Pakistan Background: HER2 receptor regulates cell growth, survival & differentiation. It is over expressed in 20% to 30% of all breast cancers & is associated with poor prognosis with a shorter time to relapse & lower overall survival rate. Trastuzumab is a HER2-directed humanized monoclonal antibody which is given in combination with chemotherapy to patients who have HER2-positive breast cancer. It significantly improves response rates, time to progression & overall survival in HER2-positive breast cancer compared with chemotherapy alone. Its use in the neoadjuvant setting significantly increases pathologic complete response (pCR) rates to as high as 65% which correlates with better survival Methods: Breast cancer database was retrospectively reviewed to determine the pathologic response to neoadjuvant trastuzumab in HER2-positive breast cancer & correlate long-term outcomes and to compare the incidence of pCR in HER2-positive & HER2-negative patients receiving neoadjuvant chemotherapy only with their outcomes Results: Out of 3766 patients, 448 fulfilled the selection criteria. 13.8% of HER2-positive patients received Neoadjuvant chemotherapy (NAC) along with neoadjuvant trastuzumab, 14% of HER2-positives received NAC without trastuzumab. A parallel group of HER2-negative patients who received NAC was also included. Incidence of Volume 27 | Supplement 9 | December 2016 pCR was highest in patients who received targeted therapy (54.8%) & showed favorable disease free survival. Absence of targeted therapy in patients who were HER2-positive yielded lower incidence of pCR (23.9%) similar to HER2-negatives receiving NAC only. In the long-term outcome, tumors with pCR showed better DFS (94.9%) with lower recurrence (5.1%) as compared to tumors with no pCR. Recurrence was found to be highest in HER2-positives who did not receive trastuzumab at all (20% vs 4.7% in neoadjuvant trastuzumab group) Conclusions: In HER 2-positive breast cancer, neoadjuvant Trastuzumab significantly increases pCR rate with a better long-term outcome Absence of targeted therapy in HER2-positive tumors yields lower incidence of pCR In the long-term outcome, HER2positive patients who do not receive trastuzumab show a higher incidence of recurrence Legal entity responsible for the study: The Aga Khan University Funding: The Aga Khan University Disclosure: All authors have declared no conflicts of interest. 105P Retrospective analysis of complete pathological response in locally advanced HER2 positive breast cancer patients treated with neoadjuvant chemotherapy associated to trastuzumab at Brazilian National Cancer Institute A.S. Nunes, A. Goncalves, J. Ominelli, S. Costa ^ncer (INCA), Rio de Janeiro, Brazil HC III, Instituto Nacional de Ca Background: Pathological complete response (pCR) is associated with better outcomes such Disease Free Survival (DFS) and Overall survival (OS) in high risk patients, like triple negative breast cancer and human epidermal growth factor receptor 2 (HER2) positive breast cancer. In neoadjuvant setting, randomized trials have shown that pCR would be improved with addition of Trastuzumab to chemotherapy. Methods: We analyzed 187 patients with primary HER2 positive breast cancers given neoadjuvant chemotherapy with trastuzumab. About 161 (86,2%) were clinical stage III. They underwent neoadjuvant treatment followed by surgery between January 1, 2008, and December 31, 2013. Hormone therapy and Radiotherapy were added to adjuvant treatment when needed. Data were collected from our internal database and patients’ files. The primary endpoint was pCR rate (ypT0/is, ypN0). Secondary endpoints included DFS, OS and cardiac toxicity. Tumor subtypes and chemotherapy protocol (FAC-TH or AC-TH) were registered. The safety profile was evaluated during the entire year of trastuzumab administration. Results: The pCR rate was seen in 50 (26,7%) patients, corroborating international data. The median time of follow up was 39,7 months (IC 95% 35,7-43,6), but not enough to determine DFS and OS. 19 (18,1%) and 27(39,7%) patients treated with FAC-TH and AC-TH, respectively, had pCR with statistic significance (p¼ .002). Among 112 patients with positive hormone receptor (ER and/or PR) and 75 with HER 2 enriched (ER and PR negative), 28 (25%) and 22 (29,3%) had pCR, respectively, without statistic significance (p¼ .512). 35 (18,7%) patients had reduction of LVEF superior to 10% and 22 (11,8%) patients needed to discontinue trastuzumab. Conclusions: Neoadjuvant chemotherapy associated to trastuzumab improved the pCR rate even in locally advanced tumors. There was no significant difference in pCR between HR positive and negative groups. The chemotherapy protocols influenced the primary endpoint with an acceptable safety profile. Legal entity responsible for the study: Brazilian National Cancer Institute Funding: Brazilian National Cancer Institute Disclosure: All authors have declared no conflicts of interest. 106P Sentinel lymph node after neoadjuvant chemotherapy in patients with locally advanced breast cancer A. Chikh Youssef Gynecologic Oncology, Obstetrics Gynecology University Hospital, Damascus, Syria Background: Sentinel lymph node provides reliable node staging information for clinically node negative and chemo naive breast cancer patients while its role after neoadjuvant chemotherapy remains unclear due to high false negative rate reported in previous studies. Methods: From may 2015 to may 2016 33 patients were enrolled all of them received neoadjuvant chemotherapyfor locally advanced breast cancer patients underwent sentinel lymph node using blue dye and axillary lymph node dissection. Results: 33 patients underwent sentinel lymph node and axillary lymph node dissection following neoadjuvant chemotherapy no cancer was found in the axillary lymph nodes of 8 patients PCR 24,3% in 5 patients cancer was not identified in the sentinel lymph node but was found in lymph nodes obtained from axillary lymph node dissection (false negative rate 15,2%). doi:10.1093/annonc/mdw576 | ix31 abstracts Conclusions: Among women receiving neoadjuvant chemotherapy the false negative rate was not 10% or less so we can’t support the sentinel lymph node as alternative to axillary lymph node dissection another change in approach and patients selection may improve sentinel lymph node sensitivity . Legal entity responsible for the study: Obstetrics Gynecology University Hospital Funding: Obstetrics Gynecology University Hospital Disclosure: All authors have declared no conflicts of interest. Annals of Oncology marker for increased vulnerability to chemotherapy-induced memory impairment in TNBC survivors. Legal entity responsible for the study: N/A Funding: National Natural Science Foundation of China Disclosure: All authors have declared no conflicts of interest. 109P 107P Assessment of correlation between polymorphism of leptin gene promoter (LEP G2548) with its serum levels in patients and controls Z. Tahmasebi Fard Biology, Islamic Azad University, Tehran, Iran Background: The hormone leptin is produced by fat cells and to help the regulation of energy balance by inhibiting hunger. Fat reserves are a set of actions of leptin. Obesity is associated with increased mortality in a range of cancers, including hepatocellular carcinoma, colon cancer, breast cancer, ovarian cancer and prostate cancer. This communication mechanism is not known so far. In this study, were studied the relationship between nucleotide changes LEP Rs 7799039 (-G2548A) in the leptin gene and concentration of leptin in serum. Methods: For this study, were selected 158 patients with breast cancer and 158 healthy controls. Then, serum and DNA of samples was extracted from blood. All samples were amplified and partially of PCR products were digested by Hha I restriction enzymes until to determine the genotype of individuals. In addition, serum leptin concentrations in both groups were assessed by ELISA technique. At the end of the study were used SPSS 23 software for analysis of data. Results: Between the two groups was seen statistically significant relationship for age (p ¼ 0.001); body mass index (p ¼ 0.000); smoking (p ¼ 0.026) and serum leptin concentrations (p ¼ 0.001). The risk of breast cancer in patients with mutant genotypes AA was detected 1.68 times higher than those without this genotype (p value¼ 0.036, OR: 1.686, CI95%: 1.033-2.753). But GG genotype showed a protective effect against cancer (p value¼ 0.005, OR: 0.523, CI95%: 0.333-0.821). Also for heterozygous genotype was seen 1,508 times higher than other people’s (p value¼ 0.202, OR: 1.508, CI95%: 0.800-2.841). But none of the genotypes was not associated with serum leptin concentration. Conclusions: Mutant allele A of LEP G2548 polymorphism was associated with breast cancer risk. But this polymorphism did not show the statistical relationship with serum leptin concentrations. Legal entity responsible for the study: N/A Funding: Islamic Azad University Disclosure: All authors have declared no conflicts of interest. 108P COMT, APOE, and BDNF gene polymorphisms modulate chemotherapy-induced cognitive impairment in breast cancer survivors L.G. Reddy1, S. P.s1, K. Kumarswamy1, K.G. Kallur1, R. Ragavendra2, A.B.S. Kumar1 1 Radiation Oncology, HCG Bangalore Institute of Oncology Speciality Centre, Bangalore, India, 2Statistics, HCG Bangalore Institute of Oncology Speciality Centre, Bangalore, India Background: Irrespective of molecular subtypes neoadjuvant chemotherapy has been a preferred initial component of multi-modality treatment for locally advanced breast cancer patients. Over the last decade very few studies have been conducted to study the value of 18F-FDG PET-CT (Positive emission tomography and computed tomography) in response evaluation post neo adjuvant chemotherapy and linking it to molecular subtypes. In this study we tried to evaluate the predictive capacity of PET-CT for histopathological response post neo adjuvant therapy and linking it with molecular subtypes of breast cancer based on ER (Estrogen receptor), PR(Progesterone receptor), HER-2 (Human Epidermal Growth factor-2) and KI-67 status. Methods: 30 patients of stage II&III breast cancer patients who received dose dense doxorubicin/cyclophospomide (2weeklyx4 cycles) and paclitaxel (weeklyx 12 cycles) based neoadjuvant chemotherapy were enrolled for the prospective study from 2015 to 2016.FDG PET/CTs were acquired at diagnosis & after completion of chemotherapy prior to surgical intervention for evaluation of metabolic response (Standard uptake values- SUVs) and relating the same with molecular subtypes (Luminal A{ERþ, PRþ, KI-67-< or equal to 14%), Luminal B {ERþ, PRþ, KI-67->14%}, Luminal Her2Neu{ERþ, PRþ, Her-2 neuþ}, Her-2 neu Enriched{ER-, PR-, Her-2neuþ}, Basal{ER-, PR-, Her-2 neu} using chi-square test for propotions. Results: The mean age of the sample was 50.9 years. Overall complete response was seen in 51.6% and partial response was seen in 48.4% following neoadjuvant chemotherapy when co-related with the SUVs of the PET-CTs and histopathological reports postsurgery. Complete response was maximum in basal types (75%), followed by luminal B (55.6%), Luminal A (50%), Her 2 enriched(40%) and Luminal Her2 (28.6%) though the distribution of proportions was not significant. Conclusions: Results suggest that PET-CT forms an important component of evaluation prior to neoadjuvant chemotherapy to assess responses. Molecular subtypes of breast cancer differ in their responses to dose dense neoadjuvant chemotherapy. Legal entity responsible for the study: Healthcare Global Enterprises Funding: Healthcare Global Enterprises Ltd Disclosure: All authors have declared no conflicts of interest. 110P W. Li Department of Oncology, 2nd Hospital of Anhui Medical University, Hefei, China Background: The aim of this study was to investigate whether COMT, APOE and BDNF gene polymorphisms modulate chemotherapy-induced cognitive impairment (CICI) in breast cancer survivors. Methods: Eighty triple negative breast cancer (TNBC) and 165 non-triple negative breast cancer (NTNBC) matched for age and education were respectively administered with a battery of neuropsychological tests including memory questionnaires before and after chemotherapy. Six single-nucleotide polymorphisms (SNPs) within COMT (rs165599, rs4680, rs737865), APOE(rs429358, rs7412) and BDNF (rs6265) gene were evaluated. Results: Compared with the memory scores of breast cancer patients before chemotherapy, the score of breast cancer patients after chemotherapy was poorer, exhibited significant difference (t¼-5.317, z ¼ -3.372, respectively, p < 0.01). Further, compared with NTNBC patients, memory scores of TNBC were poorer, exhibited statistical significance difference after chemotherapy (t¼-5.997, z¼-5.284, respectively, p < 0.01). Genotype of the COMT rs165599 had significantly lower odds of developing cognitive decline than the patients with the G/G genotype. Neither APOE (rs429358, rs7412) or BDNF (rs6265) had no statistically significant differences between the two groups. Further, linear regression revealed that the dominant model of COMT rs165599 (beta¼-1.441, 95%CI¼-2.781-0.101) was found to be significantly associated with retrospective memory (RM) questionnaires. Conclusions: The results suggests CICI in TNBC survivors were poorer than NTNBC after chemotherapy, and the COMT rs165599 polymorphism may be a potential genetic ix32 | abstracts Impact of FDG PET-CT in response evaluation of different molecular subtypes of locally advanced breast cancers post dose dense neoadjuvant chemotherapy Predictive value of tumor response rate for axillary response of neoadjuvant chemotherapy in patients with clinically nodepositive breast cancer H.S. Kim, Y.H. Eom, T.K. Yoo, B.J. Song, B.J. Chae Surgery, Seoul St. Mary’s Hospital, of the Catholic University, Seoul, Republic of Korea Background: Neoadjuvant chemotherapy (NAC) is the standard treatment for patients with clinically node-positive breast cancer. An axillary pathologic complete response (pCR) is associated with excellent prognosis, and patients who achieve axillary pCR can be spared axillary lymph node dissection (ALND). The aim of this study was to assess the factors that predicted axillary pCR and evaluated a model predicting of axillary pCR in our patient population. Methods: We retrospectively identified 201 patients with clinically node-positive breast cancer who were treated with NAC and underwent ALND between 2010 and 2015 at Seoul St. Mary’s Hospital, Catholic University of Korea. We analyzed the Baseline patient and tumor characteristics, clinical tumor response rate, pathologic nodal responses. The tumor response rate was calculated by the rate of tumor and nodal size reduction by the Response Evaluation Criteria in Solid Tumors ver. 1.1. The overall prediction of the model including tumor response rate was assessed by the discriminative performance by receiver operating characteristic (ROC) curve analysis. Results: Axillary pCR was achieved for 68 patients (33.8%) who underwent ALND after NAC. Patients presenting with high nuclear grade [grade 3 vs. 1 and 2, odds ratio (OR) 2.59], higher Ki-67 value [14% vs.h14%, odds ratio (OR) 1.97] and tumor response rate [47.1% vs. < 47.1%, odds ratio (OR) 3.86] were more likely to achieve nodal pCR. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology In multivariate analysis, tumor response rate was the only independent predictor of a pCR (p ¼ 0.0006). The analysis of tumor response rate values revealed that 47.1% was a reasonable cutoff value for predicting the response to nodal pCR. The discrimination of the model using tumor response rate status versus excluding tumor response rate status [area under the curve (AUC) 67.5%, 95% CI, 0.59-0.76] was significantly improved using tumor response rate status [area under the curve (AUC) 74.9%, 95% CI, 0.68-0.82, P ¼ 0.01]. Conclusions: Tumor response rate can predict axillary pCR in node-positive patients receiving NAC. This prediction model including tumor response rate shows reasonable accuracy for predicting axillary pCR and may have utility for informing treatment decisions. Legal entity responsible for the study: Seoul St. Mary’s Hospital Funding: Seoul St. Mary’s Hospital Disclosure: All authors have declared no conflicts of interest. 111P BMI effect prognostic features of breast cancer treatments M.I. Hojouj, I. Bondarenko Oncology and medical radiology, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine Background: The (BMI) on the prognosis of metastatic breast cancer (MBC) has not been explored so far. Aim of this retrospective study is to evaluate the relation between patients’ Breast cancer (BC) to BMI and the prognosis of treatment. Methods: The study included 143 patients with MBC between the ages of 30 and 76 (57,6 6 1) yrs of age who were treated according to our clinic from 2006-2014. The main condition for selection was the treatment of MBC at the time of analysis. All patients were evaluated according to the following data: stage of the disease, age and BMI at the time of diagnosis, the size, histological type and degree of differentiation of the tumor and the presence of regional lymph nodes (RLN) metastases.Tumor size was evaluated after measuring its maximal diameter and distributed in accordance with the International TNM-classification . The absence of menstruation in patients over 1 year up to the moment of diagnosis was regarded as menopause. T. BMI is calculated by the formula:I ¼ m h2, where m - body weight (kg) h -those with a BMI <25 kg/m2 - normal or underweight; from 25 to 29.9 kg/m2 - overweight; 30 kg/m2 - obese. The material for the histopathological study was obtained during surgery. Results: 1. In this retrospective study, among 108 patients with breast cancer, 44% were identified with excess body weight, and 31% - of various obesity degree. 25% Patients with normal BMI. 2. Patients with a BMI <25 kg/m2 34% were significantly more diagnosed with BC triple negative At the time of primary diagnosis marked the early stages of the disease. 3. BMI> 30 kg/m2, 11% more often associated with metastatic RLN, which is anindirect sign of a higher metastatic potentials. 4. Patients with normal BMI had significantly longer overall survival (OS) and disease-free survival (DFS) than patients with intermediate or obese BMI in pairwise comparisons adjusted for other factors, But this fact is preliminary and requires further study. Conclusions: This retrospective investigation our patient I–VI demonstrates that BMI is an independent prognostic factor in patients with BC. We have supporting evidence that obese BMI represents a poor risk feature for outcome, especially in pre-/ perimenopausal patients. Clinical trial indentification: October 2015, UAE Legal entity responsible for the study: Hojouj Funding: Hojouj Disclosure: All authors have declared no conflicts of interest. 112P Impact of surgery on psychological distress in women with breast cancer N.A. Jadoon1, F.U. Sulehri2, M. Hussain2, A. Ijaz3 Medicine, Ittefaq Hospital, Lahore, Pakistan, 2Medicine, Nishtar Medical College and Hospital (NMC) Clinical Oncology, Multan, Pakistan, 3 Gastroenterology, Hull Royal Infirmary, Kingston Upon Hull, UK 1 Background: The various surgical procedures for early-stage breast cancer are equivalent in terms of survival. In this context other factors, such as the effect of intervention on psychological health, psychosocial adjustment and quality of life assume great importance. The objective of this study was to estimate the prevalence of psychological distress in breast cancer patients who had undergone surgery and compare them with those who had not received surgical intervention. Volume 27 | Supplement 9 | December 2016 Methods: The study was carried out in outpatient department of Multan Institute of Medicine and Radiotherapy, Multan. The study group comprised of 90 breast cancer patients who were divided into 2 groups on basis surgery for breast cancer. Aga Khan University Anxiety & Depression Scale (AKUADS) was used to assess the prevalence of psychological distress. Results: Out of 90 patients who were interviewed, 55 were found to have clinically significant levels of anxiety and depression symptoms as measured by AKUADS. Women who had undergone surgery were found to be significantly less depressed than those who had not received such intervention (51.11% vs. 71.11% OR ¼ 2.35, 95% CI ¼ 1.31-4.22, p < 0.05). Although mastectomy patients were more depressed than those who had breast conserving surgery but the difference did not reach significant proportions (OR ¼ 1.33, 95% CI ¼ 0.76-2.32, p > 0.05). Similarly there was no difference between patients who were recently treated and those who received treatment long ago in terms of psychological distress (OR ¼ 1.23, 95% CI ¼ 0.70-2.15, p > 0.05). An intriguing finding was lesser prevalence of depression in women whose surgeons allowed them chose the type of surgery (OR ¼ 0.39, 95% CI ¼ 0.22-0.69, p < 0.05). The factors found to be affecting psychological distress in surgery patients group were living in rural area (OR ¼ 1.99, 95% CI ¼ 0.96-3.06), having low income (OR ¼ 2.66, 95% CI ¼ 1.50-4.70), and being physically inactive (OR ¼ 2.47, 95% CI ¼ 1.39-4.38). Conclusions: Findings from this study show that breast cancer patients have less psychological distress following surgery. The results show the need of psychosocial interventions and patient centered solution for evidence based selection of optimal treatment. Legal entity responsible for the study: Nishtar Medical College Hospital Multan Funding: Nishtar Medical College Hospital Multan Disclosure: All authors have declared no conflicts of interest. 113P Chemotherapy administration safety standards for preventing medication errors and adverse drug reactions in patients with breast cancers A. Fani Pakdel1, M. Mousavi2, M.S. Roohani3, S. Elyasi3, M.M. Kooshyar4 Radiation Oncology, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran, 2Kian-health Darou company, Mashhad University of Medical Sciences, Mashhad, Iran, 3Department of Clinical Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran, 4 Hematology and Oncology, Emam Reza Educational, Research and Treatment Center-Mashhad University of Medical Sciences, Mashhad, Iran 1 Background: The high toxicity and low therapeutic index of antineoplastic drugs make medication errors a notable problem which can culminate in excessive patient morbidity and cost. To boost the quality of care provided in medicine, it is essential to implement a system that reduces the number of chemotherapy errors. In the current study, the authors aimed to evaluate effect of implementation of standard form and detect medication error and adverse drug event (ADE) rates involving cytotoxic drugs used in breast cancer regimen in the outpatient chemotherapy setting. Methods: A cross sectional-interventional study was performed prospectively in two adult outpatient centers. To avoid errors, a standardized order sheet was established to document information regarding breast cancer chemotherapy. Effect of standard sheet on lessening errors in ordering and administration was evaluated. The epidemiology of Errors and Adverse drug events were reported. Results: Of 217 adult patient visits (164 visits in public hospital and 70 visits in private clinic) from 84 patients (64 in hospital and 20 in clinic) involving 385 medications, 41% were associated with a medication error. Of these errors, 5% occurring in private clinic compared with 95% of errors occurring in public hospital. A standardized approach helped to reduce errors in selection of regimen type However, physicians did not calculate doses on the basis of standard sheets so the most common error types were improper dose (38.2% of 89 cited error types). Effect of standard sheets in administering phase could not assess due to incomplete entering data by nurses. Sixty-two percent of errors originated in the prescribing phase of medication delivery, and 33% originated in the administering phase. ADE rate was 9.6% but no life-threatening adverse drug event was recorded. Conclusions: In the current study, authors found that standardized order sheets would be very beneficial and minimize medication errors if they are used accurately. Also this study provided important information about the rate and epidemiology of medication errors. Legal entity responsible for the study: N/A Funding: Mashhad University of Medical Sciences, Kian-health Darou company Disclosure: All authors have declared no conflicts of interest. doi:10.1093/annonc/mdw576 | ix33 abstracts 114P Annals of Oncology Comparison of conventional and hypo fractionation radiation schedule on pulmonary function test in carcinoma of the breast as an acute effect K. Ibrahim A1, H.B. Govardhan1, S. Pradhan2, P. Sridhar1, R. Jain3, S. Pallad1, T. Naveen1 1 Radiation Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India, 2 Radiation Medicine and Radiotherapy, Institute of Medical Sciences, Banaras Hindu University, IMS-BHU, Varanasi, India, 3Radiation Oncology, Pt.J.N.M.Medical College Raipur, Raipur, India Background: To evaluate the acute effect of different fractionation schedule (hypofractionation and convention fraction) of radiation therapy on lung in patient of carcinoma breast. Methods: This randomised prospective multicentric study was conducted with a 130 breast cancer patients who are all candidate for the adjuvant radiation therapy. Spirometry based PFT were done before radiation therapy as base line, at 1 month after RT and once in every 3 months.out of 130 patients, 70 were treated with hypofractionation (40Gy in 15#) and other 60 were treated with conventional fractionation schedule (50Gy in 25#) to chest wall and SCF(þ/-). All patients were treated with 3DCRT as per the departmental protocol of the institutes. The relative changes in the PFT parameters were correlated with irradiated lung dose by using dose volume histogram (DVH). Relevant statistical tests were used for analysis. Results: Conclusions: There will be more acute lung reaction (reflected on reduction on PT parameters) in conventional fractionation arm, patient with age more than 60 and ipsilateral lung volume of less than 950cc. Thus selection off patient still need to be caution on fractionation schedule. Further follow up to know weather the acute effect will reflect on late radiation effect. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 115P Male breast cancer - A single institution review N. Hariharan, T.S. Rao, C. C K Naidu, S. Patnaik, R.R. Iyer Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, India Background: Male breast cancer is a clinical rarity. In contrast to the detailed clinical data and randomised trials available on female breast cancer, only case series and retrospective audits are available for male breast cancer. We attempted to review our institution data from the past 5 years to add to the information available on this subject Methods: We reviewed the prospectively collected data between 2010 and 2015 for this study. All male patients with histologically proven breast cancer and available clinical data for analysis were included. Patients with gynaecomastia were excluded. We evaluated the clinical presentation, treatment given, histopathological differences and outcomes for this group of patients. Results: Of the 5020 breast cancer patients who underwent treatment in our institute between 2010 and 2015, we identififed 36 male patients. Of these, 21 patients met the inclusion criteria. Two thirds of them had central quadrant tumors while the remaining presented with tumors in the upper outer quadrant. 66% presented as locally advanced cancers (LABC) while the remaining were operable at presentation. None of the patients were denovo metastatic. Among the LABC, skin or muscle involvement occurred early, with half of them (n ¼ 7) being clinically T4. Matted nodes accounted for the remaining half of the LABC. Almost all of them were planned for upfront radical mastectomy except one who received anterior chemotherapy followed by surgery. The tumor histology was universally invasive ductal in nature. 28.5% of patients were node negative on final histopathology. The 3 year DFS for the whole group was 80.9%. Among the node positives, it was 73.3%. Conclusions: Male breast cancer forms less than 1% of all the breast cancers. They are universally invasive ductal in histology and tend to occur most frequently in the central quadrant with early skin and/or muscle involvement. 71.5% are node positive on final pathology. The 3 year DFS among node positive patients is 73.3%. This worse prognosis compared to female breast cancer could be due to the early involvement of skin/muscle or lymph nodes. Larger data series is necessary to throw more light on this rare entity. Legal entity responsible for the study: Basavatarakam Indo American Cancer Hospital and Research Institute Funding: Basavatarakam Indo American Cancer Hospital and Research Institute Disclosure: All authors have declared no conflicts of interest. Table: 114P Conventional Fractionation (60) PARAMETERS base line 1 months PFT Grade(No %) NORMAL MILD MODERATE SEVERE 44(73.3%) 37(61.6%) 12(20%) 13(21.6%) 4(6.6%) 1(1.6%) 7(11.6%) 3(5%) PFT values (mean) FVC FEV1 FEV MAX PARAMETERS Hemotologic toxicity GRADE 1 GRADE 2 GRADE 3 GRADE 4 SKIN GRADE 1 GRADE 2 GRADE 3 GRADE 4 2.28 1.97 3.51 ix34 | abstracts 2.08 1.90 3.47 3 months 28(46.6%) 14(23.3) 11(18.3%) 7(11.6%) 2.01 1.93 3.31 Hyporactionation schedule(70) base line 1 months 3 months 49(70%) 45(64.2%) 41(58.5%) 15(21.4%) 17(24.2%) 16(22.85%) 4(5.7%) 2(2.8%) 5(7.1%) 3(4.2%) 8(11.4%) 5(7.1%) 2.12 2.01 3.48 2.10 1.97 3.41 2.04 2.11 3.21 Conventional Fractionation (60) 20(33.3%)% 6(10%) 0 0 Hyporactionation schedule(70) 24(34.2%) 5(7.1%) 1(1.4%) 0 43(71.66%) 14(23.33%) 3(5%) 0 62(88.57%) 7(10%) 1(1.4%) 0 Volume 27 | Supplement 9 | December 2016 Annals of Oncology 27 (Supplement 9): ix35–ix41, 2016 doi:10.1093/annonc/mdw577 116O Palbociclib (PAL) plus letrozole (L) as first-line (1L) therapy (tx) in postmenopausal Asian women with estrogen receptor–positive (ER1)/human epidermal growth factor receptor 2–negative (HER2-) metastatic breast cancer (mBC) S-A. Im1, H. Mukai2, I.H. Park3, N. Masuda4, C. Shimizu5, S.B. Kim6, Y-H. Im7, S. Ohtani8, C.H. Bartlett9, D.R. Lu10, A. Mori11, E. Gauthier12, R.S. Finn13, M. Toi14 1 Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute Seoul National University College of Medicine, Seoul, Republic of Korea, 2Department of Breast and Medical Oncology, National Cancer Center Hospital East, Chiba, Japan, 3Center for Breast Cancer, National Cancer Center, Goyangsi, Republic of Korea, 4Department of Surgery, Breast Oncology, NHO Osaka National Hospital, Osaka, Japan, 5Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan, 6 Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 7Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 8Department of Breast Surgery, Hiroshima City Hospital, Hiroshima, Japan, 9Clinical Oncology, Pfizer Inc, New York, NY, USA, 10Oncology Clinical Statistics, Pfizer, La Jolla, CA, USA, 11Clinical Oncology, Pfizer S.r.l., Milan, Italy, 12 Clinical Oncology, Pfizer, La Jolla, CA, USA, 13Division of Hematology/ Oncology, David Geffen School of Medicine, Los Angeles, CA, USA, 14 Department of Breast Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan Background: Hormone tx (HT) is a mainstay 1L tx for ERþ mBC. PAL is a selective inhibitor of cyclin-dependent kinases (CDK) 4/6. In the PALOMA2 trial, PALþL as 1L mBC tx prolonged progression-free survival (PFS) v placebo (P)þL in patients (pts) with ERþ mBC. Median PFS (mPFS) (primary analysis) was 24.8 v 14.5 m, respectively (HR 0.58; P<.001) (Finn et al. ASCO 2016, #507). Here we assess efficacy and safety in Asian pts. Methods: 666 postmenopausal pts not given systemic tx for their ERþ/HER2– mBC were randomized 2:1 to PAL (125 mg/d oral [3 wk on, 1 wk off]) þ L (2.5 mg daily) or PþL. Primary endpoint was investigator-assessed PFS. Other key endpoints were response rate (RECIST 1.1) and safety. Tumor evaluations were every 12 wk. Safety and blood count assessments were at screening, biweekly during cycles 1–2, and on D1 of later cycles. Results: 95 Asian pts (65 PALþL; 30 PþL) enrolled. Median age was 60 (range, 43–88) yr. Baseline characteristics: distant relapse (78%), de novo disease (20%), or local/ locoregional recurrence (2%); prior (neo)adjuvant HT (66%), measurable disease (83%); 2 organs involved (73%); disease sites mostly involved bone (66%), lymph node (54%), and lung (39%); ECOG performance status (PS) 0–1/2 (94%/6%), for PS 2, 6/65 pts were from the PALþL arm. Investigator-assessed mPFS was 25.7 m (95% CI 19.2– NE) for PALþL v 13.9 m (7.4–22.0) for PþL (HR 0.48 [0.27–0.87], 1-sided P¼.007; independent radiologic assessment: HR 0.44 [0.23–0.84]; 1-sided P¼.005). All causality treatment-emergent adverse events (AEs) for all grades (Gr) occurred in 100%/97% of pts (PALþL/PþL). The most common AEs (all Gr; Gr 3–4) by treatment arms were for the clustered preferred terms of neutropenia (95%/13%; 89%/3%), infections (66%/50%; 5%/0%), and stomatitis (49%/20%; 0%/0%). Due to AEs, 57%/3% of pts had 1 dose level reduction of PAL/P and 8%/0% of pts discontinued PAL/P. Conclusions: In Asian pts with ERþ mBC, PALþL improved PFS v PþL. Treatment was mostly tolerable; neutropenia was generally manageable with dose modifications. PALþL should be considered as 1L HT for Asian women with mBC. Clinical trial indentification: NCT01740427 Legal entity responsible for the study: Pfizer, Inc Funding: Pfizer, Inc Disclosure: S-A. Im: Received research funding from AstraZeneca, advisory role for AstraZeneca, Roche, Novartis, and Hanmi. H. Mukai: honoraria from AstraZeneca, Eisai, Novartis Pharma and Taiho Pharmaceutical; research funding from Chugai Pharmaceutical, Nippon Kayaku, Novartis Pharma, Pfizer Japan, and Sanofi. N. Masuda: honoraria from Chugai, AstraZeneca, and Kyowa-Hakko Kirin; research funding from Chugai, Novartis, Pfizer, AstraZeneca, Lilly, MSD, and Kyowa-Kirin. C. Shimizu: research funding from Pfizer, Eli-Lily, Chugai, and the Ministry of Health, Labor and Welfare. C.H. Bartlett: Pfizer employee and a Pfizer stockholder. D.R. Lu, A. Mori, E. Gauthier: Employee of Pfizer and Pfizer stockholder. R.S. Finn: Consultant advisory role with Pfizer, Bayer, Novartis, Bristol Myers-Squibb; research funding from Pfizer. All other authors have declared no conflicts of interest. 117PD_PR Survival benefit of surgical removal for the primary tumor in stage IV breast cancer patients H.J. Kim, E. Kang, E. Kim, Y. Jang General Surgery, Seoul National University Bundang Hospital, Seoul, Republic of Korea Background: Several studies have suggested that primary tumor removal improved overall survival in stage IV breast cancer. However, survival benefit of local treatment still remains controversial. The purpose of this study is to determine whether surgical removal of the primary tumor provides survival benefits for stage IV breast cancer. Methods: We retrospectively reviewed the records of 157 patients who were diagnosed with stage IV breast cancer initially at Seoul National University Bundang Hospital between 2003 and 2015. The Kaplan Meier analysis was used for estimation of median survival. The log-rank test was used to compare differences according to patient and tumor characteristics. Multivariate cox regression analysis for survival was used for controlling potential confounding variables. Results: Of 157 stage IV breast cancer patients, 97 patents (62%) underwent surgical removal for primary tumor. The median survival was longer for patients who had better response of chemotherapy (70 vs. 47 months, p ¼ 0.023) and surgery (118 vs. 28 months, p < 0.001) than who did not. The median survival in patients who received radiotherapy was better than that in patients who did not (65 vs. 39 months, p ¼ 0.002). Patients with luminal A had a median survival of 118 months which was the longest compared to other subtypes (p ¼ 0.002). Multivariate Cox regression showed that surgery of the primary tumor and better response of chemotherapy were significantly independent predictors of survival (p < 0.001 and p ¼ 0.042). Conclusions: Our results showed that the primary tumor removal and good chemoresponse were associated with improvement in better survival. Therefore, surgical management for the primary tumor should be considered more actively in stage IV breast cancer patients. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 118P A retrospective comparison of eribulin and capecitabine in patients with HER2-negative metastatic breast cancer N. Tsushita1, T. Shimoi1, H.S. Okuma1, A. Kawachi1, A. Kitano1, T. Nishikawa1, A. Shimomura1, E. Noguchi1, M. Kodaira2, M. Yunokawa1, K. Yonemori1, C. Shimizu1, Y. Fujiwara1, K. Tamura1 1 Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan, 2 Medical Oncology, JIKOKAI Kodaira Hospital, Toda, Japan Background: Eribulin (ERI) is one of the standards of care in metastatic breast cancer (MBC) after anthracycline and taxane. In 301 trial, overall survival of ERI was comparable to that of capecitabine (CAP), though this trial failed to show the superiority of ERI over CAP. In the real world clinical practice, choice of ERI or CAP is a challenging problem. This study retrospectively compared ERI and CAP. Methods: The inclusion criteria were HER2-negative MBC patients treated with ERI and/or CAP between 2011 and 2015 after anthracycline and taxane. Overall response rate (ORR) was defined as the rate of CR and PR. Time to progression (TTP) was defined as a period from the initiation of ERI or CAP to PD or death. We analyzed ORR and TTP of ERI and CAP. We defined E group as the patients who received ERI only or who received ERI before CAP. We also defined C group as the patients who received CAP only or who received CAP before ERI. Median survival time (MST) of E group/C group was defined as the median time from ERI/CAP administration to death. We compared MST of E and C groups by treatment lines. Results: A total of 182 patients were included. The number of patients in E group/C group was 77/113. The median age of E group/C group was 57 [34-75]/59 [30-79] years. The proportion of triple negative breast cancer in E group/C group was 28.6/14.2%. The crossover rate of E group/C group was 39.0/75.7% (p < 0.001). ORR of ERI/CAP was 20.4/19.7% (p ¼ 1.00). TTP of ERI/CAP was 126/203 days (p < 0.0001). MST of E group/C groups were 422/1003 days (p < 0.0001). The number of patients of E group/C group in the 1st line, the 2nd line and the 3rd line was 15/27, 20/39 and 27/37, respectively. MST of E group/C group in the 1st line was 491/908 days (p ¼ 0.055), the 2nd line was 486/1003 days (p ¼ 0.0003), and the 3rd line was 442/1393 days (p ¼ 0.006). Conclusions: ORR of ERI was comparable to that of CAP, whereas TTP of ERI was shorter than CAP. MST was longer in C group than E group when compared in the same treatment lines. The inferiority of E group might reflect that fewer patients in E group were treated with CAP after failure of ERI. Reasons for the less crossover rate in E C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts Breast cancer, metastatic abstracts group should further be analyzed. Investigating specific subgroups for which one drug is more effective than the other will be the next step of our research. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 119P Efficacy and safety profile of eribulin mesylate in advanced breast cancer: Single-centre experience from India A. Sharma, D.C. Doval, K. Dutta, P. Goyal, R. Bajaj, M. Sharma, P. Jain Medical Oncology, Rajiv Gandhi Cancer Institute, Delhi, India Background: Patients with advanced breast cancer are usually resistant to anthracyclines and taxanes. Treatment failure is observed in majority of metastatic breast cancer patients and 5 year survival rate is only 27%. Treatment guidelines do not recommend any single agent or a combination regimen in particular sequence for advanced breast cancer. Eribulin mesylate a microtubule polymerization inhibitor is the first single agent chemotherapy with proven overall survival benefit and tolerable safety profile in advanced breast cancer patients. Methods: This is a retrospective analysis of 23 advanced breast cancer patients irrespective of hormone or HER2 receptor status. These patients were treated previously with anthracycline and/or taxanes and at least one chemotherapy for advanced disease. 1.4 mg/m2 eribulin mesylate was administered on day 1 and 8 of 21 days cycle until disease progression or occurrence of an unacceptable toxicity, or the patient not willing to continue the treatment. Results: Out of 23 patients analyzed, 11 patients responded to eribulin mesylate. Patients received average 4 cycles of eribulin mesylate. The objective response rate was 34.7% and clinical benefit rate was 47.8%. 8 patients had partial response. 4 patients even in 4th line of chemotherapy responded optimally to eribulin. Response rates were consistent in all patient subgroups. Neutropenia was the commonest reported adverse event (13%) followed by peripheral neuropathy (8.7%). Two patients reported grade 3 neutropenia and two patients reported grade 2/3 neuropathy. Disease progression was the most common reason for discontinuation of treatment with eribulin mesylate. Conclusions: Our single centre experience shows clinical outcomes similar to phase III clinical trials of eribulin mesylate and real world data mentioned in literature. Legal entity responsible for the study: Rajiv Gandhi Cancer Institute Funding: RGCI Disclosure: All authors have declared no conflicts of interest. 120P Survival outcomes of metastatic breast cancer who have been treated with bevacizumab and eribulin in the real world. - BEV 1 PTX followed by eribulin versus the reverse sequence K. Matsui1, M. Earashi2, T. Nagata3, A. Yoshikawa4, W. Fukushima5, Z. Nozaki6, Y. Tanada6, K. Oyama7, K. Shimada8, K. Kiyohara9, T. Shimizu10, K. Iwata11, T. Yoshida12, T. Ii13, K. Maeda1 1 Surgery, Toyama Prefectural Central Hospital, Toyama, Japan, 2Surgery, Yatsuo General Hospital, Toyama, Japan, 3Surgery and Science, Toyama University Hospital, Toyama, Japan, 4Surgery, Toyama City Hospital, Toyama, Japan, 5Surgery, Takaoka City Hospital, Takaoka, Japan, 6Surgery, Toyama Red Cross Hospital, Toyama, Japan, 7Surgery, Kouseiren Takaoka Hospital, Takaoka, Japan, 8Surgery, Imizu Municipal Hospital, Imizu, Japan, 9Surgery, Tonami Genaral Hospital, Tonami, Japan, 10Surgery, Saiseikai Toyama Hospital, Toyama, Japan, 11Surgery, Kurobe City Hospital, Kurobe, Japan, 12Surgery, Saiseikai Takaoka Hospital, Takaoka, Japan, 13Surgery, Kouseiren Namerikawa Hospital, Namerikawa, Japan Background: bevacizumab and eribulin represent novel agents for the treatment of HER2-negative metastatic breast cancer (MBC). However, there are difficult situations in making a clinical decision of when to choose which treatment option. Purpose A purpose of this study is to clarify a prognostic difference by the drug sequence in the real world. We used the database of Toyama Breast Cancer Research Group (TBCRG: multicenter study group) to evaluate whether sequential order of treatment affects survival benefit in patients who have been treated with both bevacizumab þ paclitaxel (BEVþPTX) and eribulin. Methods: All patients who started BEV þ PTX and eribulin treatment for MBC from Aug-2011 to Jun-2016 were selected in the database of TBCRG. Among 264 patients recorded in the TBCRG database, 180 patients had HER2-negative MBC. Of these, 55 patients were treated with both BEV þ PTX and eribulin sequentially regardless of treatment line. To evaluate the influence of sequential order, we compared the efficacy of eribulin followed by BEV þ PTX (arm E-B) to treatment with the reverse sequence (arm B-E). ix36 | abstracts Annals of Oncology Results: 28 patients were treated with E-B and 27 patients with the B-E sequence. The median progression free survival (PFS) was 9.6 and 14.1 months in arm E-B and arm BE, respectively (p ¼ 0.04). The median PFS with eribulin treatment was 3.7 and 4.1 months, respectively (p ¼ 0.57). On the other hand, there was a significant difference in the median PFS with BEV þ PTX treatment; 6.2 and 11.5 months, respectively (p ¼ 0.006). The respective median OS time was 17.7 and 26.1 months (p ¼ 0.11). Conclusions: These results suggest that when patients with HER2-negative MBC are treated with both BEV þ PTX and eribulin, patients with prior BEV þ PTX treatment is more likely to benefit than patients who are treated with prior eribulin treatment. Legal entity responsible for the study: TBCRG Funding: TBCRG Disclosure: All authors have declared no conflicts of interest. 121P Prognostic significance of the derived neutrophil lymphocyte ratio in metastatic breast cancer: A tertiary cancer care center analysis from India C.K. Das1, A. Gogia1, N.K. Shukla2, S. Deo2, S. Mathur3, D. Sharma4 Medical Oncology, All India Institute of Medical Sciences, New Delhi, India, 2 Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India, 3 Pathology, All India Institute of Medical Sciences, New Delhi, India, 4Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India 1 Background: Derived neutrophil-lymphocyte ratio (dNLR) is a marker of systemic inflammatory response produced by proinflammatory cytokine activity of tumour microenvironment. dNLR is a simple, easily reproducible biomarker can be used to stratify the prognostic subgroups and decide the management in metastatic breast cancer. There is sparsity of data regarding derived neutrophil ratio in India. We evaluated dNLR as a prognostic biomarker in metastatic breast cancer patients treated at a North Indian tertiary cancer care centre. Methods: We retrospectively reviewed the correlation between inflammatory biomarkers and clinical presentation and treatment outcome in 96 consecutively treated metastatic breast cancer patients between 2011-2014. Kaplan-Mere analysis done evaluate the impact on overall and progression-free survival. Results: Table: 121P Parameters Results Duration of presentation 9 months(1-120) Metastatic site bone: 59(60%), Lung:33(39%) liver: 22(22%) Receptor status ERþ/PRþHER2- 43(44%), ERþ/PRþHER2 þþþ:18(18%), ER-PR-HER2 þþþ: 15(15%), TNBC: 22(23%) Hemoglobin 11.2 gm%(6.5-14.3) TLC 6700/mm3 (3520-27200) ANC 4412/mm3 (1090-11900) Treatment Chemotherapy 79(81%), Surgery 43 (44%) Response rate ORR 53(54%), Complete remission 20(20%) Out of the 96 patients, the median age was 50 years (range 23-71 years. Forty-five (46%) patients had elevated dNLR.With a median follow-up of 19.4 months, the median Progression-free survival (PFS)and overall survival(OS) was 16.3 months and not reached respectively. 2-year estimated PFS and OS was38% and 75% respectively. Baseline high dNLR was associated with significantly low objective response rate (ORR)(p ¼ 0.003), inferior PFS (HR 3.5, 95%CI 2.01-6.07, p-value <0.005) and reduced OS (HR of 8.75, 95% CI ¼ 2.5- 29.9, P ¼ 0.001). On multivariate analysis, other significant factors were associated with inferior PFS were elevated absolute neutrophil count (HR 5.69, P 0.003, 95% CI1.7-18.3), response to chemotherapy (HR 0.22 P < 0.005, CI 0.11-0.45). Conclusions: In patients with metastatic breast cancer, inflammatory biomarker like elevated dNLR is strongly associated with low objective response rate, poor progressionfree and overall survival. In view of easy reproducibility, it can be incorporated in management decisions as a prognostic factor across subgroups. Legal entity responsible for the study: All India Institute of Medical Science, New Delhi Funding: All India Institute of Medical Science, New Delhi Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology 122P D.S. Heriyanto, I. Safitri, J. Purwani, N.A. Setyawan, I. Widodo Anatomic Pathology, Gadjah Mada University/Dr. Sardjito General Hospital, Yogyakarta, Indonesia Background: Prognosis of Breast Carcinoma (BC) depends on several important factors include lymph node status, histological grade, as well as HER2 status. Chemokine receptor CXCR 4 with its ligand CXCL 12, has important role in BC invasiveness. The role of CXCL 12 in BC metastasis and its correlation with prognostic factors is still unclear. Therefore, the study investigates the mRNA level of CXCR 4 and HER2 genes in primer tumor, as well as CXCL 12 gene in lymph node of patiens with and without metastasis and its correlation between each prognostic factor, is needed. Methods: This study involved 50 tissues, diagnosed as infiltrating ductal carcinoma of NST. Group was divided into no metastasis and metastasis. Total RNA was extracted from formalin fixed paraffin embadded. The CXCL 12, CXCR 4 and HER2 mRNA expression were analyzed using quantitative Real Time-PCR. Statistical analysis was performed using Mann-Whitney test and its correlation between each prognostic factor was analyzed using Spearman correlation test. Results: CXCL 12 expression was significantly higher in patients with metastasis compared to those without metastasis BC (p ¼ 0.007), however, CXCR 4 and HER2 expressions were not significantly difference in primary BC with and without lymph node metastasis. Statistic analysis revealed significant correlation between CXCL 12 expression and poorly grade tumor in metastasis (p ¼ 0.023; r ¼ 0.453), compare to those without metastasis, and CXCR 4 expression was significantly correlated with HER2 in both groups (p ¼ 0.025; and p ¼ 0.003). There was no significant correlation between CXCL 12 and CXCR 4 mRNA expression, as well as HER2 in both groups. However, CXCL 12 expression was significantly correlated with both groups (p ¼ 0.005) compare to those without metastasis. Conclusions: This study sugested that increase of CXCL 12 expression may have role as prognostic factor for lymph node metastasis and poorly histological grade of BC. The increased level of CXCR 4 mRNA is correlated with HER2 expression in primary tumor of BC. Legal entity responsible for the study: Didik Setyo Heriyanto Funding: Universitas Gadjah Mada Disclosure: All authors have declared no conflicts of interest. 123P 124P CXCL-12 is a potential marker to predict risk of lymph node metastasis in infiltrating duct carcinoma Stabilization of SDCBP oncoprotein and aiding breast cancer growth and metastasis: The role of A2BP1 A. Chatterjee, S. Jana, A. Bhattacharyya Department of Zoology, University of Calcutta, Kolkata, India Background: The main cause of breast cancer related death is metastasis and resistance to chemotherapy. Syndecan binding protein was reported to be responsible for cell migration, invasion and pseudopodia formation, all of which are links to tumor metastasis in different type of cancers including breast cancer .Our study aims to describe the stability of SDCBP mRNA during breast cancer. Methods: Gene expression status within the breast cancer (BC) samples and cell lines was analyzed by real time PCR and immunoblotting and also miR-103a expression was analyzed by real time PCR. Bioinformatic analysis of the SDCBP 3’ UTR for probable binding of RNA binding protein was done by RBPDB. Docking study and RNA EMSA was performed. Functional characterization of A2BP1 in BC growth and metastasis was performed by over and under expression of A2BP1 along with simultaneous inhibition of miR-103a. Results: SDCBP was found to be overexpressed in highly metastatic BC tissue. miR103a was found to be significantly overexpressed in highly metastatic cell lines and metastatic tissue samples, a targeting miRNA of SDCBP. So, to address this paradox of both miR-103a and its target gene SDCBP overexpression, a bioinformatic analysis revel that A2BP1 (RNA binding protein) might be interacting with 3’UTR SDCBP. RNA EMSA study confirmed the binding of A2BP1 within the 3’UTR of SDCBP. Next, overexpression and underexpression of A2BP1 was done to analyse its effect on BC progression and metastasis by modulating the expression of SDCBP. Finally, A2BP1 underexpression along with miR-103a inhibition study was done to confirm that A2BP1 stabilizes SDCBP and hence miR-103a cannot bind to its 3’ UTR and degrade it. Conclusions: In summary, our study defines the stabilization of the oncoprotein SDCBP mRNA by the RNA binding protein A2BP1, competing with miR-103a seeding region of the 3’UTR region of SDCBP. Legal entity responsible for the study: University of Calcutta, Kolkata and Department of Biotechnology, Government of India Funding: Department of Biotechnology, Government of India Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 Lack of HDAC1 and HDAC2 promote breast cancer aggressiveness N.S. Kamarulzaman1, H.D. Dewadas1, N.S. Yaacob2, N.F. Mokhtar1 Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Health Campus, Kota Bharu, Malaysia, 2Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Malaysia 1 Background: Dysregulation of histone deacetylases (HDACs) is one of the factors which affect transcriptional regulation of various genes involve in cancer progression. Owing to the discovery of HDAC inhibitors, studies on HDACs in pathological condition, particularly in various human cancers have increased in recent years. In breast cancer, HDAC1, HDAC2 and HDAC3 have been linked to cancer progression. However, the role of each HDAC in breast cancer with different metastatic potential remains unclear. This study aimed to investigate the role of HDACs in the aggressive and the less aggressive breast cancer cell types. Methods: Basal expression of HDAC1, HDAC2 and HDAC3 were measured using quantitative real-time RT-PCR and were compared between the aggressive and the less aggressive human breast cancer cell lines, MDA-MB-231 and MCF-7 cells, respectively. MCF-7 cells were treated with a HDAC inhibitor, Trichostatin A (TSA), at several concentrations (100-10 000 ng/ml) for 24h. Cell growth and migration assays were conducted to determine the effect of TSA on metastatic behaviour of MCF-7 cells. Results: In comparison to MCF-7 cells, the gene expression of HDAC1, HDAC2 and HDAC3 were expressed lower in MDA-MB-231 cells. Treatment with TSA on MCF-7 cells reduced the gene expression of HDAC1, HDAC2 but not HDAC3, in a dosedependent manner. Although the growth of MCF-7 cells was inhibited by TSA, the migration was enhanced. Conclusions: This study demonstrates the important role of HDAC1 and HDAC2 in the less aggressive breast cancer in suppressing metastasis, in which both molecules are lacking in the aggressive MDA-MB-231 cells. Additionally, these findings raise concern that the application of HDAC inhibitors as cancer therapy on cancer patients may establish metastasis. Legal entity responsible for the study: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Malaysia Funding: Ministry of Higher Education (MOHE), Malaysia Disclosure: All authors have declared no conflicts of interest. 125P Components of the PI3K/Akt pathway as prognostic factors in metastatic HER2-positive breast cancer treated with trastuzumab C. Veenstra1, S. Ellegård1, G. Pérez-Tenorio1, V. Fagerström1, J. Gårsjö1, K. Briedis1, M. Sundqvist2, A. Malmström1, S. Wingren3, O. Stål1 1 Clinical and Experimental Medicine and Department of Oncology, University Hospital Linköping, Linköping, Sweden, 2Surgery, County Hospital, Kalmar, Sweden, 3Medicine and Health, Universitetssjukhuset Orebro, Orebro, Sweden Background: HER2-positive breast cancer is an aggressive form of breast cancer, for which trastuzumab has been successfully used as treatment to improve patient outcome. Unfortunately, trastuzumab resistance often occurs, causing a major clinical challenge and to date no reliable biomarkers predicting resistance are available. We aimed to explore prognostic values of factors in the PI3K/Akt pathway. Methods: A clinical cohort of 47 patients with metastatic HER2-positive breast cancer was used. All patients received trastuzumab as part of their palliative treatment. Copy number variations and protein expressions of several components in the PI3K/Akt pathway were determined using droplet digital PCR and immunohistochemistry, respectively. Results: Patients with tumours showing high-grade ERBB2 amplification had a better overall survival (OS) and progression-free survival (PFS) compared with those with low-grade amplification. One through two copies of the gene encoding the tyrosine phosphatase PTPN2 resulted in a significantly improved OS and a trend towards better PFS. Similar results, albeit non-significant, were found with PTPN2 protein levels. Patients with cytoplasmic Met expression showed a trend towards better PFS than patients without this expression and high cytoplasmic S6K1 expression was related to a longer OS. Conclusions: The present results suggest that high-grade ERBB2 amplification and 0-2 copies of PTPN2 are positive prognostic factors in metastatic HER2-positive breast cancer treated with trastuzumab. This, together with the indicative findings on Met and S6K1, suggests that trastuzumab is more effective in highly proliferative tumours. Legal entity responsible for the study: Olle Stål Funding: Swedish Cancer Society, Medical Research Council of Southeast Sweden, Onkologiska klinikernas forskningsfond Linköping Disclosure: All authors have declared no conflicts of interest. doi:10.1093/annonc/mdw577 | ix37 abstracts 126P Assessment of EpCAM Intensity of Expression and Outcome in breast Carcinoma Neoadjuvant Chemotherapy Treated Patients A.M.R. Shalaby Oncologic Pathology, Kameda Medical Center, Kamogawa, Japan Background: Back ground: The wide use of Neoadjuvant chemotherapy nowadays became so wide to the degree that it is more or less established as a standard regimen in management of breast neoplasia, in spite of different outcome results. Expression of epithelial cell adhesion molecule (EpCAM) is deregulated in epithelial malignancies. It is found that it acts as signaling molecule with tumor-promoting functions in addition to its role in cell adhesion. Aim of Work: It is aimed to assess the expression intensity of malignant mammary cells of EpCAM and its relation to the patient out come and their response to neoadjuvant chemotherapy. Methods: 140 patients with breast carcinoma and undergone treatment with neoadjuvant chemotherapy were included in the study. Both Tru-cut tissue biopsy and radically-excised breast tissues; before and after neoadjuvant chemotherapy, were examined for intensity of staining by EpCAM. Results: High intensity of EpCAM expression pattern is found correlated with lymphovascular invasion status and higher nuclear grade (P ¼ 0.01 and 0.008, respectively), and was associated with poor outcome (P < 0.001). We also found that patients with high EpCAM expression before and after neoadjuvant chemotherapy showed worse pathological and clinical outcome (P ¼ 0.008 and <0.001, respectively) than the patients with high intensity before and low intensity after neoadjuvant chemotherapy. The overall survival rate of the first group is less than the second one (P ¼ 0.049). Conclusions: Strong EpCAM intensity in carcinoma of breast is correlated with bad response to neoadjuvant chemotherapy and subsequently with worse prognosis than in patients with negative or low staining intensity. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 127P Annals of Oncology Synergistic role of HIF-1a and Nav1.5 in potentiating breast cancer metastasis H.D. Dewadas1, N.S. Kamarulzaman1, N.S. Yaacob2, N.F. Mokhtar1 Institute For Research In Molecular Medicine (INFORMM), Universiti Sains Malaysia (Health Campus), Kubang Kerian, Malaysia, 2Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia (Health Campus), Kubang Kerian, Malaysia 1 Background: Hypoxia, a condition of low oxygen concentration especially in locally advanced solid tumors has emerged as a pivotal factor in tumor prognostic since it can initiate tumor progression and resistance to therapy. Under this condition, transcription factor HIF-1a is the major regulator that induces activation or repression of particular homeostatic regulatory genes leading to cancer cell survival and metastasis. Additionally, ion channels such as voltage-gated sodium channels (VGSCs), have been reported to be elevated in various metastatic cancer cells in the past two decades. Several recent studies captured VGSCs in having a mechanistic role in promoting invasion and migration. Specifically in aggressive breast cancer cells, an isoform of VGSCs, Nav1.5 exhibited an increased in expression. Since both HIF-1a and Nav1.5 are highly expressed in aggressive breast cancer cells, this study is designed to investigate the synergic contribution of HIF-1a and Nav1.5 which may provide a better strategy-plan to combat metastatic disease. Methods: Herein, HIF-1a was stabilized using cobalt chloride, CoCl2 (hypoxia mimicking agent) in the less aggressive breast cancer, MCF-7 cells which lack of HIF-1a and Nav1.5. mRNA of Nav1.5 and CA9 (a common target gene of HIF-1a) was analyzed by relative real-time PCR. Nuclear protein for HIF-1a was measured using Western blotting. Growth, lateral motility and transwell migration assays were conducted to investigate metastatic properties of the cells. Results: CoCl2 successfully increased HIF-1a nuclear protein and mRNA expression of CA9. This was followed by increased Nav1.5 mRNA expression. Although CoCl2 did not alter growth of MCF-7 cells, motility and migration were enhanced. Conclusions: In conclusion, increased mRNA of HIF-1a leads to upregulation of Nav1.5 expression. In combination, both molecules promote breast cancer cell aggressiveness though possible interaction between the two needs further studies. Legal entity responsible for the study: Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia Funding: Universiti Sains Malaysia Research University Grant, (1001/CIPPM/813060) Disclosure: All authors have declared no conflicts of interest. ix38 | abstracts 128P The alteration of p53-pathway gene expression in advanced breast cancer after neoadjuvant chemo- and hormone therapy S.I. Wanandi1, S. Dewi1, S. Pramana2, R. Karsono3 Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia, 2Biostatistics, Sekolah Tinggi Ilmu Statistik, Jakarta, Indonesia, 3Oncosurgery, Dharmais Hospital National Cancer Center, Jakarta, Indonesia 1 Background: Nowadays, neoadjuvant chemo- and hormone therapy has been widely used for locally advanced breast cancer patients to reduce tumor size. However, the effect of both neoadjuvant therapy (NAT) on metastatic breast cancer remains unknown, particularly in association with apoptotic-pathway. This study aimed to examine the expression alteration of p53-apoptotic pathways genes in advanced breast cancer patients after neoadjuvant chemo- and hormone therapy. Methods: We collected stage IIIb and IV breast cancer tissues from 46 patients before and after neoadjuvant chemo- (5-fluorouracil, anthracyclines, cyclophosphamides) and hormone (tamoxifen or aromatase inhibitor) therapy. Patients were treated for 6 months prior to tumor resection. The expression profile of p53-pathway genes was investigated using Next- Generation Sequencing and Targeted RNA expression p53 R , Illumina). The alteration of the p53-pathway panel comprising of 52 genes (TruSeqV gene expression after NAT was analyzed using dependent t-test and correlated with clinical characteristics and patients’ overall survival. Results: In this study, we found that the expression of 7 genes in p53 panel was significantly altered after NAT. Among these 7 genes, 3 apoptosis-inducing genes (ATM, CASP8 and CASP9) were overexpressed, whereas 1 anti-apoptosis genes BIRC5, as well as 2 proliferative genes (CDK1 and PCNA) were under-expressed. Surprisingly, the death-agonist BID gene was significantly underexpressed. No significant difference of these 7 gene expression profiles based on ER, PR and HER2 status, and NAT types. The ATM gene expression alteration was significantly different between stage IIIb and IV groups. Furthermore, we demonstrated that the alteration of PCNA gene expression was significantly correlated with the patients’ 3-years survival. Conclusions: Alteration of six p53-pathway gene expressions after NAT indicates the effectiveness of both chemo- and hormone therapy to suppress tumor proliferation and induce apoptosis in advanced breast cancer prior to mammosurgery. However, the overexpression of BID gene should be considered as an inducer of therapy resistance. Clinical trial indentification: This study has been approved by The Ethics Comittee of Faculty of Medicine, Universitas Indonesia. Legal entity responsible for the study: Faculty of Medicine, Universitas Indonesia Funding: Universitas Indonesia PT Pandu Biosains Disclosure: All authors have declared no conflicts of interest. 129P Inhibition of breast cancer cell explosion rate by irinotecan loaded zinc oxide nanoparticles through E2F3/Akt signaling circuits: A milestone in cancer gene therapy K. Vimala, K. Soundarapandian Zoology, Periyar University, Salem, India Background: The E2F3 transcription factor claims its role in controlling cell cycle progression. Accordingly, the present investigation has been designed to assess to what extent E2F3 would be overexpressed in breast cancer. Although chemotherapeutic drugs are widely applied for clinic tumor treatment, severe toxicity restricts their therapeutic efficacy. The present study was to emphasize that the synthesis of stable SiRNA (E2F3) conjugated irinotecan loaded Zinc Oxide Nanoparticles (SiRNAirinotecan-ZnONPs) and the elucidation of their mechanism of action in preventing the growth of breast tumors. Cell viability and expression of apoptotic markers (p58, Bax, and cytochrome c) were assessed and the level of E2F3 is increased in breast cancer and highlights the efficacy of siRNA targeted to E2F3. Methods: We used the green-bio method to synthesize SiRNA-irinotecan-ZnO nano complex for its use as a cancer-targeted drug delivery system to achieve enhanced cellular uptake and anticancer efficacy. To investigate the expression level of E2F3/Akt/ Mdm2/AR by RT-PCR and Western blotting analysis was carried out. Results: Here, we prepared siRNA conjugated irinotecan-ZnONPs against E2F3 significantly blocked the expression of the E2F3 in breast cancer and investigated its inherent anticancer mechanisms. We found SiRNA-irinotecan-ZnONPs inhibit growth of breast LNCaP cancer cells through activate Akt kinase and Mdm2 regulated degradation through proteasome pathway, dramatically inhibited tumor growth and significantly promote cell apoptosis. Conclusions: This in vitro and in vivo study demonstrates that E2F3 is a newly identified diagnostic and potential therapeutic target in breast cancer. Outcomes of this study affirm that SiRNA-irinotecan-ZnONPs for E2F3 facilitates the silencing of E2F3 overexpression and fights against breast cancer cells growth. These findings suggested that SiRNA-irinotecan-ZnONPs were deemed as a potential drug nanocarrier for cancer therapy and opens a new path for synergistic treating of cancer with higher efficacy and decreased side effects. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology Clinical trial indentification: In this study were approved by the Institutional Animal Ethical Committee of the Sankaralingam Bhuvaneshwai College of Pharmacy (622/PO/ c/02/CPCSEA/2014) in accordance with the policie established in the Guide to Care & Use of Experimental Animals prepared by the Committee. Legal entity responsible for the study: N/A Funding: PDFWM-UGC, New Delhi, India Disclosure: All authors have declared no conflicts of interest. 130P Locoregional treatment in de novo stage IV breast cancer: A retrospective study of Chinese population W. Wang1, X. Wang1, X. Wang1, J. Liu1, J. Gao1, P. Zhang2, D. Zhao3 Breast Surgical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China, 2Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China, 3 Abdominal Surgical Department, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China stagings were stage 1 (n ¼ 1), 2 (n ¼ 1), and 3 (n ¼ 3). The sensitivities, specificities, PPV and NPV for recurrence were as follows: on BSGI, 40%, 88.1%, 9.5% and 97.9%; on US, 100%, 92.5%, 29.4% and 100%, and on mammography, 33.3%, 100%, 100% and 98.6%, respectively. The diagnostic accuracies of BSGI, US and mammography were 86.7%, 92.8%, and 98.6%. Conclusions: The diagnostic accuracy of BSGI for detection of locoregional recurrence in breast cancer patients was 86.7%. BSGI was not superior to US or mammography in this regard. Therefore, BSGI should not be recommended for routine post-operative follow-up on breast cancer patients. Legal entity responsible for the study: Inje University Funding: N/A Disclosure: All authors have declared no conflicts of interest. 1 Background: The role of locoregional therapy of the primary in patients presenting with de novo stage IV breast cancer remains controversial. The aim of the present study was to evaluate the impact of locoregional resection and radiotherapy on survival of Chinese women with stage IV breast cancer. Methods: The retrospective study included Chinese patients with de novo stage IV breast cancer in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences between January 1st 2001 and November 30th 2015.Patients were identified as having local surgery if the date of breast-conserving surgery or mastectomy was within 1 year of initial breast cancer diagnosis date. All patients were treated with primary chemotherapy treatment. The target volume for locoregional radiotherapy was the chest wall and draining lymphatics and regimen delivered 50 Gy in 25 fractions. KaplanMeier curves were reported for overall survival (OS), and distant progression free survival (DPFS). Log-rank test was used to compare the difference in groups. Cox proportional models were fitted for multivariate analysis. Results: Of the 157 patients who presented with stage IV breast cancer, 66 (42.0%) underwent surgery, 52 (33.1%) patients received locoregional radiotherapy. Median age was 58.0 years (range 28 to 83 years). Median follow up time was 44.5 months (range 5 to 180 months). Median OS and DPFS were 36 months and 21 months. Patients in the surgery group had longer OS and DPFS than non-surgery group (5-y OS 93.3% vs 60.4%, P ¼ 0.002; 5-y DPFS 57.6% vs 26.4%, P < 0.001). DPFS was also significantly longer in patients who received radiotherapy (P ¼ 0.034). Multivariate analysis showed that surgical treatment was the only factor associated with OS (HR ¼ 0.41, CI ¼ 0.180.95, P ¼ 0.04), and response to systemic therapy (HR ¼ 0.24, CI ¼ 0.07-0.76, P ¼ 0.016), surgery (HR ¼ 0.43, CI ¼ 0.24-0.78, P ¼ 0.005) and PR status significantly influenced the DPFS (HR ¼ 2.97, CI ¼ 1.40-6.26, P ¼ 0.004). Conclusions: Locoregional surgical treatment and radiotherapy were associated with improved survival in Chinese patients with stage IV breast cancer. Response to systemic therapy and PR status may be impact factors for predicting prognosis. Legal entity responsible for the study: Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China Funding: Chinese Ministry of Science, National Program on Key Basic Research Project (973 Program) Disclosure: All authors have declared no conflicts of interest. 131P Breast-specific gamma imaging (BSGI) as follow-up after breast cancer surgery: Comparison with ultrasound and mammography S.Y. Yi1, J.Y. Park2 Hematology-Oncology, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea, 2Radiology, Myongji Hospital, Goyang, Republic of Korea 132P Quality of life and psychosocial needs of metastatic breast cancer patients T. Mehmood Radiation Oncology, Shaukat Khanum Memorial Cancer Hospital and Reserch Centre (SKM), Lahore, Pakistan Background: Review prior literature and patient survey reports related to metastatic breast cancer (MBC) patients’ quality of life (QoL) needs, and assess extent to which local organizations are meeting them. Methods: (1) Research findings of > 150 published, peer-reviewed research articles including quantitative and qualitative studies of MBC patients and their families, were summarized around the realities of living with MBC. (2) 13 surveys of 8,000 MBC patients were examined for common concerns. (3) Desk research analysis of leading nonprofits’ patient advocacy, research, education and support (n ¼ 16); and interviews with leadership about services for patients (n ¼ 16). Results: The extensive research base around MBC QoL issues was summarized into 6 categories: psychosocial distress; emotional support; information about the disease, its treatment, and resources; communication and decision making about care; relief of physical symptoms; and practical concerns. Sources of emotional support, individual and group psychotherapy, and counseling, as well as adequate information about the disease, its treatments, and methods to alleviate symptoms and side effects have been shown to be useful in helping patients cope with MBC. However, patients are typically not well informed in areas required for decision making about their care, and patient– clinician communication can be difficult. MBC symptoms and side effects of continuous treatment - fatigue, sleeping difficulties, and pain - and emotional distress interfere with daily life; supportive and palliative care is often insufficient. While the majority of the major local breast cancer advocate organizations focus on meeting the support needs of the breast cancer community, not enough attention is paid to the MBC patient population. Gaps in information include lack of detailed information on latest treatments, QoL, palliation, communication with health care providers, and advanced directives and end-of-life care. Conclusions: While QoL issues for MBC patients/caregivers are well understood, the resources and commitment to address these issues are still lacking. Targeted information and support services addressing QoL needs are as necessary to patients as medical treatments. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 134P Safety and efficacy of eribulin and trastuzumab in anti-HER2 therapy pretreated patients with HER2-positive metastatic breast cancer: A Japanese multicenter phase 2 study (SBP-04 study) 1 Background: To evaluate breast-specific gamma imaging (BSGI) for detection of locoregional recurrence after surgery in breast cancer patients and to compare it with ultrasound and mammography. Methods: Our study included 165 breast cancer patients who had undergone postoperative BSGI between August 2010 and December 2013. The imaging findings (BSGI, ultrasound [US] and mammography) were retrospectively reviewed for recurrence. The standard reference was the pathologic result and follow-up BSGI or US conducted within the past two years. The sensitivities, specificities, accuracies, negative predictive values (NPV), and positive predictive values (PPV) of BSGI, US and mammography were calculated. Results: Locoregional recurrence was confirmed in five patients. The recurrence sites were the contralateral breast (n ¼ 1), ipsilateral breast (n ¼ 1), ipsilateral axilla (n ¼ 1), supraclavicular area (n ¼ 1), and infraclavicular area (n ¼ 1). The previous pathologic Volume 27 | Supplement 9 | December 2016 T. Shien1, M. Ikeda2, S. Ohtani3, F. Hara4, M. Takahashi5, H. Tuji6, S. Yoshitomi6, K. Matsuoka7, Y. Ogasawara8, N. Taira1, H. Doihara1, S. Ohsumi5 1 Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan, 2 Breast and Thyroid Surgery, Fukuyama City Hospital, Fukuyama, Japan, 3 Breast Surgery, Hiroshima City Hospital, Hiroshima, Japan, 4Breast Oncology, Shikoku Cancer Center, Matsuyama, Japan, 5Breast Surgery, Shikoku Cancer Center, Matsuyama, Japan, 6Surgery, Okayama Red Cross Hospital, Okayama, Japan, 7Breast and Endocrine Surgery, Ehime Prefectual Central Hospital, Matsuyama, Japan, 8Breast and Endocrine Surgery, Kagawa Prefectual Central Hospital, Takamastu, Japan Background: The efficacy of eribulin for HER2 negative metastatic breast cancer (MBC) was confirmed by EMBRACE trial. However, there is no definitive Asian evidence about efficacy and safety of eribulin combined with trastuzumab (ET) for HER2 positive MBC. doi:10.1093/annonc/mdw577 | ix39 abstracts Methods: This study is a prospective multicenter phase II trial. HER2 positive MBC patients pretreated by chemotherapy with anti-HER2 drugs were enrolled. They received eribulin (1.4mg/m2) on day1 and 8 of each 21 days and trastuzumab by weekly (2mg/kg) or tri-weekly (6mg/kg) until progressive disease. Primary endpoint is objective response rate (ORR). Secondary endpoints are progression free survival (PFS), overall survival (OS), and safety. Results: 25 patients were enrolled. Median age was 62 (range 32-79). ER and PgR expression were positive in 15 (60%) and 9 (24%) patients approximately. Metastatic sites were 3 (12%) Bone/soft tissue and 22 (88%) visceral. 4 patients diagnosed brain metastases. The number of pretreated chemotherapy regimens was median 3 (range 27). 20 (80%) MBC patients had received taxane. Median cycle of ET was 5 (range 1-42). ORR and CRR were 36% and 48%. Best responses were CR: 1 (4%), PR: 8 (32%), SD: 7 (28%) and PD: 8 (36%). Long SD (> 6 months) was 3 (12%). Median PFS and OS were 5 and 30 months. Grade 3 adverse events were peripheral sensory neuropathy (12%), fatigue and appetite loss (4%), neutropenia (52%), leukopenia (36%) and ALT increased (4%). Conclusions: This study demonstrated that the combination therapy of eribulin and trastuzumab is effective and well-tolerated regimen for pretreated HER2 positive MBC patients, and appears to make disease stable for long time period. Clinical trial indentification: UMIN000009296 Legal entity responsible for the study: N/A Funding: Setouchi Breast Project Disclosure: All authors have declared no conflicts of interest. 135P A multicenter retrospective observation study about overall survival benefit of eribulin mesylate in comparison with taxane regimens for metastatic cancer patients Y. Kikuchi1, Y. Uchida2, H. Kanauchi3, T. Niwa1, K. Nishioka1, K. Tada1, M. Hashimoto4, H. Yasuda4, H. Kawabata5, Y. Seto1, T. Ogawa6 1 Breast and Endocrine Surgery, University of Tokyo, Tokyo, Japan, 2Breast Center, International University of Health and Welfare Mita Hospital, Tokyo, Japan, 3Breast Center, Showa General Hospital, Tokyo, Japan, 4Surgery, National Center for Global Health and Medicine, Tokyo, Japan, 5Breast and Endocrine Surgery, Toranomon Hospital, Tokyo, Japan, 6Breast Center, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan Background: Eribulin (Eri) has been reported to prolong overall survival (OS) in several studies with metastatic breast cancer (MBC) patients (pts). Recently, some reports have showed OS benefit in Eri comparison with taxane regimens for the early line MBC pts. Here we presented an analysis about the OS extension effect of Eri in a retrospective multicenter observation study for MBC pts. Methods: MBC pts who received eribulin or taxanes in the early line treatment from August 2011 to March 2014 in our institutes were analyzed. Taxane regimens included monotherapy of paclitaxel, docetaxel, nab-paclitaxel and the taxane combination with bevacituzumab. The efficacy including complete response (CR) and objective response rate (ORR) and adverse events were determined. Kaplan-Meier method was utilized to estimate median OS and survival post progression (SPP). And subgroup analysis of OS was by tumor subtypes and treatment-line. Results: A total 221 patients were analyzed included in this study and 101 pts received eribulin and 120 pts received taxanes. ORR was higher in eribulin than taxanes (49.5% vs 21.7%) and CR rate was 11% in eribulin and 0.4% in taxanes. The median OS and SPP were longer in eribulin than taxanes (OS: 22.3 months vs 13.6 months, SPP: 14.0 months vs 7.7 months). Subgroup analysis showed tendency of longer OS in MBC pts who had ER positive and visceral metastases, and who received in early line treatment. The major reason for discontinuing Eri treatment was due to increase of primary tumor size. Adverse events had been observed lower in Eri (1.0%) than in taxanes (16.0%). The study also found that the incidence of distant metastases at the time of PD was lower in patients receiving eribulin (11.3%) compared with those receiving taxanes (28.3%). Mean number of treatment regimens after the study therapy were 2.4 in eribulin and 1.5 in taxanes. Conclusions: From those analysis, the higher efficacy and acceptable safety profile of eribulin might contribute to prolonged survival. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. ix40 | abstracts Annals of Oncology 136TiP IMpassion130: Phase III trial comparing 1L atezolizumab with nab-paclitaxel versus placebo with nab-paclitaxel in treatment-naive patients with mTNBC L. Emens1, S. Adams2, S. Loi3, A. Schneeweiss4, H. Rugo5, E. Winer6, C. Barrios7, V. Dieras8, J. de la Haba-Rodriguez9, L. Gianni10, N. Kusuma11, S.Y. Chui12, P. Schmid13 1 Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 New York University School of Medicine, New York, NY, USA, 3Division of Cancer Medicine, Peter MacCallum Cancer Center, Melbourne, Australia, 4 Women’s Hospital, Heidelberg University Hospital, Heidelberg, Germany, 5 University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, USA, 6Dana-Farber Cancer Institute, Boston, MA, USA, 7 Department of Medicine, PUCRS School of Medicine, Porto Alegre, Brazil, 8 Medical Oncology, Institut Curie, Paris, France, 9Hospital Universitario Reina Sofıa, Cordoba, Spain, 10San Raffaele Scientific Institute, Milan, Italy, 11Roche Singapore Pte Ltd., Singapore, 12Genentech, Inc., South San Francisco, CA, USA, 13Barts Cancer Institute-Queen Mary University of London, London, UK Background: Chemotherapy remains the mainstay therapy for metastatic triplenegative breast cancer (mTNBC) but offers limited clinical benefit at the expense of significant toxicity. This underscores the need for new treatment options. Atezolizumab (atezo) is a mAb specific for PD-L1 that prevents PD-L1 binding to its receptors PD-1 and B7.1, thereby restoring tumor-specific T-cell immunity. TNBC is a rational target indication for atezo due to PD-L1 expression on tumor-infiltrating immune cells (IC), and a high mutation burden that may generate immunogenic neoantigens. Atezo monotherapy was well tolerated and produced durable responses in patients (pts) with mTNBC (Emens et al 2015). Promising activity observed in pts treated with atezo plus nab-paclitaxel (nab-pac) supports the hypothesis that the combination may represent an effective new treatment option for pts with mTNBC (Adams et al 2016). IMpassion130 (NCT02425891), a global Phase III randomized, multicenter, placebocontrolled clinical trial, is being conducted to evaluate the efficacy and safety of first-line (1L) atezo þ nab-pac compared with placebo þ nab-pac alone in treatment-naive pts with mTNBC. Trial design: Eligibility criteria include locally advanced or metastatic TNBC, no prior systemic treatment for advanced TNBC, measurable disease per RECIST v1.1, and ECOG PS 0-1. Exclusion criteria include untreated CNS metastases (asymptomatic treated CNS metastases permitted), prior exposure to immunotherapy and autoimmune disease. Pts are randomized 1:1 to receive atezo (840 mg q2w) or placebo on days 1 and 15, along with nab-pac (days 1, 8 and 15) in 28-day cycles. Stratification factors include presence of liver metastases, prior taxane therapy and PD-L1 expression < 1% vs 1% of IC (IC0 vs IC1/2/3 with VENTANA SP142 IHC assay). Co-primary endpoints of PFS and OS will be evaluated in the ITT population and in PD-L1–selected pts. Secondary endpoints include ORR and safety. Tumor biopsies obtained at baseline and disease progression will be assessed for biomarkers associated with responses to atezo and immune escape. Approximately 900 pts will be enrolled. Clinical trial indentification: NCT02425891 Legal entity responsible for the study: F. Hoffmann-La Roche Ltd Funding: F. Hoffmann-La Roche Ltd Disclosure: L. Emens: Honoraria/Consulting: Celgene, Amgen, Syndax, Vaccinex, Astrazeneca, Amgen, Research funding: Roche, Genentech, Astrazeneca, Serone, Maxcyte, Amplimmune. patent, royaties, Aduco Biotech-minor. Advisory Communitee FDA Cell Tissue and gene therapies. S. Adams: Genentech and Merck -Research funding. A. Schneeweiss: Honararia: Celgene, Roche; Research funding: Celgene. E. Winer: McKinsey honorarium for consulting Gerson Lehman honorarium for consulting Verastem honorarium for scientific advisory board. C. Barrios: Honararia/ Consulting: BI, GSK, Novartis, Pfizer, Roche, Eisai, Bioepis, Amgen; Research funding: Amgen, AZ, BI, GSK, Novartis, Pfizer, Roche, Eisai, Lilly, Sanofi, Celgene, Taiho, Mylan, Merrimack, Merck, Abbvie, Astellas, Daichi-Sankyo, Biomarin, BMS. V. Dieras: Consulting/advisory: Roche, Novartis, Pfizer, Elsai Speakers’ Bureau: Roche, Novartis, Pfizer Travel, accommodations, expenses, Roche, Novartis, Pfizer. J. de la HabaRodriguez: Honoraria- Roche Pharma AG Consulting or advisory role- Roche Pharma AG Research funding- yes- Roche Pharma AG. L. Gianni: Consulting & Travel: Roche, GSK, Pfizer, BI, Celgene, Tahio Pharma, Tiziana Pharma, Synthon, AZ, Genomic Health, Merck Sharp & Dohme, Synafflix. N. Kusuma: Employee of Roche Singapore Pte Ltd. S.Y. Chui: Genentech Employee, Research funding from Genentech/Roche. P. Schmid: Honoraria-AZ, Pfizer Consulting/advisory role - Roche/Genentech Research funding-Genentech, AZ, Astellas, OncoGenex. All other authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 Annals of Oncology 137TiP A phase III study of alpelisib and fulvestrant for hormone receptor-positive (HR1), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) progressing on or after aromatase inhibitor (AI) therapy (SOLAR-1) H. Iwata1, G. Rubovszky2, S. Loibl3, E. Ciruelos4, M. Campone5, D. Juric6, H. Rugo7, I. Mayer8, P.F. Conte9, B. Kaufman10, K. Inoue11, H. Tesch12, Y-S. Li13, I.D. Mingorance14, L. Ryvo15, H. Iwase16, A-S. Longin17, D. Mills18, C. Wilke18, F. André19 1 Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, 2Internal Medicine-Oncology Division “B” and Clinical Pharmacology, giai Intézet, Budapest, Hungary, 3Medicine and Research, Orszagos Onkolo German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg, Germany, 4 Breast Cancer Unit, University Hospital 12 De Octubre, Madrid, Spain, 5 Medical Oncology, ICO Institut de Cancerologie de l’Ouest René Gauducheau, St. Herblain, France, 6Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA, 7Department of Medicine (Hematology/Oncology), University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, USA, 81301 medical center dr suite 1710, Vanderbilt Ingram Cancer Center, Nashville, TN, USA, 9Division of Surgery, Oncology and Gastroenterology, Istituto Oncologico Veneto IRCCS, Padua, Italy, 10Division of Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel, 11Division of Breast Oncology, Saitama Cancer Center, Saitama, Japan, 12Onkologie Bethanien, Centrum für €matologie und Onkologie Bethanien, Frankfurt Am Main, Germany, Ha 13 Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, 14 Optional Medical Oncology Clinical Trials Unit, Hospital Infanta Cristina, Badajoz, Spain, 15Departments of Oncology, Tel Aviv Sourasky Medical Center(Ichilov), Tel Aviv, Israel, 16Breast and Endocrine Surgery, Kumamoto University, Kumamoto, Japan, 17Oncology Global Development, Novartis pharma S.A.S, Paris, France, 18Oncology Global Development, Novartis Pharma AG, Basel, Switzerland, 19Medical Oncology, Institut Gustave Roussy, Villejuif, France Background: The PI3K/AKT/mTOR pathway is often dysregulated in HRþ BC and is associated with resistance to endocrine therapy (ET). Alpelisib a PI3Ka-specific inhibitor and fulvestrant showed signs of antitumor activity in patients (pts) with ERþ, HER2– ABC (phase I), particularly in PIK3CA-altered tumors. Trial design: SOLAR-1 (NCT02437318) is a phase III, randomized, double-blind study in men and postmenopausal women with HRþ, HER2– ABC. Based on PIK3CA tumor Volume 27 | Supplement 9 | December 2016 abstracts status (mutant vs non-mutant) pts are assigned to 1 of 2 cohorts, and randomized 1:1 to oral alpelisib/placebo (300 mg once daily) and intramuscular fulvestrant (500 mg on Day 1 and 15 of Cycle 1; Day 1 of Cycles 2 [28-day cycles]) until disease progression or discontinuation. Randomization is stratified by presence of liver and/or lung metastases and prior CDK4/6 inhibitor therapy. Key inclusion criteria: recurrence or progression on or after AI therapy, 1 measurable lesion (RECIST v1.1) or predominantly lytic bone lesion, and ECOG performance status 1. Key exclusion criteria: symptomatic visceral disease or disease burden precluding ET, acute pancreatitis 1 year prior to screening or history of chronic pancreatitis, and prior therapy with fulvestrant, chemotherapy (except [neo] adjuvant), or PI3K/AKT/mTOR inhibitors. Progressionfree survival (PFS; RECIST v1.1; local assessment) and overall survival (OS), in the PIK3CA-mutant cohort are primary and key secondary end-points respectively. PFS (Blinded Independent Central Review; RECIST v1.1), PFS and OS in the PIK3CA nonmutant cohort, the association between PFS and baseline PIK3CA status in circulating tumor DNA, overall response rate, clinical benefit rate, pharmacokinetics and safety are other secondary endpoints. The primary endpoint will be analyzed by a stratified logrank test at one-sided 2% level of significance. Recruitment of the planned 560 pts is ongoing. Clinical trial indentification: NCT02437318 Legal entity responsible for the study: Novartis Pharmaceutical Corporation Funding: Novartis Pharmaceutical Corporation Disclosure: S. Loibl: My institution received research funding from Celgene, Amgen, Roche, Pfizer, Teva, Novartis. M. Campone: Novartis: Advisory board grant speaker bureau Menarini: Advisory board Astra Zeneca: Advisory board bureau Pfizer: Advisory board speaker bureau Roche: Advisory board. D. Juric: Advisory role to Novartis, EMD Serono, Eisai, BIND Therapeutics, Natera. Research funding received from Novartis. H. Rugo: Dr. Rugo does not receive funding personally. Funding is provided to her institution for the conduct of clinical trials sponsored by Novartis. I. Mayer: - Research funding and consulting fees from Novartis - Consulting fees from Genentech - Research funding from Clovis. P.F. Conte: Speaker and Advisory Boards for: novartis, roche, eli-lilly, celgene, astra-zeneca, obi Research Grants from: Novartis, Roche, Merck-serono. B. Kaufman: I participated in advisory board for Novartis. AstraZeneca Roche. H. Tesch: Employment or management position Established oncologist in the community oncology practice at the Bethanien Hospital Consulting activities: Novartis, Roche, Pfizer Fees: Novartis, Roche, Pfizer. D. Mills: Own stock in Novartis pharma AG. C. Wilke: Employee of Novartis, the sponsor of the study. F. André: Research support from Novartis. All other authors have declared no conflicts of interest. doi:10.1093/annonc/mdw577 | ix41 Annals of Oncology 27 (Supplement 9): ix42–ix45, 2016 doi:10.1093/annonc/mdw578 CNS tumours 138O Efficacy of a novel antibody-drug conjugate (ADC), ABT-414, with temozolomide (TMZ) in recurrent glioblastoma (rGBM) abstracts M. van den Bent1, A.B. Lassman2, H.K. Gan3, D.A. Reardon4, P. Kumthekar5, N. Butowski6, Z. Lwin7, T. Mikkelsen8, L.B. Nabors9, K.P. Papadopoulos10, M. Penas-Prado11, J. Simes12, H. Wheeler13, E. Gomez14, H-J. Lee14, L. RobertsRapp14, H. Xiong14, E. Bain14, K. Holen14, R. Merrell15 1 Neuro-Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands, 2 Department of Neurology & Herbert Irving Comprehensive Cancer Center, Columbia University, New York, IL, USA, 3Medical Oncology, Austin Health and Olivia Newton-John Cancer Research Institute; Department of Medicine, University of Melbourne; La Trobe University School of Cancer Medicine, Melbourne, Australia, 4Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, 5Department of Neurology, Northwestern University, Chicago, IL, USA, 6Department of Neurological Surgery, University of California, San Francisco, CA, USA, 7Department of Medical Oncology, University of Queensland School of Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Australia, 8Neurosurgery and Neuroscience Research, Henry Ford Health System, Detroit, MI, USA, 9Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA, 10Department of Clinical Research, South Texas Accelerated Research Therapeutics (START), Houston, TX, USA, 11Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 12NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia, 13Medical Oncology, Royal North Shore Hospital, Sydney, Australia, 14Global Pharmaceutical R&D, AbbVie Inc., North Chicago, IL, USA, 15Department of Neurology, NorthShore University Health System, Evanston, IL, USA Background: ABT-414 is a first-in-class ADC that selectively targets EGFR amplification (amp) to deliver a potent microtubule cytotoxin (monomethyl auristatin F) inside the tumor cells. Almost 50% of GBMs harbor EGFR amp. ABT414 monotherapy has shown preliminary efficacy in EGFR amp rGBM. Here we report safety and efficacy of ABT-414þTMZ in EGFR amp rGBM at the recommended phase 2 dose. Methods: Adults with rGBM harboring centrally-confirmed EGFR amp, adequate endorgan function, and KPS >70 were eligible. To isolate the effects of ABT-414 from TMZ, all patients (pt)s were TMZ refractory, defined as a recurrent/progressive disease <3 months from last TMZ. Pts received ABT414 1.25 mg/kg IV on days 1 and 15, and TMZ 150-200 mg/m2 on days 1-5 of 28-day cycles, until progression (RANO). Results: As of March 1, 2016, 32 pts were treated following 1 (n ¼ 21), 2 (n ¼ 8), or > 3 (n ¼ 1) prior therapies. The most common adverse events (AE)s (25% pts) were blurred vision (53%), photophobia (34%), headache (34%), fatigue (31%) and constipation (25%). Grade 3/4 AEs included (>1 pt) keratitis (16%), ataxia, decreased platelet count, hemiparesis and thrombocytopenia (6% each). Seizure was the most common serious AE, occurring in 13% pts. Neurologic AEs were generally attributed to the underlying tumor. No doselimiting toxicities were observed. Best radiographic responses in 31 pts with available imaging data were: 3 (10%) partial responses (PR), 18 (58%) stable disease (SD), and 10 (32%) progressive disease (PD). Pts with PD were allowed a repeat resection as clinically indicated. Four of them were found to have all or mainly treatment effect rather than active recurrence on histologic analysis; the progressionfree survival (PFS), response, and 6 month-PFS rates will be updated after clarifying their outcomes. Conclusions: In this TMZ refractory population, ABT-414 demonstrated 10% PR and 58% SD rates, although histology of tissue resected for presumed recurrence remains to be clarified, which may increase rate of disease control. No new safety events were observed and ocular toxicity was the most common AE. A global, randomized trial of ABT-414 alone or with TMZ, vs. TMZ or lomustine, is underway in rGBM (NCT02343406). Clinical trial indentification: NCT01800695 Legal entity responsible for the study: AbbVie Inc. Funding: AbbVie Inc. Disclosure: M. van den Bent: Received honoraria from Roche, Abbvie, Celldex, Novocure, Merck Ag, Cavion, Actelion, BMS, Blue Earth Diagnostics; received research funding from AbbVie and Roche. A.B. Lassman: Received personal compensation within the last 12 months from VBI Vaccines, Sapience Therapeutics, Cortice Biosciences, prIME Oncology, Abbvie, Genentech, Regeneron; Research support from Genentech, Amgen, AbbVie, Novartis, Karyopharm, Celldex, NW Biotherapeutics, Plexxicon, Pfizer, Agenus, Medimmune, Boehringer Ingelheim, Angiochem, Novocure, Stemline, E-Therapeutics, Millennium. H.K. Gan: Has an investigator-initiated study with AbbVie; received travel support and research funding from AbbVie; received honoraria from AbbVie, Pfizer and Merck Serono; affiliated with the Ludwig Institute for Cancer Research. D.A. Reardon: Received honoraria from and has a consulting or advisory role with Abbvie, Bristol Myers Squibb, Cavion, Celldex, Inovio, Merck, Novartis, Roche/Genentech, Amgen, Novocure, Oxigene, Regeneron and Stemline Therapeutics; is involved in speakers’ bureaus with Roche and Merck; received research funding from Incyte, Midatech and Celldex. P. Kumthekar: Received Honoraria for advisory role with AbbVie within the last 12 months. N. Butowski: Received honoraria from and has a consulting or advisory role with, Roche/Genentech, Medicenna, VBL Therapeutics, Omniox, Celldex; is involved in speakers’ bureaus with Roche and Merck; received research funding Insys. L.B. Nabors: Serves on a Scientific Advisory Board for Cavion. K.P. Papadopoulos: Received research funding from AbbVie, MedImmune, Daiichi Sankyo, GlaxoSmithKline, Onyx, Sanofi, Novartis. E. Gomez, H-J. Lee, L. Roberts-Rapp, H. Xiong, E. Bain, K. Holen: Employed by AbbVie and may own AbbVie stock. R. Merrell: Received honoraria for advisory role with Abbvie. All other authors have declared no conflicts of interest. 139O Systematic review and individual patient data analysis of uncommon GBM variants: An analysis of 196 cases S. Mallick, R. Benson, B. Venkatesulu, G.K. Rath Radiotherapy, All India Institute of Medical Sciences, Delhi, India Background: Different variant of GBM has been reported viz. Epithelioid GBM (GBME), Rhabdoid GBM (GBM-R), Small cell GBM (GBM-SC), Giant cell GBM (GBM-GC), GBM with neuro ectodermal differentiation (GBM-PNET) with unknown behavior. Methods: We conducted a systematic review and individual patient data analysis of rare GBM variants. We searched PubMed, google search, and Cochrane library for eligible studies till July 1st 2016 published in English language and collected data regarding age, sex, subtype, and treatment received, DFS, OS. STATA 12 software was used for all statistical analysis. Results: We retrieved data of 196 patients with rarer GBM subtypes. Among these GBM-GC is commonest (51%), followed by GBM-R (19%), GBM-PNET (13%), GBMSC (9%) and GBM-E (8%). Median age for these was 38, 40, 43.5, 69.5 and 18 years. Male: female ratio was 2:1 for GBM-E, 1:3 for GBM-SC. Maximal safe resection followed by adjuvant radiation was advocated for most of the patients. However, 6 GBM-PNET, 3 each of GBM-E, GBM-SC received Craniospinal radiation. Out of 76 patients, 50 received Temozolomide as adjuvant therapy. Median PFS and OS for the entire cohort were 8 and 16.5 months. In univariate analysis patient with a GTR had significantly better survival compared to those with a STR [23 vs. 13 months (p-0.01)]. Median OS for GBM PNET 32 months; GBM-GC 18.3 months; GBM-SC 11 months; GBM-R 12 months; and GBM-E 7.7 months (p ¼ 0.002). 31.3%, 37.8% patients with GBM-E, GBM-R had CSF dissemination. Conclusions: Overall cohort of rarer GBM variant has equivalent survival compared to GBM not otherwise specified. However, epithelioid and Rhabdoid GBM has worst survival and one third shows CSF dissemination. Legal entity responsible for the study: Supriya Mallick Funding: N/A Disclosure: All authors have declared no conflicts of interest. 140PD The role of leptin and its receptor in oligo-astrocytic neoplasms R.S. Vokuda1, S. Bh2, V.S. Madhugiri3, S. Kumar2 Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India, 2Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India, 3Neurosurgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India 1 Background: Leptin is the first member of the adipocytokines with a molecular weight of 16kDa. It functions in tandem with the leptin receptor, OB-R isoform which contains an intact intracellular domain that has the ability to activate the JAK/STAT pathway. It stimulates growth, migration, invasion of cancer cells in vitro and also potentiates angiogenesis justifying the malignant nature of leptin. Recently, leptin has been explored as an angiogenic entity, thus influencing several signalling systems involved in progression or development of tumors. Despite having advanced therapy regimens for the high grade tumors, they exhibit poor prognosis and low survival rates. Therefore search for novel therapy regimens has resulted in discovery of many potential C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts Annals of Oncology biomarkers & pharmaceutical targets. In this regard we analysed the potential role of leptin and its receptor in carcinogenesis of malignant gliomas. Methods: Fresh tissue samples of 60 cases of malignant astrocytoma/ Oligodendroglioma were collected after the excision of tumor with informed consent. Real time PCR and immunohistochemical (IHC) analysis were carried out to assess the expression of leptin and its receptor. Results: The present study demonstrates that the leptin and its receptor is overexpressed in malignant gliomas and could be involved in tumor progression. Of the total 60 cases, 57 cases (95%) and 55 cases (91.6%) showed amplification for leptin & OB-R respectively on real time PCR analysis. On IHC, the expression of these proteins were measured quantitatively and correlated with degree of malignancy which was also statistically significant (p < 0.05) with the grade of tumor. Conclusions: The real time PCR analysis for these genes has been done for the first time in Oligo-Astrocytic neoplasms using fresh tissue samples. It represents the first step towards understanding the molecular pathway of leptin and its receptor in these tumors. Leptin may be valued as a pharmaceutical target in malignant gliomas. Anti-leptin compounds could be developed as drugs in mono- or combined therapies for these tumors. Legal entity responsible for the study: Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry Funding: Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry Disclosure: All authors have declared no conflicts of interest. 141PD Bacoside A induced Sub-G0 arrest and early apoptosis in human glioblastoma cell line U-87 MG through notch signaling pathway M.G.S. Aithal, R. Narayanappa Department of Biotechnology, Dayananda Sagar College of Engineering, Bangalore, India Background: Glioblastoma multiforme (GBM) is the most common and highly malignant brain tumor with a poor prognosis of less than a year despite advance treatment facilities. Among many cell signaling pathway genes that show genetic alterations, aberrant expression of Notch pathway genes occurs frequently in GBM thus presenting novel therapeutic targets. Various herbal products having anticancer properties are being used in adjuvant therapy that are nontoxic and affordable compared to highly toxic and expensive chemotherapeutics. Bacopa monnieri has been used in Ayurveda for brain cell development because of its neuroprotective properties. Its anticancer properties have proved to be promising in treating cancers. Methods: This study is an attempt to evaluate the anticancer properties of Bacoside A, a component of Bacopa monnieri on GBM cell line U-87 MG and determine its effect on expression of Notch pathway genes. Flow cytometry analysis was carried out to study cell cycle arrest and apoptosis. Expression patterns of eight Notch pathway genes including Notch receptors (Notch1, Notch2, Notch3 and Notch4), ligands (Jagged1and Jagged2), downstream target (HES1) and a component of gamma-secretase complex (APH1A) were studied by quantitative real-time PCR. Results: Bacoside A showed considerable cytotoxicity on U-87 MG cell line causing cell cycle arrest and apoptosis. Cell cycle analysis showed an appreciable arrest of 39.21% cells in Sub-G0 phase at 80mg/ml concentration, further increasing to 53.21% at the higher concentration of 100mg/ml. The percentage of early apoptotic cells was low (3.48%) for untreated cells which increased substantially to 31.36% and 41.11% after 80mg/ml and 100mg/ml of Bacoside A treatment respectively. Further, the expression of Notch1 gene decreased with a fold change of 0.05 after exposure to Bacoside A, whereas the expression of HES1 gene increased by 25 fold. Conclusions: These data suggest that Bacoside A has a potential anticancer activity inducing cell cycle arrest and apoptosis via Notch signaling pathway in GBM in vitro. Legal entity responsible for the study: Department of Science and Technology Funding: Department of Science and Technology Disclosure: All authors have declared no conflicts of interest. 142PD Methods: A retrospective analysis was performed on 25 patients of recurrent glioblastoma, reirradiated with concurrent temozolomide between 2010 to 2015. All treatment decisions were based on interdisciplinary meeting. Survival time was calculated using the Kaplan-Meier method. Univariate and multivariate analysis were done using cox regression method. Characteristics of the 25 patients diagnosed were as follows: 18 men, 7 women; median age, 52 years (range, 20-65). At recurrence, 12 patients underwent both surgery and reirradiation, while 13 patients underwent radiation only. During reirradiation, 2 patient received stereotactic radiosurgery; 14 hypofractionated stereotactic radiation therapy (15-40 Gy in 3-5 fractions); 9 conventionally fractionated stereotactic radiation therapy (45-54 Gy in 25-27 fractions). All patient received temozolomide (either adjuvant or concurrent followed by adjuvant). 7 patient had MGMT methylated while 8 patient had non methylated tumours. Results: At the time of recurrence, median Karnofsky Performance Score (KPS) was 70% (range, 40-90). Median follow-up from recurrence was 12 months (range, 1-47.8 months). Median overall survival (OS) from recurrence was 15.26 months (95% confidence interval [CI], 10-20.33 months). None of the factor analysed (age, sex, gross tumour volume at time of recurrence, KPS, MGMT, time of recurrence) were significant for outcomes. No grade III or above acute or late complications arose due to reirradiation, and all patients completed planned course of radiation therapy. Conclusions: Our results suggest that reirradiation with high precision radiotherapy along with temozolamide is an effective option in patients with recurrent glioblastoma. Legal entity responsible for the study: Medanta The Medicity Funding: N/A Disclosure: All authors have declared no conflicts of interest. 143PD Hypofractionated radiotherapy combined with temozolomide for large brain metastases: A prospective trial Y. Ma, J. Xiao, N. Bi, Q. Liu, Y. Zhang, D. Liu, R. Zhao Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China Background: A phase II trial was conducted to investigate the feasibility and safety of hypofractionated radiotherapy combined with temozolomide (TMZ) for large brain metastases (BMs). Methods: Patients with BMs larger than 3cm or 6cc were enrolled. Radiotherapy (RT) was given by 52-52.5Gy/3.5-4Gy/13-15f. TMZ was administrated 75mg/m2 concurrently, followed by 6 cycles of adjuvant TMZ (150mg/m2/d, d1-5, q28d). Patients received MRI after 10-13 fractions of RT and would get replanned if GTV decreased>20%. The response was assessed after 2-3 months from treatment according to RTOG9508 criteria. Toxicity was recorded according to RTOG and CTCAE, v4.0 criteria. The primary end point was objective response Rate (ORR), and the secondary end points were local control (LC), intracranial progression-free survival (IPFS) and overall survival (OS) and toxicities. Results: From 2010 to 2015, 33 patients (Male: female¼20:13) were analyzed. The median age was 56 years old (range, 39-74). The major primary diagnosis was nonsmall cell lung cancer (57.6%). The number of large BMs were 38, and median GTV was 15.3cc (5.7-142.8cc). The median KPS score before and after treatment were 70 and 80. Median follow-up time of 30.0 months (range, 5.8-54.2 months) and ORR was [1]97.0%. 1-year LC, IPFS and OS were 95.2%, 69.5%, and 61.5%, respectively. Median survival time was 15.3 months. 22 patients (66.7%) acquired replanning during the treatment, and the median GTV decrease rate was 44.3% (21.1%-87.8%). The main toxicities were grade 1-2 nausea and vomiting, 1 patient got grade 3 liver-function impairment. Conclusions: Hypofractionated radiotherapy with TMZ represents a safe and effective option for patients with large BMs. More than 50 percent patients may need replanning to reduce damage of normal tissue and shorten treatment period. Clinical trial indentification: NCT02654106 Legal entity responsible for the study: N/A Funding: Beijing Hope Marathon Special Fund (LC2011A07) Disclosure: All authors have declared no conflicts of interest. Reirradiation for glioblastoma with temozolomide: Delicate balance between effectiveness and toxicity 144PD D. Gupta, T. Kataria, S.S. Bisht, S. Goyal, T. Basu, A. Abhishek, K. Narang, S. Banerjee Radiation Oncology, Medanta Cancer Institute, Medanta The Medicity, Gurgaon, India Background: The outcome of patients with recurrent glioblastoma is dismal despite the use of multimodality treatment. To asses the efficacy of high precision reirradiation with temozolomide as a salvage in patients with recurrent Glioblastoma. Volume 27 | Supplement 9 | December 2016 Cranio-Spinal irradiation – is acute hematological toxicity under-reported? A single institutional experience P. Thakur1, N. Kumar2, R. Miriyala2, S. Ghoshal1 Radiotherapy, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, 2Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India 1 Background: To analyze treatment interruptions due to acute hematological toxicity in patients of medulloblastoma receiving cranio-spinal irradiation (CSI). doi:10.1093/annonc/mdw578 | ix43 abstracts Methods: Case records of 52 patients of medulloblastoma treated between 2011 and 2014 were retrospectively analyzed for hematological toxicity and treatment interruptions. In our department, blood counts are monitored twice a week during CSI and spinal fields are interrupted for patients with grade II hematological toxicity. Spinal irradiation is resumed after recovery to grade I level (TLC > 3000; platelet count > 75,000). Results: Median age was 11 years. All patients received adjuvant CSI of 36 Gy, followed by boost of 18 Gy to posterior fossa, at 1.8 Gy per fraction. Concurrent chemotherapy was not given. Adjuvant chemotherapy was given after CSI. Spinal fields were interrupted in 73.1% of patients. Cause of first interruption was leucopenia in 92.1%, thrombocytopenia in 2.6%, and both in 5.3%. Median number of fractions at first interruption was 8.5, with 63.2% of interruptions before 10 fractions. Median duration for hematological recovery was 10 days. Half of the patients had at least two interruptions, and 20% subsequently developed grade III toxicity. Overall treatment time >50 days was seen in 24.5% patients. On multivariate analysis, significant correlation with duration of delay was observed for pre-treatment hemoglobin (p ¼ 0.018), number of fractions at first interruption, grade and duration of recovery of leucopenia (p < 0.0001). Conclusions: Acute hematological toxicity with CSI is frequently under-reported. Even after interrupting spinal irradiation at grade 2 levels, 20% of patients developed grade III toxicity subsequently. Increasing OTT may lead to poorer survival. Frequent monitoring and timely intervention for acute hematological toxicity are recommended during CSI. Legal entity responsible for the study: PGIMER Funding: PGIMER Disclosure: All authors have declared no conflicts of interest. 145P Outcomes of treatment of glioblastoma multiforme: A single institution experience from South India A.S. George1, A. Philip2, D. Poorna3, D. Makunny3, A. Pillai4, B. M.r5, R. Pillai2, W. Jose3, K. Pavithran2 1 Medical Oncology, Amrita Institute of Medical Sciences, Kochi, India, 2Medical Oncology, Amrita Institute of Medical Sciences, Cochin, India, 3Radiation Oncology, Amrita Institute of Medical Sciences, Cochin, India, 4Neurosurgery, Amrita Institute of Medical Sciences, Cochin, India, 5Pathology, Amrita Institute of Medical Sciences, Cochin, India Background: Glioblastoma multiforme(GBM) is the most common primary tumor of brain in adults.Radiotherapy (RT)plus concomitant and adjuvant temozolamide treatment is the current standard therapy for newly diagnosed GBM.The aim of our study is to analyse the clinical results and prognostic factors of GBM patients treated by post operative RT and concomitant Temozolamide followed by adjuvant temozolamide in a low income nation. Methods: We retrospectively evaluated 143 patients with GBM, treated in our institution from April 2006 to June 2015.Demographic and disease characteristics were recorded. Primary endpoint of the study was Overall survival(OS) and secondary endpoint was Progression Free Survival(PFS).OS was studied with respect to various variables including sex, ECOG score, extent of surgery, presentation with or without seizures, and number of adjuvant cycles of temozolamide(<6 versus 6) .OS and PFS were determined by the Kaplan-Meier method.The survival curves were compared by the log rank test. Results: Median age at presentation was 52 years(range 18-77 years).Male to female ratio of 1.74:1.All 143 patients underwent surgery with 22 patients(15.4%)having a biopsy alone,28(19.6%) partial resection and 93(65%) complete resection. All patients received RT, 25 did not complete prescribed 60 Gy either due to toxicity or disease progression. 88.1% received concomitant temozolamide, and 15(10.5%) completed less than 75% of the planned dose of temozolamide due to toxicity. Median OS was 13.8 months(95% CI 10.8 - 16.7).On univariate analysis, sex or seizures at presentation did not affect survival, but better survival outcome was seen with performance status 2 (p ¼ 0.011), complete resection(p < 0.001) and completion of 6 cycles of adjuvant temozolamide (p < 0.001).Median PFS was 11.76 months (95% CI 9.5-14.0).The 1 year OS was 55.7% and 2 year OS was 27.4%. Conclusions: Our single institution experience demonstrates that adherence to globally accepted guidelines for treatment and management of gliobastoma multiforme, gives similar results to that in literature.Good PS, lack of residual disease and completion of 6 cycles of adjuvant temozolamide are factors predicting a favourable outcome. Legal entity responsible for the study: Institutional Review Board, Amrita Institute Of Medical Sciences Funding: Amrita Institute Of Medical Sciences Disclosure: All authors have declared no conflicts of interest. ix44 | abstracts Annals of Oncology 146P Tolerability and pharmacokinetics (PK) of ABT-414 in Japanese patients (pts) with recurrent malignant glioma Y. Narita1, M. Nagane2, N. Kagawa3, K. Mishima4, T. Yamamoto5, T. Wakabayashi6, T. Hamada7, R. Odagawa7, Y. Nishimura7, T. Kiriyama7, H. Xiong8, C. Ocampo9, R. Nishikawa4 1 Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan, 2Department of Neurosurgery, Kyorin University Faculty of Medicine, Tokyo, Japan, 3Neurosurgery, Osaka University Hospital, Osaka, Japan, 4 Department of Neuro-Oncology/Neurosurgery, Saitama International Medical Center, Saitama-ken, Japan, 5Neurosurgery, University of Tsukuba Hospital, Ibaraki, Japan, 6Neurosurgery, Nagoya University Hospital, Aichi, Japan, 7 Development, AbbVie GK, Tokyo, Japan, 8R4PK, AbbVie, North Chicago, IL, USA, 9R48K, AbbVie, North Chicago, IL, USA Background: Pts with glioblastoma (GBM; WHO grade IV) have a poor prognosis. Epidermal growth factor receptor amplification (EGFR amp) is present in 50% of GBM, resulting in a unique protein conformation of EGFR that can be targeted by an antibody-drug conjugate, ABT-414. ABT-414 is comprised of an antibody, ABT-806, which targets EGFR amp, and a toxin, monomethyl auristatin F (MMAF). ABT-414 is internalized by tumor cells and MMAF is released, resulting in cell death. Here we report tolerability and PK of ABT-414 alone and with radiation therapy (RT) and temozolomide (TMZ) in Japanese pts. Methods: Study M13-714 (NCT02590263) is a non-randomized, open-label, Phase 1/2 study in Japanese pts. Phase 1, Arm A evaluates tolerability and PK of ABT-414 only in WHO grade III-IV recurrent glioma (rGBM); Arm B evaluates ABT-414 þ RT/TMZ in newly diagnosed pts. Phase 2 assesses efficacy of ABT-414 þ TMZ in EGFR amp, rGBM. Presented here are Phase 1, Arm A results (3 þ 3 dose escalation; 0.5-1.25 mg/kg, i.v. every 2 weeks), and preliminary Phase 1, Arm B results. Results: As of June 13, 2016, 10 pts were enrolled. Arm A, n ¼ 9 pts at 3 doses: 0.5 mg/kg (n ¼ 3); 1.0 mg/kg (n ¼ 3); 1.25 mg/kg (n ¼ 3). Arm B, n ¼ 1 pt at 1.0 mg/kg þ RT/TMZ. In Arm A, 6 pts were screened for EGFR amp; 2/6 (33%) were positive. The most common treatment emergent adverse events (TEAEs, 1 pt) were ocular-related, keratopathy (4/10, 40%) as most prevalent. Other TEAEs were increased ALT/AST levels (4/10, 40% each) and decreased platelet count and corneal injury (2/10, 20% each). The most common Grade 3/4 TEAEs were corneal erosion, keratitis, decreased platelets and malignant neoplasm progression (1 pt, 10% each). Four pts had stable disease (SD), with 1 pt (EGFRþ) maintaining SD for 40 weeks. Preliminary PK analysis for ABT-414 and ABT-806 was done on 7 pts (0.5 mg/kg, n ¼ 2; 1.0 mg/kg, n ¼ 3; 1.25 mg/kg, n ¼ 2), and for cys-mcMMAF on 5 pts (0.5 mg/kg, n ¼ 2; 1.0 mg/kg, n ¼ 3). Cmax (maximum serum concentration) and AUC14day (area under the curve, drug concentration vs time) were approximately dose-proportional for ABT-414 and cysmcMMAF. Conclusions: ABT-414 displayed acceptable tolerability and PK profile in Japanese pts, suggesting that it may be a novel therapy for those in need of better treatments. Clinical trial indentification: NCT02590263 Legal entity responsible for the study: AbbVie, Inc. Funding: AbbVie, Inc. Disclosure: Y. Narita: Honoraria (lecture fees) from Chugai Pharmaceutical Co., MSD; research funding from Nihon Medi-Physics Co. and AbbVie GK. M. Nagane: Honoraria: Chugai, MSD KK, Eisai, Otsuka, Novartis, Ono, Bayer Schering, Nobelpharma, AbbVie, Novocure. Research funding: Daiichi Sankyo, Chugai, MSD KK, Eisai, Kyowa Hakko Kirin, AbbVie, Ono, Mitsubishi Tanabe, Pfizer. Gifts: DaiichiSankyo, AbbVie GK. T. Wakabayashi: Contributions from Pfizer. T. Hamada, R. Odagawa, Y. Nishimura, T. Kiriyama, H. Xiong, C. Ocampo: Employee of AbbVie and may own stock. R. Nishikawa: Honoraria from Chugai Pharmaceutical Co., MSD, Eisai, Novocure and AbbVie. All other authors have declared no conflicts of interest. 147P Midline crossing grade I to grade III gliomas: Impact of high dose XRT on survival K. Mushtaq1, S. Butt2, T. Mehmood1 Radiation Oncology, Shaukat Khanum Memorial Cancer Hospital and Reserch Centre (SKM), Lahore, Pakistan, 2Radiotherapy, Shaukat Khanum Memorial Cancer Hospital and Reserch Centre (SKM), Lahore, Pakistan 1 Background: Midline crossing gliomas are known to have a dismal prognosis across the globe. There is a paucity of literature on standard radiotherapy regimens for their management. Our study, primarily, aims to evaluate the significance of escalated radiotherapy doses. In addition, the significance of size and enhancement at initial imaging, as prognostic factors of overall survival. Methods: For our retrospective study, we identified 34 patients with Grade I to III midline crossing gliomas, treated at Shaukat Khanum Memorial hospital, from 2005 till 2010. 22 males and 12 females, aged 23 to 59 years, were randomized into four groups, based on the dose of radiotherapy received. They were 60Gy/30#, 56Gy/28#, 48Gy/16# and 30Gy/10#. Their frequencies were 52.9%, 8.8%, 23.9% and 14.7% respectively. The Volume 27 | Supplement 9 | December 2016 Annals of Oncology histologies included were Astrocytomas, Oligodendrogliomas and Ependymomas. With respect to initial tumor size, four groups were identified. Patients with 10-29mm, 3049mm,50-69mm and 70-90mm tumors. Their respective frequencies were 14.7%,41.2%,17.6% and 26.5%. 55.9% had enhancing tumors and 44.1% had non enhancing tumors. The outcome compared was 5 years overall survival in the four radiotherapy groups. In addition, difference in overall survival, according to tumor size and enhancement at initial imaging, was evaluated. Results: The overall survival was found to be 36% at 5 years and 18% at 9 years. At 5 years, the overall survival for patients who received 60Gy/30#, 56Gy/28#, 48Gy/16# and 30Gy/ 10# was found to be 32%, 62%, 22% and 20% respectively. In summary, the overall survival for patients who received >50Gy was 36% as compared to 20% for patients with <50Gy dosage. In comparing 5 years overall survival with respect to initial tumor size, the four groups 10-29mm, 30-49mm, 50-69mm and 70-90mm had overall survival of 60%, 32%, 21% and 10% respectively. 5 years overall survival of patients with non enhancing tumors was found to be 42%. It was 20% for patients with enhancing tumors. Conclusions: The overall survival of patients with midline crossing gliomas is significantly improved with higher radiotherapy doses, while increasing size and enhancement in tumors negatively affect it. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 148P Primary CNS lymphoma – Our experience with this rare disease A. Pathak, A. Kapoor Medical Oncology, Army Hospital Research & Referal, Delhi, India Background: Primary CNS lymphoma (PCNSL) is an an uncommon variant of extranodal non-Hodgkin lymphoma (NHL) arising exclusively in the CNS, that is, the Volume 27 | Supplement 9 | December 2016 abstracts brain parenchyma, spinal cord, eyes, cranial nerves, and/or meninges. It is a highly aggressive malignancy. This lymphoma represents 4% of intracranial neoplasms and 4%-6% of all extranodal lymphomas. The standard chemotherapy regimensfor treatment of systemic lymphoma (eg, CHOP), are either ineffective or too toxic. The definitive treatment of PCL is not known and there is a lot of institutional variation. Here we present our experience of managing 10 cases of PCNSL in immunocompetent patients, their initial presentation, diagnosis and their treatment. Methods: We treated 10 patients in our tertiary care centre in the last year. The complete staging work up was done to exclude any other systemic lymphoma by whole body CECT scan, ophthalmologic evaluation (including slit-lamp examination), CSF studies, bone marrow biopsy, USG tests. Treatment given was on the basis of standard protocols. Results: We treated 10 patients in our tertiary care centre in the last year. We had two patients, one of 30 years and the other of 32 years, and the rest were older than 60 years. All the patients presented with headache and 60% (6/10) had instability of gait and 40% (4/10) had hemiparesis. Only 20% (2/10) had features of raised intracranial tension and one presented with vitreous haemorrhage. On MRI, there was a single lesion in 50% (5/10). The distribution of the solitary lesion was hemispheres 50% (5/10), periventricular 60% (6/10), thalamus/basal ganglia 40% (4/10), corpus callosum 20%, (2/10) and cerebellum (10%) (1/10). On histopathology 90% were diffuse large B cell lymphoma (9/10) and 10% (1/10) was T cell-rich B cell lymphoma (IHC – CD20þ, LCAþ, CD3þ). Conclusions: Though there has been no clear evidence as to the best management protocol, we observed that the addition of second agent was entirely dependent on the clinical status of the patient. However with expansion of molecular biology and improvement in diagnostic sensitivity and specificity in coming years we can perhaps reduce the dilemma of dose intensive versus de-escalation therapy in management of PCNSL. Legal entity responsible for the study: N/A Funding: Indian Army Disclosure: All authors have declared no conflicts of interest. doi:10.1093/annonc/mdw578 | ix45 Annals of Oncology 27 (Supplement 9): ix46–ix51, 2016 doi:10.1093/annonc/mdw579 Developmental therapeutics 149O The National University Cancer Institute, Singapore (NCIS) Integrated Molecular Analysis of Cancer (IMAC) precision oncology programme: Frequency of actionable mutations and outcomes following matched therapy in an Asian Cancer Centre abstracts N. Syn1, V. Heong1, X.W. Lee1, N.S. Sapari2, X.Q. Koh2, Z. Fazreen2, J.S.Y. Lim2, B. Pang3, D. Lim3, A.L-A. Wong1, R.A. Soo1, W-P. Yong1, C-E. Chee1, S-C. Lee1, B-C. Goh1, R. Soong2, D.S. Tan1 1 Department of Haematology-Oncology, National University Cancer Institute, Singapore, 2Centre for Translational Research and Diagnostics, Cancer Science Institute of Singapore, Singapore, 3Department of Pathology, National University Health System, Singapore Background: Limited data exists on outcomes of precision oncology studies using multimarker molecular screening for biomarker-enriched early-phase clinical trials in Asia. The IMAC programme (NCT02078544) is one of the first precision oncology protocols initiated in Asia with the aim of assessing the feasibility and potential value of this approach. Methods: Tumour samples from pts with advanced/recurrent malignancies referred to the NCIS Developmental Therapeutics Unit (DTU) were prospectively screened for 2,800 COSMIC mutations in 50 cancer genes using the Ion AmpliSeqTM Cancer Hotspot Panel v2, and results were used for therapeutic decision-making. Information was collected on reported variants, treatment details and patient outcomes. Results: From April 28, 2014, to July 18, 2016, IMAC enrolled 192 pts with diverse tumour types, including gynaecological (26%), colorectal (18%), breast (11%) and lung cancers (11%). Next-generation sequencing was feasible in 175 pts (91%), achieving a mean depth of 1,990 reads and uniformity of 96%. Median time between sample receipt to return of results was 36 days (interquartile range [IQR], 21–47). Reportable mutations were found in 142 of 175 pts (81%), and potentially actionable mutations were most frequently reported in TP53 (51% of 142 pts), PIK3CA (23%), KRAS (20%) and PTEN (8%). Ten EGFR-mutant NSCLC pts (7%) received an approved EGFR TKI, and 16 pts (11%) were enrolled into a matched biomarker-enriched clinical trial (PI3K/ PTEN/AKT, N ¼ 12; ALK, N ¼ 2; AKT, N ¼ 1; EGFR, N ¼ 1), with the latter pts showing durable clinical benefit (median PFS: 3.7 months, IQR: 1.8–5.5; median OS: 16.4 months, IQR: 6.5–20.3). Conclusions: Multi-marker molecular screening of cancer pts in the IMAC protocol for therapeutic prioritisation is feasible, shows early evidence of clinical benefit, and is currently supporting a range of ongoing precision oncology studies at our centre. IMAC provides useful data which may aid similar Asian initiatives. Clinical trial indentification: NCT02078544 Legal entity responsible for the study: Domain Specific Review Board (DSRB), National University Hospital Funding: National Medical Research Council (NMRC) Disclosure: All authors have declared no conflicts of interest. 150O Clinical safety and activity from a phase 1 study of LOXO-101, a selective TRKA/B/C inhibitor, in solid-tumor patients with NTRK gene fusions D.S. Hong1, A. Dowlati2, H.A. Burris III, 3, J.J. Lee4, M.S. Brose5, A.F. Farago6, T.M. Bauer3, M. Taylor7, A.T. Shaw6, S. Smith8, N. Nanda8, S. Cruickshank8, M.C. Cox8, R. Doebele9 1 Department of Investigational Cancer Therapeutics, MD Anderson Cancer Center, Houston, TX, USA, 2Hematology/Oncology, University Hospitals Case Medical Center, Cleveland, OH, USA, 3Drug Development, Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN, USA, 4Medical Oncology and Hematology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA, 5 Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA, USA, 6Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA, 7Hematology/Oncology, Oregon Health Science University, Portland, OR, USA, 8Clinical Development, Loxo Oncology, Inc, South San Francisco, CA, USA, 9Medical Oncology, University of Colorado Denver, Denver, CO, USA Background: NTRK1, 2 and 3 gene fusions occur across a wide array of tumors. LOXO101 is an orally bioavailable, potent, ATP-competitive, selective pan-TRK inhibitor. Here, we report response and durability data for patients with NTRK fusions enrolled in an ongoing Phase I dose escalation trial. Updated pharmacokinetic (PK) and safety data for all enrolled patients (pts) are also reported. Methods: This is an ongoing, open-label, multicenter, 3 þ 3 dose escalation Phase I study. LOXO-101 is administered orally as a one- or twice-daily dose for continuous 28day cycles. Response is measured by RECIST. Plasma is obtained for PK analysis. Safety information is collected on all patients and reported regardless of their attribution to the study drug. Results: As of March 25, 2016, 43 pts with solid tumors have been enrolled, including seven pts with NTRK fusions across five different tumor types. Six of the seven patients were evaluable for response and all six have demonstrated a clinical response to LOXO101. Five of six patients (83%) have achieved confirmed RECIST partial responses. All seven patients remain on study with a duration of therapy from one to fourteen cycles. No objective anti-tumor activity has been observed in treated patients without an NTRK fusion. In total, 43 pts have been treated across five dose levels. Maximum plasma concentrations of LOXO-101 were reached 30-60 minutes following dosing. The unbound drug levels of LOXO-101 appear sufficient for approximately 98% inhibition of TRKA/B/C at peak concentrations at all dose levels. LOXO-101 has been well tolerated. The maximum tolerated dose has not been reached, and the most common adverse events are Grade 1 and 2 fatigue (33%), constipation (23%) and dizziness (23%). Conclusions: LOXO-101 has been well tolerated and has shown promising and broad anti-tumor activity in patients with NTRK fusions. All patients with NTRK fusions have experienced objective tumor reductions and remain on study without disease progression. These data suggest that a LOXO-101 dose of 100mg BID is well-tolerated and capable of inducing durable disease control in patients with NTRK gene fusions. Clinical trial indentification: NCT02122913 Legal entity responsible for the study: Loxo Oncology, Inc. Funding: Loxo Oncology, Inc. Disclosure: D.S. Hong: Travel paid for by Loxo Oncology, Inc. S. Smith, S. Cruickshank: Consultant fees paid by Loxo Oncology, Inc. N. Nanda, M.C. Cox: Employee and stockholder of Loxo Oncology, Inc. R. Doebele: Research grant provided by Loxo Oncology, Inc. All other authors have declared no conflicts of interest. 151O Preclinical characterization of alofanib, a novel allosteric FGFR2 inhibitor I. Tsimafeyeu1, E. Stepanova2, D. Khochenkov2, G. Murillo3, N. Lapina4, E. Gavrilova5, M. Byakhov6, S. Tjulandin7 1 Moscow office, Kidney Cancer Research Bureau, Moscow, Russian Federation, 2Laboratory of Biomarkers and Tumor Angiogenesis, N. N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation, 3Research Institute, Illinois Institute of Technology, Chicago, IL, USA, 4Laboratory of toxicology and pharmacology, Institute of Toxicology of Federal Medical-Biological Agency, St. Petersburg, Russian Federation, 5Spb Office, Ruspharmtech LLC, Saint Petersburg, Russian Federation, 6Department of Chemotherapy, Moscow Clinical and Research Center, Moscow, Russian Federation, 7Department of Clinical Pharmacology and Chemotherapy, N. N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation Background: Alofanib (RPT835) is a novel selective allosteric inhibitor binding to the extracellular domain of FGFR2. Here, we report preclinical pharmacology and toxicity of alofanib. Methods: To assess the efficacy of alofanib on FGF-mediated cell proliferation, SKOV3 (ovarian cancer), SUM52PE (triple negative breast cancer), HS578T (triple negative breast cancer), HUVEC (endothelial), and hFOB (osteoblast) cells were treated with serially diluted alofanib. Studies in xenograft models were performed using SKOV3, SUM52PE, HS578T, NCI-H226 (lung cancer), and HCT116 (colon cancer) cells with different levels of FGFR2 expression. Mice were randomized into treatment and vehicle groups. In ovarian cancer study, alofanib was used in combination with carboplatin/ paclitaxel i.v. or orally. Three preclinical pharmacokinetic (PK) studies were conducted to evaluate properties of alofanib (gavage; capsules, i.v. injections). 240 rats and 30 rabbits received alofanib (0–40.5 and 0–21.6 mg/kg/day) i.v. daily for 24 weeks. Clinical observations and laboratory parameters were recorded. Necropsy was conducted following treatment/recovery periods, and histologic examinations were performed. Results: Alofanib significantly inhibited proliferation of FGFR2-expressing cells. Alofanib potently inhibited growth of cells expressing FGFR2 IIIb and IIIc, with GI50 values of 12 and 16 nmol/l, respectively. In preclinical xenograft models, alofanib significantly inhibited aggressive growth of FGFR2 high-expressing SUM52PE breast cancer and SKOV3 ovarian cancer, and had moderate activity in the FGFR2 lowexpressing HS578T breast cancer. Treatment with alofanib did not result in the FGFR2negative NCI-H226 lung cancer and HCT116 colon cancer growth. There was no treatment-related mortality, severe toxicity and significant changes in organs in the 24week study. Compound was well-tolerated in vivo. Mild hyperphosphatemia was found C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts Annals of Oncology in female rats. Alofanib suppressed spermatogenesis in male rats. Blood vessel wall inflammation may be caused by alofanib. PK data will be presented at the meeting. Conclusions: These results provide strong rationale for evaluation of alofanib in patients with FGFR2-expressing cancers. Legal entity responsible for the study: N/A Funding: Skolkovo Foundation Disclosure: E. Gavrilova: Employer. All other authors have declared no conflicts of interest. 152O A phase 1, first-in-human dose escalation study of ETC-159 in advanced or metastatic solid tumours V. Teneggi1, M. Ng2, D.S. Tan3, V. Subbiah4, C. Weekes5, V. Diermayr1, K. Ethirajulu1, P. Yeo1, D. Chen1, S. Gan1, S. Blanchard1, R. Nellore1, M.A. Lee6, J. Hill6, D. Virshup7, B. Madan7, A. Matter6 1 D3(Drug Discovery and Development), A*STAR, Singapore, 2Department of Medical Oncology, National Cancer Center, Singapore, 3Department of Haematology-Oncology, National University Hospital (NUH), Singapore, 4 Investigational Cancer Therapeutics, MD Anderson Cancer Center, Houston, TX, USA, 5School of Medicine, University of Colorado Denver, Denver, CO, USA, 6ETC(Experimental Therapeutic Centre), A*STAR, Singapore, 7Graduate Medical School, Duke-National University of Singapore (NUS), Singapore Background: ETC-159 is a small molecule selectively inhibiting the O-acyltransferase PORCN (porcupine) that is required for the palmitoylation of all Wnts. Preclinical studies show anti-tumour effects when administered orally using different dosing schedules. In this first-in-human study we investigate safety, tolerability, maximum tolerated dose (MTD), pharmacokinetic (PK) and pharmacodynamic (PD) of ETC-159 in patients (pts) with advanced or metastatic solid tumours. Methods: Pts with no other treatment options and adequate organ function are eligible. ETC-159 is administered orally, once every other day in a cycle of 28 days. Doses are escalated according to an ordinal continual reassessment method (oCRM) with a dose limiting toxicity (DLT) period of 28 days. PK and PD (Axin2mRNA levels) are assessed on day 1 and day 15 of cycle 1 and on day 1 of cycle 2. Response is assessed every 2 cycles using RECIST 1.1 Results: This is the initial report of a Phase 1 open-label, multicentre study of ETC-159. As of 12 August 2016, 10 pts have been enrolled: 1mg (2pts), 2mg (2pts), 4 mg (3 pts), 8 mg (3pts); 70% were male, mean age (range) was 56 (40-68) yrs. Tumour types were colorectal cancer (9) and renal cancer (1). Eight pts discontinued due to disease progression. The most common adverse events (AEs 3 pts) were: Anorexia (4 pts, grade 1-2), Fatigue (3 pts, grade 1-2), Lethargy (3pts, grade 1-2), Constipation (3pts, grade 1-2). No treatment-related serious AEs or DLTs were observed. Dose escalation is ongoing at the 8mg dose. At 4 mg (n ¼ 2), PK on day 1 showed mean Cmax, AUC last, and T1/2 of: 123 ng/mL, 2540ng*hr/mL and 14 h, respectively. To date, no complete responses (CR) or partial responses (PR) were observed. One pt at 2 mg and 1 pt at 4 mg remained in the study in stable disease for 6 cycles; the patient at 4 mg is still ongoing (with 1 pt in cycle 1 at 8 mg). Axin2 levels, measured in hair follicles, showed reduction in 4 out of 7 pts treated at 1, 2 and 4 mg of ETC-159. Conclusions: ETC-159 as a single agent has been safe and well-tolerated. No CR or PR but disease stabilisation was observed. Target engagement was observed at all dose levels explored. Dose escalation is ongoing. Clinical trial indentification: NCT02521844. Legal entity responsible for the study: D3(Drug Discovery and Development), A*STAR, Singapore Funding: D3(Drug Discovery and Development), A*STAR, Singapore Disclosure: V. Teneggi, P. Yeo: Employment at D3, the sponsor of the study. V. Diermayr, K. Ethirajulu, D. Chen, A. Matter: Employment at D3, the sponsor of the study. S. Gan, S. Blanchard, R. Nellore: Employment at D3, sponsor of the study. D. Virshup, B. Madan: Holds IP rights in the ETC-159 project. All other authors have declared no conflicts of interest. 153P Ramucirumab safety in East Asian (EA) compared to non-EA patients: A meta-analysis of adverse events (AEs) in 6 global, randomized, double-blind, phase 3 clinical trials H.C. Chung1, Y. Chao2, K-W. Lee3, M. Kudo4, C-J. Yen5, T.W. Kim6, K. Yamazaki7, J-Y. Shih8, S-W. Kim6, J-H. Sohn1, R. Cheng9, Y. Zhang10, P. Binder10, G. Mi11, M. Orlando12, K. Muro13 1 Medical Oncology, Yonsei Cancer Center, Seoul, Republic of Korea, 2 Oncology, National Yang-Ming University and Taipei Veterans General Hospital, Taipei, Taiwan, 3Oncology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea, 4Oncology, Kinki University School of Medicine, Osaka, Japan, 5Oncology, National Cheng Kung University Hospital, Tainan, Taiwan, 6Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 7Oncology, Shizuoka Cancer Center, Shizuoka, Japan, 8Oncology, National Taiwan University Hospital, Taipei, Taiwan, 9Medical, Eli Lilly and Company, Taipei, Taiwan, 10 Medical, Eli Lilly and Company, Bridgewater, NJ, USA, 11Statistics - Oncology, Eli Lilly and Company, Indianapolis, IN, USA, 12Medical, Eli Lilly and Company, Buenos Aires, Argentina, 13Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan Background: Ethnicity may account for differences in pharmacokinetics or pharmacodynamics of drugs, leading to variability in drug response and tolerance. A meta-analysis was conducted to examine the incidence of AEs possibly associated with ramucirumab in EA compared to non-EA patients. Methods: Six global, randomized, double-blind, phase 3 registration trials investigating ramucirumab were assessed. Relative risk (RR) and 95% confidence intervals (CIs) were calculated for all-grade and grade 3 AEs using fixed-effects and mixed-effects models or pooled rate of events across trials, depending on heterogeneity of the trials and observation of rare AEs. Results: 4996 randomized patients received ramucirumab or placebo; 802 (16%) were EA (ramucirumab [N ¼ 411] and placebo [N ¼ 391]) and 4194 were non-EA (ramucirumab [N ¼ 2337] and placebo [N ¼ 1857]). In general, the patient baseline characteristics were balanced between treatment arms in EA and non-EA patients. Incidence rates and RR of AEs are presented in the Table. Grade 3 AEs possibly associated with ramucirumab occurring in 5% of both EA and non-EA patients were neutropenia (42.1% vs. 25.5%), hypertension (8.8% vs. 9.0%), and febrile neutropenia (6.1% vs. 7.0%). The ramucirumab incidence rates of all-grade proteinuria, bleeding, and neutropenia, and grade 3 neutropenia, were 5% higher in EA compared to non-EA patients. Conclusions: Despite differences in incidence rates of some AEs between EA and nonEA patients, in particular grade 3 neutropenia, there was no substantial difference between EA and non-EA patients in RR for AEs possibly associated with ramucirumab in these phase 3 trials. Legal entity responsible for the study: N/A Funding: Eli Lilly and Company Disclosure: H.C. Chung: Grants/Research Support from Lilly, GSK, Speakers Bureau/ Honoraria from Merck-Serono, Lilly and Consulting Fees from Taiho, Celltrion, MSD, Lilly, Quintiles, BMS. M. Kudo: Lecturer: Bayer, Kowa, Taiho Grants: Chugai, Otsuka, Takeda, Taiho, Sumitomo Dainippon, Daiichi Sankyo, MSD, Eisai. T.W. Kim: Grant: Roche, Bayer Honoraria: Amgen. K. Yamazaki: Speakers Bureau: Takeda, Chugai, Eli Lilly, Taiho, Yakult, Daiichi Sankyo, Merck Serono. J-Y. Shih: Speaking honoraria from AstraZeneca, Roche, Pfizer, Boehringer Ingelheim and Eli Lilly. R. Cheng, Y. Zhang, P. Binder: Full-time employee of Eli Lilly and Company. G. Mi, M. Orlando: Full-time employee of Eli Lilly and Company and stock ownership in Eli Lilly and Company. All other authors have declared no conflicts of interest. Table: 153P Incidence and relative risk of adverse events in completed phase 3 ramucirumab clinical trials. East Asians Non-East Asians Ramucirumab N ¼ 411 Hypertension Proteinuria Bleeding All-grade Grade 3 All-grade Grade 3 All-grade Grade 3 96 (23.4) 36 (8.8) 101 (24.6) 16 (3.9) 172 (41.8) 13 (3.2) Placebo N ¼ 391 RR [95% CI] Ramucirumab N ¼ 2337 Placebo N ¼ 1857 RR [95% CI] 24 (6.1) 5 (1.3) 30 (7.7) 0 (0.0) 74 (18.9) 15 (3.8) 3.6 [2.4, 5.5] 5.6 [2.4, 13.0] 3.1 [2.2, 4.5] 5.5 [1.7, 17.7] 2.2 [1.8, 2.8] 0.8 [0.4, 1.6] 489 (20.9) 210 (9.0) 158 (6.8) 15 (0.6) 859 (36.8) 61 (2.6) 143 (7.7) 52 (2.8) 40 (2.2) 1 (0.1) 352 (19.0) 47 (2.5) 2.6 [2.2, 3.1] 3.4 [2.5, 4.6] 3.4 [2.4, 4.7] 4.1 [1.3, 12.8] 1.9 [1.7, 2.1] 1.1 [0.8, 1.6] Continued Volume 27 | Supplement 9 | December 2016 doi:10.1093/annonc/mdw579 | ix47 abstracts Annals of Oncology Continued East Asians Ramucirumab N ¼ 411 GI bleeding GI perforation ATE VTE IRR IWH Neutropenia Febrile neutropenia All-grade Grade 3 All-grade Grade 3 All-grade Grade 3 All-grade Grade 3 All-grade Grade 3 All-grade Grade 3 All-grade Grade 3 All-grade Grade 3 36 (8.8) 9 (2.2) 5 (1.2) 5 (1.2) 3 (0.7) 1 (0.2) 11 (2.7) 3 (0.7) 17 (4.1) 0 (0.0) 2 (0.5) 0 (0.0) 218 (53.0) 173 (42.1) 25 (6.1) 25 (6.1) Non-East Asians Placebo N ¼ 391 RR [95% CI] Ramucirumab N ¼ 2337 Placebo N ¼ 1857 18 (4.6) 8 (2.0) 1 (0.3) 1 (0.3) 7 (1.8) 3 (0.8) 7 (1.8) 4 (1.0) 18 (4.6) 1 (0.3) 0 (0.0) 0 (0.0) 143 (36.6) 104 (26.6) 15 (3.8) 14 (3.6) 1.9 [1.1, 3.2] 1.0 [0.4, 2.3] 1.9 [0.6, 6.3] 1.9 [0.6, 6.3] 0.5 [0.2, 1.5] 0.5 [0.1, 2.1] 1.4 [0.6, 3.2] 0.8 [0.2, 2.3] 0.9 [0.5, 1.7] 0.6 [0.1, 2.8] 1.4 [0.3, 5.5] NA 1.5 [1.3, 1.7] 1.6 [1.4, 1.9] 1.5 [0.9, 2.7] 1.6 [0.9, 3.0] 150 (6.4) 36 (1.5) 25 (1.1) 23 (1.0) 35 (1.5) 20 (0.9) 95 (4.1) 53 (2.3) 163 (7.0) 28 (1.2) 12 (0.5) 5 (0.2) 775 (33.2) 596 (25.5) 166 (7.1) 163 (7.0) 85 (4.6) 28 (1.5) 6 (0.3) 5 (0.3) 33 (1.8) 16 (0.9) 109 (5.9) 57 (3.1) 86 (4.6) 12 (0.6) 4 (0.2) 0 (0.0) 550 (29.6) 380 (20.5) 85 (4.6) 84 (4.5) RR [95% CI] 1.5 [1.2, 2.0] 1.1 [0.7, 1.8] 3.0 [1.3, 6.9] 3.0 [1.3, 7.2] 0.9 [0.5, 1.4] 1.0 [0.5, 2.0] 0.7 [0.6, 1.0] 0.8 [0.5, 1.1] 1.5 [0.9, 2.6] 1.5 [0.8, 2.9] 1.7 [0.6, 4.5] 1.9 [0.5, 7.5] 1.3 [1.1, 1.6] 1.5 [1.2, 1.9] 1.6 [1.2, 2.1] 1.6 [1.2, 2.1] Abbreviations: ATE¼arterial thromboembolism; CI¼confidence interval; GI¼gastrointestinal; IRR¼infusion-related reaction; IWH¼impaired wound healing; NA¼not applicable as at least one patient must have had an event to calculate RR; RR¼relative risk; VTE¼venous thromboembolism. 154P Clinical trial designs for the approval of rare cancer drugs in Japan E. Noguchi1, K. Yonemori1, T. Shimoi1, M. Yunokawa1, H.S. Okuma2, A. Kawachi2, A. Kitano3, T. Nishikawa2, A. Shimomura2, C. Shimizu2, Y. Takiguchi4, A. Kawai5, Y. Fujiwara2, K. Tamura2 1 Breast and Medical Oncology/Rare Cancer Center, National Cancer Center Hospital, Tokyo, Japan, 2Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan, 3Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan, 4Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan, 5Rare Cancer Center, National Cancer Center Hospital, Tokyo, Japan Background: More attention has been focused on rare cancers in Japan, since the Japanese Cabinet launched the second term of the “Basic Plan for Promotion of Cancer Measures” in 2012. Patients with rare cancers are confronted with the challenge of diagnosis, treatment, research and drug development. This study aimed to characterize the clinical trial designs supporting drug approval for rare cancers. Methods: We examined the Japanese New Drug Applications (JNDA) for oncology indications which were submitted between April 2006 and March 2016 and were approved by the Ministry of Health, Labour and Welfare (MHLW). Pharmaceuticals indicated for symptom management and supportive care were excluded. The information concerning clinical data package for JNDA was obtained from publicly accessible review reports of the Pharmaceuticals and Medical Devices Agency. We defined rare cancers as those with an annual incidence of < 6/100,000 in Japan, adopting the Rare Cancers in Europe (RARECARE) definition. Results: A total of 182 oncology indications for 106 drugs were included. Ninety rare cancer indications (67 drugs) granted regulatory approval. Among them, 20 indications were approved based on available evidence without conducting clinical trials additionally. For remaining 70 indications were as follows: 39 for hematologic diseases, 8 for sarcoma, and malignant melanoma, 5 for central nervous system tumors, 3 for neuroendocrine tumors, 2 for ovarian cancer, cervical cancer, and malignant pleural mesothelioma, 1 for urothelial cancer, and medullary thyroid cancer (overlapping). Fifty indications were granted orphan designations and 15 indications developed at the request of the MHLW. There were 24 indications approved based on the results of noncomparative phase II trials, 3 based on randomized phase II trials, and 43 based on phase III trials. Thirteen out of 43 phase III trials were international clinical trials. Both endpoint measuring time to event endpoint (e.g. progression-free survival) and tumor shrinkage (e.g. response rate) were commonly used (34 and 31 indications, respectively). Conclusions: Wide variation exists in clinical trial designs supporting drug approval for rare cancers. Detailed investigation will give impetus for drug development in the area on rare cancers. ix48 | abstracts Legal entity responsible for the study: N/A Funding: National Cancer Center Disclosure: All authors have declared no conflicts of interest. 155P Randomized controlled trial of CT-guided versus laparoscopic radiofrequency ablation in recurrent small hepatocellular carcinoma against the diaphragmatic dome Q. Zheng1, H. Ding2, C. Zhu1, L. Wang2, Y. Wan3 Oncology, The second hospital affiliated to southeast university, Nanjing, China, 2Radiology, The second hospital Affiliated to Southeast University, Nanjing, China, 3Biomedical, Pennsylvania State University, University Park, PA, USA 1 Background: Radiofrequency ablation (RFA) have been used to treat hepatocellular carcinoma (HCC) in the subphrenic area. Very few studies focus on ablation of recurrent small HCC against the diaphragmatic dome. The therapeutic safety, efficacy, and hospital fee have never been compared between CT guided RFA and laparoscopic RFA (L-RFA) either. Methods: CT guided RFA and L-RFA were performed in totally 116 patients with 151 local recurrent HCC lesions abutting the diaphragm. We compared major and minor postoperative complications, hospital stay and fee, overall survival (OS), and local tumor progression (LTP) between two groups for evaluating respective therapeutic efficacy and safety. Moreover, in CTguided percutaneous RFA group, depending on the locations of recurrent HCC nodules differentiated puncture paths and ablation methods were used, and intraoperative complications were recorded Results: There is no significant difference in OS and LTP between CT-guided RFA and LRFA.In recorded postoperative complications, the morbidity in CT-guided RFA group is lower than that of L-RFA group. The average safety margin is 8 and 11 mm in CTguided RFA and LRFA group, respectively. The shoulder and back pain is significantly high in L-RFA group probably due to pneumoperitoneum. Moreover, overall hospital stay and cost is also lower in CT-guided RFA group. Conclusions: Both CT-guided RFA and L-RFA are considered to be an effective approach for recurrent small HCC abutting diaphragm. Particularly, CT-guided RFA is an easy and economic with less complications if suitable puncture paths and ablation methods can be applied. Legal entity responsible for the study: Huaiyin Ding, Chuandong Zhu, Lixue Wang, Qin Zheng, and Yuan Wan Funding: This work was partially supported by Nanjing Medical and Health Research Funding YKK15142, Natural Science Foundation of Jiangsu Province BK20141084, Key Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology Topics of Nanjing Medical Technology Development Project (ZKX13019), and Medical Research Program of Jiangsu Province H201440. Disclosure: All authors have declared no conflicts of interest. 156P Efficacy and safety of a novel nanosomal docetaxel lipid suspension (NDLS) as an anti cancer agent - a retrospective study M. Ashraf1, R. Sajjad2, M.A. Khan3, M. Shah4, Y. Bhat5, Z.A. Wani5 Department of Surgical and Clinical Oncology, Noora Hospital, Srinagar, India, 2 Department of Medical Oncology, Noora Hospital, Srinagar, India, 3Medical Affairs, Intas Pharmaceuticals Ltd, Ahmedabad, India, 4Department of Internal Medicine and Critical Care, Noora Hospital, Srinagar, India, 5Department of Gastroenterology, Noora Hospital, Srinagar, India Conclusions: In the molecular targeted drugs in phase I trials, the toxicities equivalent to DLT were mainly non-hematological and frequently observed in the chronic phase (i.e., after the 1st cycle). We need to establish the optimal evaluation period of DLT or equivalent toxicities for the molecular targeted drugs in phase I trials. Also, we need to translate this period for the toxicity evaluation of the immuno-therapeutic drugs that are increasing in development. Legal entity responsible for the study: National Cancer Center Hospital Funding: N/A Disclosure: All authors have declared no conflicts of interest. 1 Background: The NDLS (DoceAqualipTM) is a novel formulation approved in India for various solid tumors. With shorter infusion times without premedication, NDLS has demonstrated good response rates and better tolerability than conventional docetaxel. Methods: This retrospective study included adult patients with solid tumors (Eastern Cooperative Oncology Group performance status: 0-2) treated with NDLS between June 2014 and June 2016. NDLS was administered as 1-hour IV infusion every 3 weeks at a dose determined by the physician (range: 75-100 mg/m2) based on the tumor type. Endpoints: efficacy as a best overall response rate (ORR, complete response [CR] þ partial response [PR]), disease control rate (DCR, CR þ PR þ stable disease [SD]) evaluated using CT, MRI, USG, Tumor Marker or Status, and safety (incidence of adverse events [AEs] with toxicity grades). Results: Among 69 patients analyzed, 37 (54%) were men (mean age: 55.2 614.9 years). Majority had cancer stage III (54%) and IV (36%). Gastric adenocarcinoma was the most common (35%), followed by ovarian cancer (20%), and non-small cell lung cancer (19%). NDLS was administered in metastatic (42%) or neo-adjuvant (36%) setting. Of 56 patients evaluable for response, the best ORR was achieved in 33 (59%) patients (CR: 7 [13%], PR: 26 [46%], p < 0.0001). The DCR was 98% (p < 0.0001) and only 1 patient had PD. Median follow-up period was 13 weeks (range: 7-34 weeks). Among 45 (65%) patients with AEs, 66 episodes (all grades) of anemia along with neutropenia were observed. 41 episodes of isolated neutropenia and 15 episodes of anemia were noted. No granulocyte colony stimulating factor (GCSF) support was required with NDLS monotherapy. Dual/triplet chemotherapy (NDLS þ Platinum derivative/5FU/ gemcitabine/capecitabine): 2-3 doses of GCSF normalized counts; 1 patient on NDLS þ Carboplatin needed 6 doses. Nausea with vomiting was the most common nonhematological toxicity (all grades, 94 episodes). No events of peripheral neuropathy, allergic reactions, or deaths were reported. Conclusions: The NDLS demonstrated a promising overall response and was welltolerated following multiple doses (75-100 mg/m2) in patients with different solid tumors in advanced disease setting. Legal entity responsible for the study: N/A Funding: Intas Pharmaceuticals Ltd., India Disclosure: All authors have declared no conflicts of interest. 157P Survey of the onset of the dose limiting toxicity in oncology phase I trial: How long should we assess the toxicity profiles in the era of molecular targeted drug development? N. Kobayashi1, N. Yamamoto2 Clinical Research Coordinator Section, Center for Research Administration, National Cancer Center Hospital, Tokyo, Japan, 2Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan 1 Background: The mainstream of the development of anticancer drugs has changed from cytotoxic drugs to molecularly targeted drugs. The development of immunotherapy has also increased since 2009. The dose-limiting toxicity (DLT) in phase I trials is usually evaluated during the first cycle of therapy such as grade 3 nonhematological and grade 4 hematological toxicities. The chronic toxicities after 1st cycle of treatment are often required to be evaluated in the molecular targeted drugs, but the period of DLT evaluation has still been conservative in phase I trials. We explored the favorable assessment period of acute and chronic toxicities of the single-agent molecular targeted drugs in phase I trials. Methods: We retrospectively surveyed the consecutive cases in phase I trials of the single-agent molecularly targeted drugs in our hospital. Results: From August 1996 to December 2014, a total of 780 patients were enrolled in phase I trials of the single-agent molecular targeted drugs. Median age was 66 years (range 25-94). DLT and the toxicities equivalent to DLT were observed in 66 patients. As acute toxicities, 88 grade 3 or more non-hematological, and 10 grade 4 hematological toxicities were observed. As for chronic toxicities, 12 grade 3 or more nonhematological toxicities were observed. However, no grade 4 hematological toxicities were observed as chronic toxicity. Grade 3 or more chronic non-hematological toxicities without acute toxicities were observed in 8 patients. Volume 27 | Supplement 9 | December 2016 158P The inhibitory effects of canstatin on VEGF-A-induced lymphangiogenesis and metastasis in an oral squamous cell carcinoma SCC-VII animal model M.G. Bae, J. Hwang-Bo, J-H. Park, I.S. Chung Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University, Yongin, Republic of Korea Background: A spreading of tumor cells to lymph nodes through a lymphangiogenesis is common and an early event in malignant tumor, especially in metastasis of head and neck squamous cell carcinoma (SCC). The inhibition of tumor-induced lymphangiogenesis is a attractive target for therapeutics designed to restrict the metastatic spread of tumor. We investigated the inhibitory effects of canstatin on oral SCC-induced lymphangiogenesis and metastasis both in vivo and in vitro. Methods: We established an orthotropic oral SCC animal model to investigate the in vivo inhibitory effect of canstatin and analyzed using immunohistochemistry and H&E staining. To examine the inhibitory effect of canstatin on VEGF-A-induced lymphangiognensis, we performed an in vivo Matrigel plug assay. Proliferation, tube formation and migration assay using human lymphatic endothelial cells were also performed. The anti-lymphangiogenic mechanism of canstatin was investigated in lymphatic endothelial cells stimulated by VEGF-A using RT-PCR and western blot analysis. Results: Canstatin treatment decreased final tumor volumes and weights, as well as densities of blood and lymphatic vessels in an orthotropic oral SCC animal model. Lung metastasis of oral SCC was significantly reduced in canstatin-treated animals. Canstatin reduced VEGF-A expression in SCC-VII cells treated with the hypoxia mimetic agent, CoCl2. VEGF-A induced in vivo lymphatic vessel formation in a Matrigel plug, but this was remarkably reduced in a canstatin-treated Matrigel. Canstatin suppressed the expression of vascular endothelial growth factor receptor (VEGFR)-1 and -2 stimulated by VEGF-A. And canstatin significantly reduced the expression of VEGF-A, VEGFR-1, and -2 in SCC-VII-induced tumors. In addition, canstatin suppressed the VEGF-Ainduced phosphorylation of VEGFR-1 and -2. Conclusions: Our results indicate that canstatin exhibits anti-tumoral and antilymphangiogenic activities against oral SCC cells. Anti-lymphangiogenic signaling by canstatin is probably mediated by the suppression of the integrin avb3/VEGFR-1 and/ or -2 signaling induced by VEGF-A. Legal entity responsible for the study: Kyung Hee University Funding: Basic Science Research Program through the National Research Foundation of Korea (NRF), The Ministry of Education, Science and Technology (NRF2013R1A1A2062398) Disclosure: All authors have declared no conflicts of interest. 159P Antioxidant effect of mangiferin: The potential anti-cancer therapeutic agent R. Roy, K. Banerjee, R. Bhattacharya, A. Mukhopadhyay Molecular Biology, Netaji Subhas Chandra Bose Cancer Research Institute, Kolkata, India Background: Mangiferin is the natural xanthone C-glucoside, primarily found in mangifera indica, exhibits promising chemotherapeutic and iron chelating potential which will help to prevent cancer. Previous reports showed that it induces apoptosis by suppressing Bcl-xL in HL-60 cells (1).Other study showed that mangiferin is effective in preventing colon cancer (2). Another study reported its iron chelating capacity and thus causing cell cycle arrest and apoptosis (3). Thus, in this study we have hypothesized that mangiferin can serve as a natural anticancer agent and low dose of mangiferin in combination with chemotherapeutic agent will improve its effectiveness and it will also combat with the drug resistance. Methods: DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging method is used for determining the antioxidant property of extract. The reduction capacity of DPPH radical is determined by the decrease in its absorbance (Kmax) measured at 517 nm which is induced by antioxidants. In vitro DPPH radical scavenging activity was carried out by adopting the method of Liyana-Pathiranam. A solution of 0.135mM DPPH in methanol was prepared and 1.0ml of this solution is mixed with 1.0mlof the extract in methanol containing 0.02-0.5 mg of extract. The reaction mixture was mixed thoroughly and kept in dark at 25 C for 30mins. The absorbance was measured by UV- doi:10.1093/annonc/mdw579 | ix49 abstracts Annals of Oncology Vis Spectrophotometer at 517 nm. Ascorbic acid and BHT were taken as standard antioxidant. Radical scavenging activity is expressed as % inhibition of DPPH radicals. IC50 value calculated. The tests were done in triplicate simultaneously for the extract. % scavenging activity ¼ (1- absorbance of sample/absorbance of control)*100. Results: The IC50 value from DPPH radical scavenging activity of Mangiferin was found to be 290mg/ml with a positive correlation coefficient (R2¼0.879). Conclusions: Mangiferin can serve as a potential anti-cancer agent alone or in combination with chemotherapeutic drug that will reduce the adverse effect of chemotherapeutic agents. Thus, large scale study is needed to use this natural antioxidant & iron chelating pharmacologically active component in practice and modulate the disease like Myelodisplastic Syndrome. Legal entity responsible for the study: N/A Funding: Netaji Subhas Chandra Bose Cancer Research Institute Disclosure: All authors have declared no conflicts of interest. 160P The inhibitory effects of recombinant canstatin and 3oacetyloleanolic acid on angiopoietin-1-induced lymphangiogenesis for effect on cell growth inhibition and apoptosis through cell cycle arrest assay. The compounds were tested for inhibitory activity against PI3Ka and mTOR via kinase inhibition assay. The docking analysis was also carried out with PI3K and mTOR domain to elucidate vital structural residues necessary for bioactivity. Results: The compounds were developed in excellent yield. The cytotoxicity studies suggests that, synthesized derivatives exhibit considerable inhibition with average IC50 for compound 7h were found to be 1.21, 2.03 and 2.86 mmol/l against A549, H157 and H52 cells, respectively. The compound 7h causes a significant increase in the number of cells in G0–G1 phase, with a corresponding decrease in the number of cells in S and G2– M phase. It induces tumor cell apoptosis in a dose-dependent manner. The compound 7h, showed IC50 of 3.2360.23 mM and 1.2160.15 against PI3Ks and mTOR, respectively. Whereas, the docking results showed that compound 7h, 7l, 7m, 7e were found to be the most efficient analogues to inhibit PI3Ks and mTOR by binding the ATP pocket via creating interactions with ASP2195, ASP2357, LYS802 and ASP810. Conclusions: In conclusion, 1,3,5-triazine-thiourea has shown promising antitumor activity via attenuation of PI3K/mTOR against NSCLC and represents potential therapeutic application for further development. Legal entity responsible for the study: SHIATS Funding: SHIATS Disclosure: All authors have declared no conflicts of interest. J. Hwang-Bo, K.O. Jang, M.G. Bae, J-H. Park, I.S. Chung Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University, Yongin, Republic of Korea Background: The spread of tumor cells to lymph nodes commonly occurs in tumors and is an early event in metastasis tumor disease. Angiopoietin-1 is a major angiogenic and lymphangiogenic growth factor in colon carcinoma CT-26 cells at a hypoxic condition. In this study, we investigated the inhibitory effects of recombinant canstatin and 3-O-acetyloleanolic acid (3AOA) on angiopoietin-1-induced lymphangiogenesis both in vitro and in vivo. Methods: To examine the inhibitory effects of recombinant canstatin and 3AOA on angiopoietin-1-induced lymphangiognensis, we performed proliferation, tube formation and migration assay using human lymphatic endothelial cells. The inhibitory effects of recombinant canstatin and 3AOA were further determined in an angiopoietin-1-stimulated in vivo Matrigel plug and a heterotropic CT-26 colon carcinoma animal model. The anti-lymphangiogenic mechanisms of recombinant canstatin and 3AOA were investigated in lymphatic endothelial cells stimulated by angiopoietin-1 using RT-PCR and western blot analysis. Results: Recombinant canstatin or 3AOA inhibited the proliferation, tube formation, and migration of angiopoietin-1-treated human lymphatic endothelial cells. Recombinant canstatin inhibited lymphangiogenesis via suppression of integrindependent FAK signaling induced by angiopoietin-1/Tie-2 and/or VEGFR-3. 3AOA inhibited the activation of signaling factors such as FAK, AKT, and ERK1/2 involved in angiopoietin-1/Tie-2 signaling pathway. Recombinant canstatin and 3AOA reduced the development of new lymphatic vessels in angiopoietin-1-stimulated Matrigel plug. Also recombinant canstatin and 3AOA inhibited the tumor growth and tumor-induced lymphangiogenesis in heterotropic CT-26 colon carcinoma animal model. Conclusions: Our results indicate that recombinant canstatin and 3AOA exhibit antilymphangiogenic effects on angiopoietin-1-induced lymphangiogenesis. Our findings suggest that recombinant canstatin and 3AOA have a potential to inhibit colon carcinoma. Currently, we investigate the combinatory effects of recombinant canstatin and 3AOA. Legal entity responsible for the study: Kyung Hee University Funding: Basic Science Research Program through the National Research Foundation of Korea (NRF), Ministry of Education, Science and Technology (NRF2015R1D1A1A01059824) Disclosure: All authors have declared no conflicts of interest. 161P 162P S. Kaushik1, M. Rikki2, T.R.S. Kumar3, S. Bhatnagar2 Cancer Research Lab 1, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram (Trivandrum), India, 2AIB, Amity University ACB & PDM, Noida, India, 3Cancer Research Lab1, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram (Trivandrum), India 1 Background: Heterocyclic molecules have been exhaustively explored for their pharmacological importance as antitumour agents. Several polyfunctionally substituted heterocycles such as pyrazoles, isoxazole, pyrimidine, thiazol incorporating oxygen and sulphur heterocycles have been explored in this direction. 2-vinylchromones are rare class of oxygen heterocycles. Natural and synthetic analogues of 2- vinyl chromones have been reported to possess antiallergic, antitumor, antiviral, antioxidant and antiinflammatory activity. In the present study synthesis of novel analogues of 2-vinyl chromones was undertaken. Methods: A new class of isoxazolyl chromones 3(a-f) were synthesized and evaluated for their cytotoxic activity against human breast cancer cell lines. Results: Amongst the analogues synthesized compound 3d exhibited potent antiproliferative activity alone and in combination with ER agonist estradiol (E2) and antagonist 4-hydroxytamoxifen in human breast cancer cell line MCF-7 in dose dependent and time dependent manner. Molecular docking studies have been reported to ascertain the binding site of compounds 3(a-f) in ERa and ERb. Furthermore, FACS analysis revealed that MCF-7 Cyt C Scat-3 NLS cells treated with compound 3d triggered cells arrest at the G0/G1 phase of the cell cycle. Hoechst staining results indicated that apoptosis was induced when cells were treated with compound 3d. These findings were further corroborated with the results obtained through fluorescence based FRET probe analysis which indicated that compound 3d induced apoptosis via the activation of caspase-3 pathway. Conclusions: These investigations revealed that isoxazolyl chromones have potential for the development of antitumor drugs towards breast cancer treatment. Legal entity responsible for the study: Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India; Amity University, Noida, India Funding: Indian Council of Medical Research, New Delhi, India Disclosure: All authors have declared no conflicts of interest. Discovery of novel 1,3,5-triazine-thiourea based dual PI3K/ mTOR inhibitor against Non-small cell lung cancer (NSCLC) 1 1 163P An evaluation of the anti-cancerous potential of 5-episinuleptolide in pancreatic cancer 2 U.P. Singh , J.K. Srivastava , H.R. Bhat Department of Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences, Allahabad, India, 2Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, India 1 Background: The phosphatidylinositol 3-kinase (PI3K) signalling pathway plays crucial roles in cell growth, proliferation and survival, and found frequently dysregulated pathway in lung cancer. Consequently, 1,3,5-triazine based inhibitors of key kinases in the pathway, including PI3K, AKT and mTOR, have been extensively pursued in oncology in recent years. The PI3K-Akt-mTOR pathway is commonly deregulated in human malignancy including NSCLC. Therefore, the present study was aimed to develop novel 1,3,5-triazine derivatives as dual PI3K/mTOR for lung carcinoma. Methods: The 1,3,5-triazine compounds were synthesized via multi-component reaction. The compounds were tested for determination of anticancer activity against three human NSCLC cell lines A549, H157 and H52. The compounds were also tested ix50 | abstracts Novel isoxazolyl chromones antagonizing ERa induces anticancer activity via triggering caspase-3 activation Y.H. Kuo1, J-H. Sheu2, W-C. Tsai3 Hemato-oncology, Chi-Mei Medical Center, Tainan, Taiwan, 2Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan, 3Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan 1 Background: Cancer causes the highest level of mortality in Taiwan among the patient population, pancreatic cancer being a large contributor to this circumstance. Even with advancements made in chemotherapeutic and radiation therapies, the likelihood that a patient will survive pancreatic cancer is less than a 1.9 percent. 5-epi-sinuleptolide, the norditerpene extracted from Sinularia sp has shown cytotoxic effects leading to apoptosis and anti-cancerous activity, but the precise mechanisms by which it carries out these phenomena have yet to be deduced. The goal of this research was to investigate and reveal the mechanisms by which 5-epi-sinuleptolide inhibited cell growth, decreased cell viability, caused cell cycle arrest, and ultimately induced pancreatic cancer cell death. Volume 27 | Supplement 9 | December 2016 Annals of Oncology Methods: In our study, two pancreatic cancer cell lines, Panc-1 and BxPC-3 were used, which present Gemzar-resistant and –sensitive respectively. The cell viability was determined by MTT assay. The Annexin V/PI, caspase-3 activity and cell cycle were analyzed by flow cytometry. Transwell invasion assay was applied for invasiveness measurement. The underlining mechanisms regulated by 5-epi-sinuleptolide on pancreatic cancer cells were revealed by western blotting. Results: In this study, the inhibitory effects of cell growth upon 5-epi-sinuleptolide on pancreatic cancer cells were determined. 5-epi-sinuleptolide treatment could induce apoptosis, activation of caspase-3 and cell cycle arrest in pancreatic cancer cells. Besides, the invasion and cell proliferation were inhibited after 24 h treatment of 5-episinuleptolide. The results of western blotting showed that 5-epi-sinuleptolide could surely inhibit STAT3, AKT and ERK phosphorylation and decrease the endogenous protein level through a transcriptional regulation-independent mechanism. Conclusions: In conclusion, the diminution of the phosphorylation parallel with the decrease of the endogenous protein level of STAT3, AKT and ERK might play the role, at least partially, in the anti-pancreatic cancer potential of 5-epi-sinuleptolide. Legal entity responsible for the study: Kuo Yu Hsuan Funding: Chi-Mei Medical Center Research Funding: CMFHR10251 Disclosure: All authors have declared no conflicts of interest. 164TiP Phase I study of LOXO-101, a selective TRK inhibitor, in pediatric patients with cancer T.W. Laetsch1, R. Nagasubramanian2, S.G. Dubois3, L. Mascarenhas4, D. Hawkins5, N. Shukla6, B. Turpin7, S. Smith8, M. Reynolds8, S. Cruickshank8, L. Donahue8, M.C. Cox8, A. Pappo9 1 Pediatrics, University of Texas Southwestern Medical Center/Children’s Health, Dallas, TX, USA, 2Hematology/Oncology, Nemours Children’s Hospital, Orlando, FL, USA, 3Hematology/Oncology, Dana Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, USA, 4Hematology/ Oncology, Childrens Hospital Los Angeles University of Southern California, Los Angeles, CA, USA, 5Hematology/Oncology, Seattle Children’s Hospital, Seattle, WA, USA, 6Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA, 7Hematology/Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA, 8Clinical Development, Loxo Oncology, Inc, South San Francisco, CA, USA, 9Solid Tumor Division, St Jude Children’s Research Hospital, Memphis, TN, USA abstracts differentiation and survival of neurons. Translocations involving the NTRK1/2/3 kinase domain, mutations involving the TRK ligand-binding site, amplifications of NTRK, TRK splice variants, and autocrine/paracrine signaling have been described in diverse tumor types and may contribute to tumorigenesis. A broad range of pediatric malignancies have been found to harbor NTRK fusions, including infantile fibrosarcoma (IFS), congenital mesoblastic nephroma (CMN), secretory breast cancer, pediatric papillary thyroid cancer, pediatric gliomas and Ph-like acute lymphoblastic leukemia. Additionally, TRK protein over-expression is common in neuroblastoma. LOXO-101 is the first small-molecule selective inhibitor of TRKA, -B, and -C in clinical development and has demonstrated tumor inhibition in preclinical models and clinically meaningful responses in patients with TRK fusion cancers in an adult phase 1 trial. Trial design: We have initiated an open-label, multi-center Phase I dose escalation/dose expansion study with LOXO-101 in pediatric patients with solid tumors and primary CNS tumors (NCT02637687). Patients with advanced cancer between the ages of 1 and 21 years are eligible, as well as patients as young as 1-month of age with a primary diagnosis of IFS or CMN and a documented NTRK fusion. Twice-daily oral dosing of LOXO-101 capsules is administered on a continuous 28-day schedule. LOXO-101 is available in an oral liquid formulation for patients unable to swallow capsules. PKdirected intra-subject dose escalation is permitted, with target exposures equivalent to the recommended Phase 2 dose in adults of 100 mg BID. Dose escalation utilizes a Rolling 6 design. The objective of the study is to determine the maximum tolerated dose and initial evidence of the efficacy of LOXO-101 in different tumor types. Eligibility for the dose expansion cohorts will require patient tumor samples to have documented alterations of an NTRK gene or TRK protein. Molecular abnormalities will be characterized through the analysis of archival tissue. Enrollment began in December 2015 and is ongoing. Clinical trial indentification: NCT02637687 Legal entity responsible for the study: Loxo Oncology, Inc. Funding: Loxo Oncology, Inc. Disclosure: S. Smith, M. Reynolds, S. Cruickshank: Consultant fees paid by Loxo Oncology, Inc. L. Donahue: Employee and stockholder of Loxo Oncology, Inc. M.C. Cox: Employee and stock hold of Loxo Oncology, Inc. All other authors have declared no conflicts of interest. Background: Neurotrophin ligands and their receptors TRKA, TRKB, and TRKC (encoded by NTRK1, NTRK2, and NTRK3) are important for growth regulation, Volume 27 | Supplement 9 | December 2016 doi:10.1093/annonc/mdw579 | ix51 Annals of Oncology 27 (Supplement 9): ix52, 2016 doi:10.1093/annonc/mdw580 Endocrine tumours 165P Standardized incidence and associated factors for thyroid cancer in diabetic patients: a population-based analysis C.K.H. Wong1, B.H. Lang2, F-F. Jiao1, C.L. Lam1 Dept. of Family Medicine & Primary Care, The University of Hong Kong, Hong Kong, China, 2Department of Surgery, Queen Mary Hospital University of Hong Kong, Hong Kong, China abstracts 1 Background: Although recent studies have suggested that the rise in thyroid carcinoma (TC) might be linked to the rising incidence of diabetes mellitus (DM), larger epidemiological evidence and proposed mechanism are lacking. Our study aimed to examine the standardized-incidence and associated factors of TC, after taking into account of DM control and therapy, in a large DM cohort. Methods: Using a prospectively-collected population database, 144,084 diabetic patients managed in primary care without history of TC were identified. The time atrisk of TC was calculated from the date of cohort entry to the date of TC, date of death or last follow-up, whichever came first. The TC incidence in this cohort was then compared to that of the general population using the standardized incidence ratio (SIR) after stratifying by age (19, 20-44, 45-64 and 65 years old) and sex. To examine the association between clinical factors (socio-demographics, BMI, average HbA1c level over time, duration of DM and type of anti-DM medications) and incidence of TC, the Cox proportional hazards regression model was used for univariate and multivariate analyses. Results: After a 323,844 person-years of observation, 36 new TCs were diagnosed. Compared to the general population, the TC incidence in the cohort was not significantly increased regardless of age and sex. For males, the overall SIR was 0.665 (0.095-1.234) while for females, it was 0.905 (0.562-1.248). In the univariate analysis, females (p ¼ 0.003), lower education level (p ¼ 0.043) and more frequent primary care DM visits (p < 0.001) were significant associated factors. After adjusting for education level, females (HR ¼ 4.50,95%CI¼1.75-11.63, p ¼ 0.002) and more frequent primary care DM visits (HR ¼ 1.13,95%CI¼1.101-1.160, p < 0.001) were independent associated factors for TC. Conclusions: Contrary to recent evidence, diabetic patients managed in primary care were not at greater risk of developing TC relative to the non-diabetic normal population. Females and more frequent primary care DM visits were independent associated factors for TC. The latter finding implies increase detection/surveillance during unrelated primary care visit might be responsible for the recent surge of TC in diabetic patients. Legal entity responsible for the study: N/A Funding: Food and Health Bureau, Hong Kong SAR government Disclosure: All authors have declared no conflicts of interest. 166P Extent of neck dissection in locally advanced thyroid cancers 1 R. Vaish , A. Mahajan2, S. Shah1, S. Sharma1, D. Chaukar1, S. Thiagarajan1, A. D’Cruz1 1 Head and Neck Surgical Oncology, Tata Memorial Hospital Centre, Mumbai, India, 2Radiodiagnosis, Tata Memorial Hospital Centre, Mumbai, India Background: Thyroid cancer has an indolent course with low mortality. The extent of neck dissection is a contentious issue. Clearance of level IIB and V is associated with larger incision with clearance around spinal accessory nerve resulting in cosmetic and functional morbidity. Methods: 544 thyroidectomies were performed for locally advanced thyroid cancer. Level wise node sampling with histopathology details were available for 92 patients with 160 lateral neck dissections which were analysed further. The incidence of level IIB and V metastasis and factors predicting were analysed. Demographic and Histopathologic details were entered in SPSS version 20 and descriptive analysis was used to calculate the frequency. Univariate analysis was performed using chi square test and multivariate analysis was performed using binary logistic regression. Results: Ninety-two patients underwent thyroidectomy with neck dissection 55 papillary, 23 variant of papillary, 7 medullary and 7 for poorly/anaplastic thyroid carcinoma. Seventy three T3 and 19 were T4 thyroid carcinoma. Level IIB was cleared in 142 and level V in 74 neck dissections. Level V was cleared only when level II through IV sampling showed metastatic node on frozen section. Level IIb was positive in 7% (10/ 142) and level V in 18.9% (14/74) of cases. Two of 10 level IIB were the isolated level of metastases. On univariate analysis the factors predicting level IIB metastasis were T stage, level IIA, III and IV metastasis while for level V metastasis were presence of lymphovascular emboli (LVE), level IV and VI metastasis. On multivariate analysis independent predictor for level IIB metastasis were T stage, level IV metastasis and LVE while for level V metastasis were level IV metastasis. Conclusions: Incidence of IIB metastasis is low and should be addressed in T4 thyroid cancer with level IV metastasis. However, high incidence of level V metastasis warrants level V clearance in lateral compartment positive neck. Legal entity responsible for the study: Tata Memorial Hospital Funding: N/A Disclosure: All authors have declared no conflicts of interest. 167P Predictive factors for central neck lymph node metastasis in patients with papillary thyroid microcarcinoma without suspicious metastasis by preoperative ultrasonography H. Oh1, Y.S. Kim2 1 Radiology, Chosun University College of Medicine, Gwangju, Republic of Korea, 2Surgery, Chosun University College of Medicine, Gwnagju, Republic of Korea Background: Papillary microcarcinoma (PTMC) is a small papillary thyroid carcinoma measuring 1cm or less in diameter. Recently, incidence of PTMC has been increased due to an increase in the detection of subclinical disease such as small and low-risk carcinomas with ultrasonography and fine needle aspiration cytology. However, there is central neck lymph node metastasis in patients with PTMC without clinical evidence of metastasis by preoperative ultrasonography. We performed analysis to determine the influencing factors for central lymph node metastasis in PTMC although there was no clinical evidence of metastasis by preoperative ultrasonography. Methods: We analyzed retrospectively 625 patients with PTMC underwent thyroid surgery at Chosun University Hospital from January 2002 to December 2012. Finally, we included 575 patients who had no evidence of lymph node metastasis by preoperative ultrasonography. We reviewed medical records including clinical information and pathologic report. Results: Central lymph node metastasis was found in 81 patients (14.1%) among total 575 patients. A lymph node metastasis occurred frequently according to univariate analysis in patients with following factors; more than 0.5cm in largest tumor size by preoperative sonography and pathologic reports (p ¼ 0.048 and p ¼ 0.001, respectively) and lymphovascular invasion (p < 0.001). Multivariate analysis revealed that the gender (Female vs Male), pathologic tumor size (0.5 1cm vs < 0.5cm) and lymphovascular invasion (Yes vs No) were significant associated factors for lymph node metastasis [Odds ratio (OR)¼0.498, 95% confidence interval (CI)¼0.250–0.992, P ¼ 0.047; OR ¼ 2.450, 95% CI ¼ 1.313–4.570, P ¼ 0.005; and OR ¼ 24.954, 95% CI ¼ 2.430– 256.217, P ¼ 0.007, respectively]. Conclusions: Male gender, larger tumor size (0.5cm) and lymphovascularinvasion were found as the risk factors for central neck lymph node metastasis in patients with PTMC without suspicious clinical evidence of node metastasis. We concluded that prophylactic central neck lymph node dissection might be required in these cases of PTMC. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. Annals of Oncology 27 (Supplement 9): ix53–ix67, 2016 doi:10.1093/annonc/mdw581 168O Right-sided versus left-sided primary tumor location in patients with KRASmut metastatic colorectal cancer (mCRC) treated with 1st-line anti-VEGF plus chemotherapy (CTx) - Data from the National Czech Registry 2, K. Hejduk3, L. Zdrazilova-Dubska4, M. Voc ka5, R. Obermannova1, L. Ostrızkova R. Vyzula1, B. Bencsikova1, L. Petruzelka5 1 Clinic of Comprehensive Cancer Care and Regional Center for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic, 2 Clinic of Internal Medicine – Hematology and Oncology, Masaryk University Hospital Brno FN Brno Bohunice, Brno, Czech Republic, 3Masaryk University, Institute of Biostatistics and Analysis, Brno, Czech Republic, 4Department of Laboratory Medicine, Masaryk Memorial Cancer Institute, Brno, Czech Republic, 5Department of Clinical Oncology, General Teaching Hospital and The First Faculty of Medicine of Charles University in Prague, Prague, Czech Republic Background: CTx plus bevacizumab (bev) is a 1st-line standard for patients (pts) with mCRC. While location of the primary tumor was found to be prognostic in pts with KRASwt mCRC, especially when treated with anti-EGFR plus 1st-line CTx, the prognostic role is unknown for pts with KRASmut mCRC treated with anti-VEGFcontaining CTx. Methods: Data from 3 national comprehensive cancer centers in Czech Republic were collected prospectively from 01/2009 - 09/2015. A retrospective analysis of outcomes of 1047 pts with mCRC was performed. All pts were treated with 1st-line bev plus FOLFOX, CapOx or FOLFIRI, irrespective of the KRAS status (all-RAS since 2015). The primary objective was assessment of OS (right vs left-sided) in KRASmut mCRC. OS and PFS were calculated using the Kaplan-Meier method, Cox proportional hazards model was used to evaluate the effect of all potential prognostic factors on the survival measures. Results: Right-sided location of the primary tumor was in 281 of 1047 pts (26.8%), leftsided in 430 (41.1%) and rectal in 336 (32.1%). KRAS status was known in 930 pts (88.8%): 44.3% KRASwt and 44.5% KRASmut. Statistically significant differences were observed in KRAS status in right- vs left-sided mCRC vs. rectum (Fisher-exact p ¼ 0.006). OS and PFS achieved longer time periods when compared in left- vs. rightsided mCRC. In pts with KRASmut status, OS was 19.9 mon (95% CI 15.4–24.5) in right-sided vs 25.0mon (95% CI 21.9–28.2) in left-sided mCRC; HR: 1.19 (95% CI 0.90– 1.58; Wald test p ¼ 0.231) and 23.7 mon (95% CI 19.7–27.7) in rectal cancer. Likewise, PFS was 9.6 mon (95% CI: 7.8–11.4) vs. 10.5 mon (95% CI: 9.1–11.9), HR:1.06 (95% CI 0.83–1.36, p ¼ 0.653) in right- vs left-sided mCRC and in rectal cancer 9.9 mon, HR: 1.01 (95% CI 0.79–1.06, p ¼ 0.934). Conclusions: Although right–sided primary tumor location is a well recognized negative prognostic factor in mCRC this significance was lost when analyzing only the KRASmut subgroup of patients. Legal entity responsible for the study: N/A Funding: Masaryk Memorial Cancer Institute Disclosure: All authors have declared no conflicts of interest. 170O Lymph node status as a prognostic factor after palliative resection of metastatic colorectal cancer Q. Li1, S. Cai2 Department of Colorectal Cancer, Shanghai Cancer Center Fudan University, Shanghai, China, 2Colorectal surgery, Shanghai Cancer Center Fudan University, Shanghai, China 1 Survival rate was generated using Kaplan-Meier curves, and the differences were compared with the log-rank test. A Cox proportional hazards regression model was then built to evaluate the risks of variables on CSS in colorectal cancer patients. The results were validated in additional 392 patients from Fudan University Shanghai Cancer Center (FUSCC). Results: A total of 17,553 patients with CRC were identified in SEER database. X-tile program identified 2 and 10 as optimal cutoff values to divide patients into high, middle and low risk. N stage and negative lymph node counts were validated as independent prognostic factors in both univariate and multivariate analyses, and even in subgroup analysis of each N stage (P < 0.05). Patients in FUSCC demonstrated that tumor burden (P ¼ 0.042), negative lymph node count (P ¼ 0.039), and sequential chemotherapy (P ¼ 0.040) were significant predictors of poorer CSS. Specifically, the prognosis of N0 patients was significantly more favorable than that of N2 patients (P ¼ 0.038), although there was no significant difference between N0 and N1 patients (P ¼ 0. 112). Conclusions: Primary tumor lymph node status was a strong predictor of CSS after palliative resection of metastatic colorectal cancer. Advanced N stage and small NLN count were high risk of cancer related death after palliative resection of primary tumor.Standard LN dissection may still necessary for palliative resection of metastatic colorectal cancer. Legal entity responsible for the study: Qingguo Li Funding: N/A Disclosure: All authors have declared no conflicts of interest. 171O Development of nomogram for predicting lymph node metastases in submucosal colorectal cancer S. Fujino1, N. Miyoshi2, M. Ohue2, M. Yasui2, Y. Fujiwara2, M. Yano2, M. Higashiyama2, M. Sakon2 1 Gastroenterological Surgery, Osaka University, Osaka, Japan, 2Surgery, Osaka Medical Center for Cancer and Cardiovascular Dideases, Osaka, Japan Background: In colorectal cancer (CRC), the possibility of lymph node (LN) metastases is important to select the treatment. According to the Japanese Society for Cancer of the Colon and Rectum guidelines for the treatment of colorectal cancer (JSCCR Guidelines), the surgical resection with LN dissection is generally recommended for submucosal (SM) CRC. However, some SM CRC without the risk factors relating to LN metastases are treated only endoscopically. The probability of LN metastasis is about 10% in SM CRC, and we developed a nomogram to predict LN metastases more accurately in each patient. Methods: 509 patients with SM CRC were retrospectively investigated from 1984 to 2008. All patients underwent curative surgical resection at the Osaka Medical Center for Cancer and Cardiovascular Diseases. 113 patients with inadequate pathological data were excluded. 293 patients who underwent surgery from 1984 to 2008 were included in the training-set (TS), and a logistic regression model was used to develop the prediction model for LN metastases. 103 patients who underwent surgery from 2009 to 2012 were included in the validation-set (VS), and the developed prediction model was validated. Results: Univariate analysis of pathological factors showed that tumor invasion depth (0.098), positive lymphatic invasion (P < 0.001), positive vascular invasion (P ¼ 0.036), and low histologic grade (muc, por, sig) (P < 0.001) were significantly corrected using a logistic regression model with the area under the curve (AUC) of 0.717. The prediction model was validated by VS and the AUC was 0.920. Conclusions: We evaluated the risk factors of lymph node metastases in SM CRC, and made a novel nomogram for predicting LN metastases. Our nomogram can help to decide the additional surgical treatment after endoscopic resection for each patient. This prediction model may help clinicians to decide the personalized treatment following endoscopic resection. Legal entity responsible for the study: Osaka Medical Center for Cancer and Cardiovascular Diseases Ethics Committee Funding: Osaka Medical Center for Cancer and Cardiovascular Diseases Disclosure: All authors have declared no conflicts of interest. Background: Lymph node (LN) status is one of the most important predictors for M0 colorectal cancer patients. However, its clinical impact on stage IV colorectal cancer remains unclear. The aim of this study was to explore the prognostic value of lymph node status after palliative resection of primary colorectal tumor. Lymph node (LN) status is one of the most important predictors for M0 colorectal cancer patients. However, its clinical impact on stage IV colorectal cancer remains unclear. The aim of this study was to explore the prognostic value of lymph node status after palliative resection of primary colorectal tumor. Methods: Surveillance, Epidemiology and End Results (SEER)-registered metastatic colorectal cancer patients diagnosed between 2004 and 2010 were included in this study. C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts Gastrointestinal tumours, colorectal abstracts 172PD Final analysis: Phase II trial of irinotecan/S-1/cetuximab (IRIS/Cet) as second line treatment in patients with KRAS exon2 wild type metastatic colorectal cancer: HGCSG0902. Comparison of administration interval in cetuximab treatment T. Ando1, S. Yuki2, H. Nakatsumi3, T. Muranaka3, A. Hosokawa1, Y. Tsuji4, M. Nakamura5, O. Muto6, T. Sasaki7, I. Iwanaga8, K. Hatanaka9, A. Sato10, K. Eto11, K. Furukawa12, M. Tateyama13, Y. Takahashi14, S. Sogabe15, T. Honda16, Y. Sakata17, Y. Komatsu3 1 Gastroenterology and Hematology, Faculty of medicine, University of Toyama, Toyama, Japan, 2Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan, 3Cancer Center, Hokkaido University Hospital, Sapporo, Japan, 4Medical Oncology, KKR Tonan Hospital, Sapporo, Japan, 5 Gastroenterology, Sapporo City General Hospital, Sapporo, Japan, 6Medical Oncology, Japanese Red Cross Akita Hospital, Akita, Japan, 7Internal Medicine, Hokkaido Gastroenterology Hospital, Sapporo, Japan, 8Medical Oncology, Japanese Red Cross Kitami Hospital, Kitami, Japan, 9Gastroenterology, Hakodate Municipal Hospital, Hakodate, Japan, 10Medical Oncology, Hirosaki University Hospital, Hirosaki, Japan, 11Gastroenterology, Tomakomai City Hospital, Tomakomai, Japan, 12Gastroenterology, Niigata City General Hospital, Niigata, Japan, 13Internal Medicine, Tomakomai Nisshou Hospital, Tomakomai, Japan, 14Gastroenterology, Hokkaido Cancer Center, Sapporo, Japan, 15 Medical Oncology, Kushiro Rosai Hospital, Kushiro, Japan, 16 Gastroenterology and Hepatology, Nagaski University Hospital, Nagasaki, Japan, 17Misawa City Hospital, Misawa, Japan Background: HGCSG0902 is the multicenter phase II study to investigate the safety and efficacy of irinotecan, S-1 (IRIS) plus cetuximab as second line treatment in patients with KRAS exon2 wild type mCRC. Response rate (RR) was 33.3% (95%CI 20.8-45.9%), therefore primary endpoint was met (Muto O, et al. ESMO 2014). Here we report an exploratory analysis of outcomes based on administration interval of cetuximab (every week [EW] vs bi-weekly [BW]). Methods: Eligibility includes histologically confirmed mCRC, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS exon2 wild type. Patients received S-1 80-120 mg/day p.o. on days 1-14 and irinotecan 100mg/m2 on day 1 and 15 repeated every 28 days. Cetuximab was administrated 400mg/m2 as loading dose and continued 250mg/m2 every week or 500mg/m2 bi-weekly. The primary endpoint was RR and the secondary endpoints were disease control rate, PFS, OS and safety. To compare with EW and BW, Fisher’s exact test was used in terms of patient characteristics, AE, RR, and Log-rank test was used in terms of PFS and OS. Results: Between Mar 2010 and Sep 2013, 58 pts were enrolled. One patient was not administered (57 pts were safety analysis set), and 3 pts were ineligible (54 pts were efficacy analysis set). Based on each physician’s choice, 34 patients of EW and 23 of BW were included in the full safety analysis set. RR was 34.4% in the EW and 31.8% in the BW (p ¼ 1.000). Median PFS was 4.2 months in the EW and 6.1 months in the BW (HR 0.752, p ¼ 0.350). Median OS was 8.9 months in the EW and 10.7 months in the BW (HR 0.902, p ¼ 0.737). The most common non-hematological adverse events of grade 3 or higher were diarrhea (23.5% in the EW vs 52.2% in the BW: p ¼ 0.005) and stomatitis (2.9% in the EW vs 30.4% in the BW group: p ¼ 0.046), these were significantly more common in the BW. Conclusions: IRIS/Cet appeared to be highly effective with RR, PFS and OS in the both treatment schedule. Diarrhea and stomatitis were significantly more common in the BW. Therefore, in case of treatment with IRIS/Cet should be administered in the EW. Legal entity responsible for the study: Nonprofit Organization: Hokkaido Gastrointestinal Cancer Study Group Funding: Nonprofit Organization: Hokkaido Gastrointestinal Cancer Study Group Disclosure: S. Yuki: Honoraria: Taiho Pharmaceutical, Merck Serono, Bristol-Myers Squibb, Takeda Pharmaceutical, Chugai Pharmaceutical, Bayer Yakuhin, Eli Lilly Japan. Y. Tsuji: Y.TSUJI has received honoraria from Merck Serono, Eli Lilly Japan, Chugai, Taiho, Ono, Takeda, Daiichi Sankyo, Kyowa Kirin, Yakult, Nippon Kayaku and Medicon, outside the submitted work. Y. Sakata: Honoraria: Taiho Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Merck Serono, Ono Pharmaceutical, Nikkei Business Publications. Y. Komatsu: Honoraria and/or Research fund: Taiho Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, Merck Serono, Pfizer Japan, Ono Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Eli Lilly Japan, Novartis Pharma, Kureha Corporation. All other authors have declared no conflicts of interest. 173PD MicroRNA MIR21, T cells, and PTGS2 expression in Colorectal Cancer K. Mima1, R. Nishihara2, Z.R. Qian2, H. Baba1, S. Ogino3 Deapartment of gastroenterological surgery, Kumamoto University, Kumamoto, Japan, 2Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, 3Division of MPE Molecular Pathological Epidemiology, Brigham and Women’s Hospital, Boston, MA, USA 1 Background: Prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase-2) produces inflammatory mediator prostaglandin E2 (PGE2), and contributes to suppresses ix54 | abstracts Annals of Oncology antitumor T-cell–mediated immunity. PTGS2-driven inflammatory responses can induce tumor expression of microRNA MIR21 (miR-21) that can increase local PGE2 level by downregulating PGE2-metabolizing enzymes. Thus, we hypothesized that the prognostic association of tumor MIR21 expression level in colorectal carcinoma might depend on PTGS2 expression and that tumor MIR21 expression might be inversely associated with Tcell density in colorectal carcinoma tissue. Methods: Utilizing 765 rectal and colon cancer specimens in the Nurses’ Health Study and the Health Professionals Follow-up Study, we measured MIR21 expression by quantitative reverse-transcription PCR, and PTGS2 expression by immunohistochemistry. Densities of CD3þ, CD8þ, CD45RO (PTPRC)þ and FOXP3þ cells in tumor tissue were determined by tissue microarray immunohistochemistry and computer-assisted image analysis. Multivariable analyses were conducted to assess the statistical interaction between MIR21 and PTGS2 in colorectal cancer-specific survival analysis and the association of MIR21 expression with T-cell density, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, and KRAS, BRAF, and PIK3CA mutations. Results: The association between MIR21 expression and colorectal cancer-specific mortality was statistically significant in PTGS2-high cancers (multivariable hazard ratio of the highest vs. lowest quartile of MIR21, 2.28; 95% confidence interval, 1.42 to 3.67; Ptrend ¼ 0.0004) but not in PTGS2-absent/low cancers (Ptrend ¼ 0.22; Pinteraction ¼ 0.0004). Tumor MIR21 expression was inversely associated with densities of CD3þ and CD45ROþ cells (Ptrend < 0.0005). Conclusions: Our data support a possible role of tumor epigenetic deregulation by noncoding RNA in suppressing antitumor T-cell–mediated immune response, and suggest MIR21 as a potential target for immunotherapy and treatment in colorectal cancer. Legal entity responsible for the study: USA National Institutes of Health (NIH) Funding: USA National Institutes of Health (NIH) Disclosure: All authors have declared no conflicts of interest. 174PD A randomized phase III trial of capecitabine with or without irinotecan driven by UGT1A1 in neoadjuvant chemoradiation of locally advanced rectal cancer (CinClare) T. Zhang1, J. Zhu2, J.Y. Chen3, Y. Zhu4, J. Zhou5, Y. Zhu6, J.H. Jia7, C. Zhang8, X. Wang9, Y.H. Gao10, G. Cai11, B. Luo12, J. Wu13, A. Liu14, B. Xu15, Z. Zhang2 1 Department of Oncology, 1st Affiliated Hospital of Chongqing Medical University, Chongqing, China, 2Department of Radiation Oncology, Shanghai Cancer Center Fudan University, Shanghai, China, 3Department of Oncology, Jiangsu Provincial People’s Hospital (The First Affiliated Hospital of Nanjing Medical University), Nanjing, China, 4Department of Oncology, 2nd Affiliated Hospital Suzhou (Soochow) University, Suzhou, China, 5Department of Oncology, 1st Affiliated Hospital of Suzhou (Soochow) University, Suzhou, China, 6Department of Oncology, Zhejiang Cancer Hospital, Hangzhou, China, 7 Department of Oncology, Liaoning Cancer Hospital & Institute, Shenyang, China, 8Department of Radiation Oncology, Ningbo No.2 Hospital, Ningbo, China, 9Department of Radiation Oncology, West China Hospital, Huaxi, Sichuan University, Chengdu, China, 10Department of Radiation Oncology, Cancer Centre Sun Yat-sen University, Guangzhou, China, 11Department of Radiation Oncology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University, College of Medicine, Shanghai, China, 12Department of Radiation Oncology, Hubei Province Tumor Hospital, Wuhan, China, 13Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fuzhou, China, 14Department of Radiation Oncology, 2nd Affiliated Hospital of Nanchang University, Nanchang, China, 15Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China Background: Early small sample size trials have assessed the addition of irinotecan to standard neoadjuvant CRT in rectal cancer. All patients in case group in ARISTOTLE trial were prescribed with weekly irinotecan dose of 60mg/m2 for four times. In our previous phase I trial, the weekly dose of irinotecan was escalated to 65mg/m2 and 80mg/m2 guided by UGT1A1*28 genetypes in neoadjuvant CRT. Therefore, this phase III trial was designed to confirm the potential improvement in outcomes seen with the addition of irinotecan to CRT. Methods: Patients are randomly allocated to either RT 50 Gy with concurrent capecitabine, followed by a cycle of XELOX two weeks after the end of CRT (Control arm) or RT 50 Gy with concurrent capecitabine and irinotecan, followed by a cycle of capecitabine and irinotecan (Case arm). Capecitabine is prescribed with 825mg/m2 twice daily from first day of RT and given 5 days per week during RT in control group. In the other group, capecitabine dose is 625mg/m2 twice daily and additional weekly irinotecan dose is 80mg/m2 or 65mg/m2 guided by UGT1A1*28 genetypes . Surgery is schedule 8 weeks after the end of CRT, then, five cycles of XELOX are recommended during the course of adjuvant chemotherapy. The primary end point is ypCR. The hypothesis is to increase ypCR from 12% in the control group to 25% in the case group. To detect such a difference, with alpha¼0.05 (two-tailed) and belta¼0.15, 360 randomly assigned patients are required. Secondary end points are toxicities, surgical complications, local control, progression-free survival and overall survival. Results: A total of 121 patients participated in this study from November 2015 to July 2016. The cases were divided into A group(60) and B group (61) randomly. At the analysis time, 25 patients in each group were underwent surgery. The number of cases Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology got pCR was 5(20%) and 12(48%), respectively. Toxic effects and treatment compliance datas have been collected. Conclusions: It is estimated that the study will be completed in September 2017.The tolerability and higher efficacy of the therapy in patients with local advanced rectal cancer treated by neoadjuvant CRT combining with the irinotecan will be evaluated. Clinical trial indentification: NCT02605265, released on December 24, 2015 Legal entity responsible for the study: T. Zhang Funding: Fudan University Shanghai Cancer Center, Disclosure: All authors have declared no conflicts of interest. 169P First-line FOLFOX-4 6 cetuximab in patients with RAS wildtype metastatic colorectal cancer: The open-label, randomized, phase 3 TAILOR trial S. Qin1, J. Xu2, L. Wang3, Y. Cheng4, T. Liu5, J. Chen6, J. Liu7, J. Li8 Department of Oncology, Nanjing Bayi Hospital, Nanjing, China, 2Department of Oncology, 307 Hospital of PLA, Beijing, China, 3Department of Oncology, Shanghai’s First People’s Hospital, No. 85, Shanghai, China, 4Department of Oncology, Jilin Cancer Hospital, Changchun, China, 5Department of Oncology, Zhongshan Hospital affiliated to Fudan University, Shanghai, China, 6Global Clinical Development, Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd, Shanghai, China, 7BioStatistics, Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd, Shanghai, China, 8Department of Oncology, Tongji University Shanghai East Hospital, Shanghai, China 1 Background: Cetuximab in combination with chemotherapy (FOLFIRI or FOLFOX) is a standard-of-care first-line treatment for patients (pts) with RAS wild-type (wt) metastatic colorectal cancer (mCRC). However, there have been questions about the combination with FOLFOX as a standard-of-care first-line treatment for pts with KRAS wt mCRC due to limited available data. The purpose of the randomized, phase 3 TAILOR trial is to confirm the efficacy and safety of FOLFOX-4 þ cetuximab vs FOLFOX-4 in the first-line treatment of pts from China with RAS wt mCRC. Methods: TAILOR (EMR62202-057; NCT01228734) is an open-label, randomized, multicenter, phase 3 trial that includes a modified intention-to-treat (mITT) population of 393 pts from China with RAS wt mCRC treated with FOLFOX-4 6 cetuximab. The primary endpoint of TAILOR is progression-free survival (PFS) time as assessed by an independent review committee (IRC) according to RECIST 1.0; key secondary endpoints include overall survival (OS) time, overall response rate (ORR), and safety/ tolerability. Results: In the mITT population, 193 pts with RAS wt mCRC were randomized to FOLFOX-4 þ cetuximab and 200 pts to FOLFOX-4. Baseline characteristics were reasonably balanced between the 2 treatment arms. Adding cetuximab to FOLFOX-4 significantly improved the primary endpoint of PFS by IRC, with an HR [95% CI] of 0.69 [0.54-0.89] (p ¼ .004; median PFS time, 9.2 vs 7.4 months). The key secondary endpoints of ORR (61.1% vs 39.5%; odds ratio [95% CI] ¼ 2.41 [1.61-3.61]; p < .001) and current assessment of OS (HR [95% CI] ¼ 0.76 [0.61-0.96]; p ¼ .020; median OS time, 20.7 vs 17.8 months) also confirmed clinical benefit from the addition of cetuximab to FOLFOX-4. There were no new or unexpected safety findings. Conclusions: The addition of cetuximab to first-line FOLFOX chemotherapy statistically significantly improved PFS, OS, and ORR in pts from China with RAS wt mCRC, an observation that is consistent with previous pivotal studies. The TAILOR study met its primary objective and confirms cetuximab in combination with chemotherapy as a standard-of-care first-line treatment regimen for pts with RAS wt mCRC. Clinical trial indentification: NCT01228734 EMR62202-057 Legal entity responsible for the study: Merck KGaA, Darmstadt, Germany Funding: Merck KGaA, Darmstadt, Germany Disclosure: J. Chen, J. Liu: Employee of Merck Serono Co., Ltd., Beijing, China. J. Li: Received research funding from Merck and Roche. All other authors have declared no conflicts of interest. 175P CEA clearance pattern is a strong predictor of pathologic complete response after neoadjuvant chemoradiation for rectal cancer: validation of FOWARC trial H. Hu1, J. Huang2, J. Zhang1, Y. Cai1, P. Lan3, J. Wang3, Y. Deng1 Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, 2Department of Medical Oncology, Xiangya Hospital of Central South University, Changsha, China, 3Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 1 (pCR). Predicting pCR can have a significant effect on patients in terms of helping confer prognosis, possibly enabling organ preservation, and potentially avoiding unnecessary surgery. The aim of this study was to investigate the predictive value of carcinoembryonic antigen (CEA) clearance pattern for the tumor response to neoadjuvant CRT in rectal cancer patients with elevated CEA levels (>5ng/ml). Methods: Training set (TS) was based on a retrospective study of 75 rectal cancer patients undergoing neoadjuvant CRT and TME resection between 2012 and 2015. 71 of 495 patients with elevated CEA in FOWARC trial, who were randomly assigned to receive neoadjuvant CRT group were included in validation set (VS). Serum CEA were measured at four (TS) or six (VS) different time points, including base line, and the 2, 4, 6, 8 and 14 weeks during neoadjuvant CRT. An exponential trend line was drawn using the CEA values. Patients were categorized into two groups based on R2 values calculated through trend line, which indicates the correlation coefficient between exponential graph and measured CEA values: exponential decrease group (0.9<R2⬉1.0), and nonexponential decrease group (R2⬉0.9). Results: CEA decrease with exponential pattern was a significant independent predictor for TRG (0-1) (TS: OR ¼ 4.34, CI 1.40 - 13.48; VS: OR ¼ 3.04, CI 1.10 - 8.43), good down-staging (ypTNM stage 0-I) (TS: OR ¼ 4.70, CI 1.53 - 14.43; VS: OR ¼ 7.26, CI 1.79 - 29.37) and pCR (TS: OR ¼ 6.61, CI 1.01 - 40.54; VS: OR ¼ 10.15, CI 1.50 - 68.62). The AUC (Area Under roc Curve) for pCR in TS and VS were 0.685 and 0.726, respectively, which was the strongest factor among clinicopathologic indexes. Conclusions: The pattern of CEA clearance, a simple clinical parameter, normally available in everyday practice, was a independent predictor of pCR for rectal cancer patients. These results would be beneficial to guide individualized treatment strategies for this patients with elevated CEA levels, who were associated with poorer outcome. Clinical trial indentification: NCT01211210 Legal entity responsible for the study: Huabin Hu Funding: Guangzhou Science Funding Disclosure: All authors have declared no conflicts of interest. 176P Robotic anterior resection of rectal cancer without abdominal incision: transanal rectal eversion and resection for specimen extraction: A preliminary and feasibility study D. Zhu, Z. Niu, Y. Wei, J. Xu Department of Colorectal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China Background: The combination of robotic surgery and natural orifice specimen extraction (NOSE) for rectal cancer is scarcely investigated. The aim of this study was to indentify the benefits of robotic resection using a novel approach: transanal rectal eversion and resection for specimen extraction (Robotic TRERSE). Methods: There were totally 26 patients who underwent Robotic TRERSE between Oct. 2013 and June. 2016 at Zhongshan Hospital, Fudan University. The distal rectum coupled with the lesion was everted out of the anus, and the tumor was resected with a sufficient margin above the dentate line under direct sight. Inclusion criteria includes tumor size (5cm), localization (10cm from anal), the lumen ( 2/3 circle), BMI (<30 kg/m2), and cTNM stage (T1-3N0M0). Clinicopathological characteristics and perioperative outcomes were recorded retrospectively. Results: There was no conversion. The maximum diameter of rectal lesions was 2.861.1cm, and distance of the lower edge from the anal verge was 7.762.2 cm. The operating time was 176.4649.5 min, and blood loss was 101.1643.1 ml. Moreover, there were 13.766.4 lymph nodes dissected, and length of distal margin was 2.160.8cm. Postoperative first flatus and resumed liquid diet was 2.160.6 days and 6.560.9 days. Postoperative hospital stay was about 8.764.4 days, while 3 patients developed anastomotic leakage, and managed with conservative treatment. During short-term follow-up period, there is no abdominal infection, pelvic abscess and other severe infectious complication for bacteriological outcome. For functional outcome, no dysuria, sexual function disorder and fecal incontinence were found. Importantly, none were observed local or distant metastasis, and no cancer-related death. Conclusions: Robotic anterior resection of rectal cancer without abdominal incision, using transanal rectal eversion and resection for specimen retrieval, is safe and feasible. This technique requires no traditional abdominal incision with minimal invasiveness and excellent cosmetic effect, and long-term outcome of this surgery needs further investigation. Legal entity responsible for the study: Department of Colorectal Surgery, Zhongshan Hospital, Fudan University Funding: Zhongshan Hospital, Fudan University Disclosure: All authors have declared no conflicts of interest. Background: Approximately 10% to 30% locally advanced rectal cancer patients receiving neoadjuvant chemoradiation (CRT) will have a pathologic complete response Volume 27 | Supplement 9 | December 2016 doi:10.1093/annonc/mdw581 | ix55 abstracts Annals of Oncology 179P 177P New staging system for colorectal cancer patients with synchronous peritoneal metastasis in accordance with the Japanese Classification of Colorectal Carcinoma: A multi-institutional study. S. Noura1, M. Ohue1, J. Hasegawa1, M. Hirota1, T. Matsumura1, Y. Ito2, N. Miyoshi3, H. Kobayashi4, K. Kotake5, K. Sugihara6 1 Surgery, Osaka Rosai Hospital, Sakai, Osaka, Japan, 2Cancer Control and Statistics, Osaka Medical Center for Cancer and Cardiovascular Dideases, Osaka, Japan, 3Surgery, Osaka Medical Center for Cancer and Cardiovascular Dideases, Osaka, Japan, 4Surgery, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan, 5Surgery, Tochigi Cancer Center, Utsunomiya, Japan, 6Surgery, Tokyo Medical and Dental University, Tokyo, Japan Background: Peritoneal metastasis of colorectal cancer (CRC) is often discovered during initial surgery. The aim of this study is to propose a new staging system that could be used to help determine the management. Methods: We evaluated a total of 766 Stage IV CRC patients with synchronous peritoneal metastasis. According to the Japanese Classification, we divided the peritoneal metastasis into P1, P2, and P3. We distinguish distant metastasis from liver metastasis and peritoneal metastasis. According to the Cox proportional hazard model, we construct a new staging group. Results: According to a comparison of the R2 statistics, the combination of liver metastasis and peritoneal metastasis was selected as the final variables. Next, we defined P1H(-) as Grade A, P2H(-) as Grade B, and other groups as Grade C. Our proposed new stage (AIC, 7338.82; c-index, 0.644; R2, 0.123) could thus divide the patients into different prognostic group more clearly than the current Japanese Classification (AIC, 7373.89; c-index, 0.619; R2, 0.097). Conclusions: Our proposed new staging system is very simple and easy for general surgeons. This system is useful for determining the appropriate operative strategy for CRC patients with peritoneal metastasis and for estimating the patients’ prognosis. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 178P Additional preoperative chemotherapy between preoperative chemoradiotherapy and surgery in patients with locally advanced rectal cancer A.S. Abdujapparov1, Y.V. Ten2, B.S. Korakhadjaev2 Oncology and Radiological diagnostics, Tashkent Medical Academy, Tashkent, Uzbekistan, 2Proctology, National Cancer Research Center of Uzbekistan, Tashkent, Uzbekistan 1 Background: The aim of this study was to improve long-term results of treatment of resectable rectal cancer stage I - II through the optimization scheme of neoadjuvant chemoradiation therapy. Methods: The study of the efficacy of the developed neoadjuvant method of treatment of colorectal cancer with the use of remote large-fraction radiotherapy (LFRT) SD 5gr, cumulative dose 25gr conducted in patients receiving capecitabine at a dose of 1700 mg/m2 during the entire course of radiation therapy, local intracavitary microwave hyperthermia (MH) 3, 4 and 5 days, and a course of intrarectal administered metronidazole (MTZ) radiosensitizing mixture on days 3 and 5 of the course. Study group: 53 patients with resectable rectal cancer (LFRT þ capecitabine þ MH þ MTZ). Control group: 54 patients with resectable rectal cancer who received the standard neoadjuvant large-fraction radiotherapy. After neoadjuvant treatment, all patients underwent radical resection within 5-7 days. Results: Evaluation of the composition of the study and control groups of patients showed their complete identity for the main prognostic features. In the study group, postoperative complications were seen in 5 (9.4%) cases; in the control group, which received LFRT postoperative complications were seen in 6 (11.1%) cases, respectively. The use of preoperative LFRT in patients receiving capecitabine, microwave hyperthermia and metronidazole has increased the 5-year survival rate to 69.8%, compared with the control group, receiving LFRT, where the 5-year survival rate was 61.5%. The incidence of local recurrence was 2.2%, and the frequency of distant metastases of 9.6% in the study group, and in the control group of local recurrence rate of 2.6%, and distant metastasis rate of 11.6%. Conclusions: The neoadjuvant treatment method using (LFRT þ capecitabine þ MH þ MTZ) in the combination therapy of resectable rectal cancer does not affect the intra and postoperative frequency of complications and increases the 5-year survival compared with that in patients who received standard neoadjuvant LFRT. Legal entity responsible for the study: Navruzov S.N. Funding: Government Disclosure: All authors have declared no conflicts of interest. 180P J.H. Choi1, S.E. Park2, C.H. Choi2, J.W. Kim2, B.G. Kim3, J.S. Jang2, I.G. Hwang2 1 Radiation Oncology, Chung-Ang University Hospital, Seoul, Republic of Korea, 2 Internal Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea, 3 General Surgery, Chung-Ang University Hospital, Seoul, Republic of Korea Background: The aim of this study is evaluate the efficacy and the safety of addition 4week chemotherapy with 5-Fluorouracil (5-FU) and leucovorin (LV) during the resting periods between preoperative chemoradiotherapy (CRT) and surgery in patients with locally advanced rectal cancer. Methods: Preoperative CRT was delivered to the whole pelvis a 45 Gy in 25 fractions and a 5.40 Gy boost within gross tumor with concurrent 5-FU or capecitabine for 6 weeks. Patients received additional preoperative chemotherapy two cycles of 5-FU and LV (LV 200mg/m2 and 5-FU bolus 400mg/m2 on day 1, and 5-FU infusion 2400mg/m2 for 46hrs, every 2 weeks) after preoperative CRT. Surgery was performed 24 weeks following the completion of preoperative chemotherapy. Results: Between 2009 March and 2015 January, 32 patients were enrolled and surgery, 31 patients completed the scheduled treatment. Pathologic complete remission (pCR) was noted in 4 patients (15.6%) and down-staging was observed in 16 (50%). T downstaging and N down-staging were observed in 20(62.5%) and 19(59.4%), respectively. Grade 3 to 5 toxicity was noted 2 patients (6.2%). The pCR rate was similar with the pCR rates obtained after conventional preoperative CRT, but down staging rate was improved. Conclusions: This study showed that additional 4-week chemotherapy with 5-FU and LV during resting periods after 6-week preoperative CCRT is well tolerable and active and compares favorably with conventional preoperative CRT. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. ix56 | abstracts The results of neoadjuvant chemoradiation therapy in combined treatment of rectal cancer Clinical outcome of anal squamous cell carcinoma treated with chemoradiotherapy with 5-fluorouracil plus mitomycin C A. Doi, H. Bando, A. Kawazoe, S. Fukuoka, Y. Kuboki, K. Shitara, W. Okamoto, T. Kojima, T. Doi, A. Ohtsu, T. Yoshino Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan Background: Anal squamous cell carcinoma (ASCC) is a rare disease accounting for only 2.5% of digestive cancer in the US and probably more less of it in Japan. Established standard treatment for non-metastatic ASCC is concurrent chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) plus mitomycin C (MMC) and it have been reported that complete response (CR) rate is approximately 80%. 5-year disease-free survival (DFS) and overall survival (OS) in RTOG-9811 trial were 68% and 78%, respectively. However there were a few reports regarding the clinical outcome in Japanese patients receiving this CRT regimen. Methods: We retrospectively investigated safety and efficacy in patients with ASCC who received definitive CRT with RTOG-9811 regimen from Apr 2007 to Apr 2015 in our hospital. Adverse event (AE) was assessed with CTCAE version 4.0 and Response was evaluated according to the RECIST version 1.1 criteria. CR was defined as no residual cancer on both CT scan and colonoscopy. DFS and OS were assessed with Kaplan-Meier method. Results: 18 patients were treated in our hospital. Median age was 65 years and 72% were female; clinical stage (AJCC/UICC) I/II, 56% and stage IIIA/IIIB, 44%. Median relative dose intensities of both drugs were 100% (range 50 to 100%). Although 28% of patients temporally interrupted RT with a median interrupted period of 2 days (2-17 days), 94% of patients completed the planned schedule. The main reason for dose modification or RT interruption was neutropenia. The CR rate was 89% and median time to CR from CRT initiation was 17.2 weeks. 3-year DFS rate was 75.9% and 3-year OS rate was 87.2%. CR rate, 3-year DFS and 3-year OS rate were equivalent to previous reports. The most common grade 3/4 AEs were leukopenia (67%) and neutropenia (61%), which are similar to those of RTOG-9811 trial (neutropenia: 61%). Although oral opioids was initiated or increased in 56% of patients during CRT for AE, all patients were recovered to opioid-free. There was no treatment-related death. Although 67% of any grade anal pain and 22% of grade 3/4 radiation dermatitis were observed, both adverse events were manageable by opioids use. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology Conclusions: Concurrent CRT with 5-FU plus MMC was well tolerable and effective for Japanese patients. Legal entity responsible for the study: N/A Funding: N/A Disclosure: H. Bando: AstraZeneca. T. Yoshino: GlaxoSmithKline Boehringer Ingelheim. All other authors have declared no conflicts of interest. 181P Initial CEA and CA19-9 level were associated with pathologic outcome of locally advanced rectal cancer after neoadjuvant chemotherapy with or without radiotherapy: Results from a prospective study Results: Among 104 patients who underwent PET/CT scan for rising CEA values, 59.6% patients were found to have recurrent disease. At CEA level < 5ng/ml, 5.1-10 ng/ ml, 10.1-15 ng/ml, 15.1-50 ng/ml and >50 ng/ml, disease recurred in 10%, 45%,70%,94% and 100% of patients, respectively. Sensitivity, specificity, positive predictive value and negative predictive value of PET/CT scan were 92.7%,95.2%,96.2% and 90.9%, respectively.CEA elevation during follow-up was indicative of recurrence in 68% of secretors and 45% of non-secretors (based on baseline CEA status). Conclusions: In the setting of rising CEA levels during follow-up of colorectal cancer patients, PET/CT scan is a valuable tool to detect recurrence, irrespective of the baseline CEA secretor status. Legal entity responsible for the study: Karthik Chandra Funding: N/A Disclosure: All authors have declared no conflicts of interest. J. Zhang1, Y. Cai1, H. Hu1, J. Xiao1, J. Ling1, Z. Wu2, Y. Deng1 Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, 2Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 1 Background: Fluorouracil based chemoradiotherapy was the standard treatment for locally advanced rectal cancer. Due to the low incidence of local failure with total mesorectal excision and the severity damage of radiotherapy, we aimed to find out the subgroup of rectal cancer patients who might omit radiotherapy, for whom, preoperative enhancement chemotherapy was sufficient. Methods: From Jan 2011 to Feb 2015, complete data was available for 309 patients with rectal cancer who received neoadjuvant chemotherapy with or without radiotherapy followed by TME enrolled in FOWARC study. According to the initial level of CEA and CA19-9, patients were categorized into 3 groups: Group A (high CEA and high CA199); Group B (high CEA or CA19-9); Group C (low CEA and CA19-9). The pathological complete response (pCR) rate, tumor downstaging rate (ypStage 0-I) and the tumor regression grade (TRG) among each group were analyzed basing on different preoperative treatment (chemoradiotherapy vs. chemotherapy). Results: Among 309 patients, there were 24, 96 and 189 patients in group A, B and C, respectively. In group A, 14 patients received CRT and 10 patients had CT. The pCR rate was 7.1% vs. 0 (p ¼ 0.38) and the downstaging rate (ypStage 0-I) was 21.3% vs. 30.0% (p ¼ 0.63), the TRG 0-1 was 64.3% vs. 40.0% (p ¼ 0.24), respectively. In group B, 69 patients underwent CRT and 27 had CT. The pCR rate was 21.7% vs. 14.8% (p ¼ 0.44), the downstaging rate was 33.3% vs. 40.7% (p ¼ 0.49) and the TRG 0-1 was 47.8% vs. 25.9% (p ¼ 0.0503). While in group C, 109 patients received CRT and 80 patients underwent CT. The pCR rate was 26.6% vs. 6.3% (p ¼ 0.0003), and the downstaging rate was 55.1% vs. 41.2% (p ¼ 0.06). The TRG 0-1 was 66.1% vs. 36.2% (p ¼ 0.00004). Conclusions: Preoperative radiotherapy seem to be insensitively to patients with high initial level of CEA and/or CA19-9. The pathological outcome was similar between CRT group and CT group. While in patients with normal CEA and CA19-9, radiotherapy was much more important. The pathological outcome was much better in the group of CRT than that of CT group. Clinical trial indentification: NCT01211210 Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 182P Serum CEA directed PET-CECT scan strategy for followup of colorectal cancer post curative therapy K.C. Vallam1, G. Channabasavaiah2, A. Agarwal3, V. Rangarajann3, V. Ostwal4, R. Engineer5, A. Saklani6 1 Surgical Oncology, Mahatmagandhi Cancer Hospital and Research Institute, Visakhapatnam, India, 2Surgical Oncology, Caritas Cancer Institute Kottayam, Kottayam, India, 3Nuclear Medicine, Tata Memorial Hospital Centre, Mumbai, India, 4Medical Oncology, Tata Memorial Hospital Centre, Mumbai, India, 5 Radiation Oncology, Tata Memorial Hospital Centre, Mumbai, India, 6Surgical Oncology, Tata Memorial Hospital Centre, Mumbai, India Background: As per existing guidelines, during the follow-up of surgically resected colorectal cancer, PET-CT is indicated for asymptomatic elevation of CEA>5ng/ml and no obvious site of recurrence on clinical examination and basic imaging. As an instituitional policy, PET-CECT scan was being performed at our institute whenever 1)CEA levels rose above 5 ng/ml and 2)whenever there was doubling of CEA value (even if CEA was <5 ng/ml). Our aim was to correlate range of CEA elevation with recurrence rates and to evaluate the diagnostic utility of PET/CT scan in this setting. Methods: We retrospectively analysed all cases where a PET-CT scan was performed for elevated CEA during the post treatment period after complete resection of the primary tumour with adjuvant therapy. Study period was from January 1,2013 to July 31, 2015. Volume 27 | Supplement 9 | December 2016 183P Importance of carcinoembryonic antigen on disease control and survival in elderly rectal cancer patients with comorbid condition T. Koo1, H. Bae2, M-Y. Lee2, H.C. Park3, S.W. Lim3 Radiation Oncology, Chuncheon Sacred Heart Hospital, Hallym University, Chuncheon, Republic of Korea, 2Radiation Oncology, Hallym University Medical Center, Hallym University College of Medicine, Anyang, Republic of Korea, 3 Surgery, Hallym University Medical Center, Hallym University College of Medicine, Anyang, Republic of Korea 1 Background: Neoadjuvant chemoradiotherapy and total mesorectal excision (TME) is the standard treatment for rectal cancer. In elderly patients with rectal cancer, however, varied treatment methods are used considering age and underlying diseases. We aimed to analyze treatment outcomes and evaluate prognostic factors in rectal cancer patients aged of 65 years and older, who received TME alone or combined modality treatment. Methods: Medical records of 273 patients with stage II-III rectal cancer who underwent TME in Hallym Sacred Heart Hospital from 2006 and 2014 were retrospectively reviewed. Of these, 93 patients with 65 years and older age were included in this study. Neoadjuvant or adjuvant chemoradiotherapy was given in 38 patients, adjuvant chemotherapy was administered in 32 patients, and TME alone was performed in 23 patients. The age-adjusted Charlson comorbidity index (ACCI) was used to quantify comorbid condition of patients. Results: Median follow-up time was 48.9 months in surviving patients. Five-year overall survival (OS), progression-free survival (PFS), and locoregional PFS (LPFS) were 66.1%, 69.2%, and 81.4%, respectively. In multivariate analyses, elevated initial carcinoembryonic antigen (CEA) level (>5 ng/ml) was an independent prognostic factor of OS (hazard ratio [HR] 2.716, p ¼ 0.007) and PFS (HR 3.582, p ¼ 0.001). High ACCI (4) was associated with OS (HR 2.469, p ¼ 0.050) alone. cT stage (cT4) have an association with LPFS (HR 4.819, p ¼ 0.041). When the patients with low ACCI were divided into two groups according to initial CEA level, the high CEA group had poorer survival than the low CEA group (HR 5.766, p ¼ 0.046). Conclusions: In this study, the initial CEA level was a useful prognostic factor encompassing disease progression as well as survival in elderly rectal cancer patients with curative resection. The patients might receive insufficient treatment when comorbidities were considered alone. The decision of treatment modality could be more optimized with the use of initial CEA level in elderly rectal cancer patients. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 184P Clinical significance of discordance between carcinoembryonic antigen levels and RECIST in metastatic colorectal cancer I-H. Kim, J.W. Jeong, J.H. Yang, S.M. Ro, M.A. Lee Medical Oncology, Internal Medicine, Seoul St. Mary’s Hospital, of the Catholic University, Seoul, Republic of Korea Background: To evaluate the prognostic and predictive values of carcinoembryonic antigen (CEA) patterns that are inconsistent with RECIST responses in metastatic colorectal cancer. Methods: We retrospectively evaluated 412 patients with at least one measurable lesion who received first-line palliative chemotherapy. CEA-response was defined as CEAcomplete response (CR; CEA normalization), CEA-partial response (PR; 50% decrease in CEA levels), CEA-progressive disease (PD; 50% increase in CEA levels), and CEA-stable disease (SD; non-CR/PR/PD). Overall survival (OS) and progressionfree survival (PFS) were evaluated according to CEA-response. doi:10.1093/annonc/mdw581 | ix57 abstracts Results: In RECIST-PR patients, poorer CEA-response was associated with disease progression at the subsequent evaluation. In RECIST-SD patients, CEA-CR and -PR were associated with less disease progression than CEA-PD at the subsequent response evaluation. The correlation of survival outcomes and CEA-response in the same RECIST patients was assessed. In RECIST-PR patients, discordant CEA-response (CEA-PD/SD) portended poorer survival than CEA-CR/PR (median OS and PFS: 42.2 and 15.4 [CEA-CR], 29.5 and 13.9 [CEA-PR], 21.0 and 12.1 [CEA-SD], and 14.7 and 7.4 [CEA-PD] months, respectively; all P < 0.001). In RECIST-SD patients, favourable CEA-response demonstrated better OS and PFS (median OS and PFS: 31.4 and 11.6 [CEA-CR], 23.0 and 12.0 [CEA-PR], 16.6 and 8.4 [CEA-SD], and 12.1 and 5.3 [CEAPD] months, respectively; all P < 0.001). In RECIST-PD patients, OS was not significantly different according to CEA-response. Multivariate analysis demonstrated that discordant CEA-response is a powerful prognostic factor for RECIST-PR and RECIST-SD patients. Conclusions: Among patients of the same RECIST-response, CEA-response patterns are significantly prognostic and strongly predictive of subsequent evaluation outcomes. Legal entity responsible for the study: The Catholic University of Korea College of Medicine Funding: N/A Disclosure: All authors have declared no conflicts of interest. 185P Prognostic impact of tumor location and use of monoclonal antibodies in patients with metastatic colorectal cancer M. Nakamura, T. Onikubo, K. Nakamura, K. Tauchi Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto, Japan Background: Combination of cytotoxic agents and monoclonal antibodies (mAbs; bevacizumab, cetuximab and panitumumab) are recommended as first line therapy for metastatic colorectal cancer (mCRC) in guidelines. On the other hand, recent clinical data suggests that the location of colorectal tumor (i.e. proximal vs. distal colon) may have prognostic value and also have predictive impact for the effect of mAbs. To investigate the correlations among tumor location, use of mAb in first line chemotherapy and overall survival (OS), we conducted a retrospective analysis. Methods: Patients who underwent first line therapy with doublet or triplet cytotoxic drugs for mCRC in our hospital are eligible for this study. Cecum and ascending colon were categorized as “right-side”. Descending colon, sigmoidal colon and rectum were categorized as “left-side”. Transverse colon was excluded from this analysis. In case of multicentric mCRC, the patient was included to the group which more advanced tumor was existed. Results: From March 2006 to April 2016, 279 mCRC patients were enrolled in this study. The median duration of follow-up was 61.6 months (mos). M/F¼170/109. Median age was 66 (31-89). The number of oxaliplatin based regimen, irinotecan based regimen and FOLFOXIRI was 257, 19 and 3, respectively. In 169 patients, mAbs were used in first line therapy (bevacizumab 112, anti-EGFR mAb 57). OS of all eligible patients was 31.5 mos. OS with mAbs was statistically longer than without mAbs (34.3 mos v.s. 27.8 mos; p ¼ 0.006). There was no difference between bevacizumab and antiEGFR mAb (33.4mos v.s.35.0mos, p ¼ 0.913). OS of left-side was statistically longer than right-side (35.9 mos v.s. 19.3 mos; p < 0.001). In right-side, OS with and without mAbs were 19.6 mos and 17.4 mos, respectively (p ¼ 0.546), and there was no difference between beacizumab and EGFR mAb (20.9 mos and 16.4 mos; p ¼ 0.268). In left-side, OS with mAb was statistically longer than without mAbs (42.9 mos v.s. 30.7 mos; p ¼ 0.008), and there was no difference between bevacizumab and anti-EGFR mAb (42.0 mos and 41.8 mos; p ¼ 0.692). Conclusions: In mCRC, tumor location has prognostic impact. Adding mAbs to first line chemotherapy significantly improved OS, and the effect was observed especially in left-side. Legal entity responsible for the study: Aizawa Hospital Funding: Aizawa hospital Disclosure: All authors have declared no conflicts of interest. ix58 | abstracts Annals of Oncology 186P Bevacizumab in combination with 5-fluorouracil (5-FU) based doublet chemotherapy as neoadjuvant therapy for Chinese patients with previously untreated, unresectable liver-only metastatic colorectal cancer: A multi-center, single-arm phase II study D-S. Wan1, S-Z. Zhang2, Y-Z. Chen3, J. Xu4, K-X. Tao5, G-Y. Wang6, C-Y. Hao7 Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China, 2Department of Colorectal Surgery, 2nd Affiliated Hospital of Zhejiang University University School of Medicine, Hangzhou, China, 3 Department of Colorectal Surgery, Liaoning Cancer Hospital & Institute, Shenyang, China, 4Department of Colorectal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China, 5Department of Gasintestional Surgery, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, China, 6Department of Colorectal Surgery, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China, 7Department of Surgery, Peking University Cancer Hospital-Beijing Cancer Hospital, Beijing, China 1 Background: Pts with untreated unresectable liver-only metastases who benefited from perioperative chemotherapy plus BV was still not well known in Chinese mCRC pts. This open label, multi-center pilot study was primarily aimed to assess the R0 resection rate for selected initially unresectable liver-only mCRC pts. Methods: Unresectable liver-only mCRC pts aged 18-75 years, ECOG PS 0-1, with no previous treatment against liver metastases were eligible. If pts had converted to be resectable, he or she took the surgery 6 weeks after the last administration of BV. The last cycle of chemotherapy pre-surgery was given without BV. Pts who took the surgery were restart the chemotherapy and BV 4 weeks after the surgery and after complete wound healing. The total number of cycles given pre and post-surgery was 12. The last cycle of chemotherapy given without BV pre-surgery was not included in the 12 combined cycles. This single-arm phase II study design was applied with R0 rate as the primary end point, and 50 pts required. We also assessed ORR, PFS, DFS and Safety as secondary objectives. Results: 50 pts (median age 56.1 years (37–73); ECOG PS 0-1: 82%) were enrolled from 7 centers. Of these 17 pts underwent surgery, with a R0 resection rate of 30.0% (95% CI: 17.9%-44.6%). ORR was 30.0% (95% CI: 17.9%-44.6%). Additional, mPFS was 9.3 months (95% CI, 6.5–12.4) for all 50 patients and the median DFS was 8.1 months (95% CI, 6.5–12.4) for 17 pts undergoing study defined surgery. The common BV related AEs (incidence rate > ¼5%) were reported as neutrophil count decreased (14.0%), hypertension (12.0%), bone marrow failure (8.0%), and white blood cell count decreased (6.0%). Six AEs of special interest were reported from 5 patients (10.0% of 50 patients) and all were hypertension with CTC Grade > ¼ 3. Conclusions: Neoadjuvant chemotherapy with BV showed high resection rate and response rates in Chinese untreated, unresectable liver-only mCRC pts. The toxicity is well tolerated. The study is continued as scheduled, to further evaluate the benefit of overall survival and quality of life. (Clinical Trail No. NCT01695772) Clinical trial indentification: Clinical Trail No. NCT01695772 Legal entity responsible for the study: Roche Funding: Shanghai Roche Pharmaceutical Ltd. Disclosure: All authors have declared no conflicts of interest. 187P Optimal treatment strategy of first-line oxaliplatin (Oxa)containing therapy in metastatic colorectal cancer (mCRC): A trial-level meta-analysis T. Moriwaki1, M. Gosho2, A. Sugaya1, T. Yamada1, Y. Yamamoto1, I. Hyodo1 Faculty of Medicine, Division of Gastroenterology, University of Tsukuba, Tsukuba, Japan, 2Faculty of Medicine, Department of Clinical Trial and Clinical Epidermiology, University of Tsukuba, Tsukuba, Japan 1 Background: The treatment strategy of Oxa-containing therapy, which is comprised of induction therapy (IT) followed by maintenance therapy without Oxa, and then considering Oxa reintroduction (ReOxa), is recognized as an option in mCRC patients because of particularly Oxa induced chronic peripheral neuropathy. However, the optimal duration of IT and number (No.) of maintenance drugs (MDs) and the need for ReOxa are unclear. Methods: We conducted a literature search of phase II and III trials of first-line Oxacontaining chemotherapy including maintenance therapy for mCRC that were presented up to March 2016, and investigated relationships between median overall survival (OS) and duration of IT, No. of MDs, and ReOxa rate using correlation analysis and weighted multivariate regression analysis. Results: Twenty-seven treatment arms were identified among 18 trials and a sample size of 3,109 patients was analyzed. IT was 11 chemotherapy alones and 16 chemotherapy þ targeted agents. Median duration of IT was 18 weeks (range, 12 to 27). No. of MDs was 0 in 8 treatment arms, 1 (FU or targeted agent) in 11 treatment arms, and 2 (FU þ targeted agent) in 9 treatment arms. Median ReOxa rate was 30.9% (range, 0 to 100). Median OS was 23.2 months (range, 15.8 to 31.0). Duration of IT was weakly correlated with OS (Spearman’s partial correlation coefficient, r ¼ 0.14). No. of MDs was moderately correlation with OS (r ¼ 0.60). ReOxa rate was weakly correlation with OS (r ¼ 0.07). In Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology multivariate regression analysis, No. of MDs was significantly correlated with OS (P ¼ 0.004). There was a significant interaction between duration of IT and No. of MDs (P ¼ 0.014). The longest predicted OS was the treatment strategy comprised of IT for 12 weeks and 2 MDs when IT for 12–24 weeks and 0–2 MDs were applied to the model. Conclusions: The strongest correlation with improvement of OS was the maintenance therapy using FU þ targeted agent. The optimal treatment strategy of Oxa-containing therapy may be comprised of IT for 12 weeks followed by two MDs, not considering ReOxa in first-line setting for mCRC. Legal entity responsible for the study: National university corporation Funding: Division of Gastroenterology Disclosure: All authors have declared no conflicts of interest. 188P The efficacy of neoadjuvant chemotherapy in patients with advanced colon cancer Y. Lv, G. Dai Medical Oncology Department 2, PLA General Hospital, Military General Hospital of Beijing (PLA), Beijing, China Background: This study aimed to investigate the efficacy studies of neoadjuvant chemotherapy in patients with advanced colon cancer. Methods: 160 colon cancer patients were randomly assigned to an adjuvant chemotherapy group (n ¼ 80) or a control group (n ¼ 80) from January 2011-June 2015. The preoperative chemotherapy group were treated with FOLFOX chemotherapy for 4 cycles. The preoperative chemotherapy group underwent radical surgery after chemotherapy ended on 21d. The control group underwent radical surgery which did not work. Two groups were treated postoperatively with 4 cycles of chemotherapy. The treatment effect of two groups were compared. Results: The staging grade of the preoperative chemotherapy group were lower than the control group (P < 0.05). The tumor diameter, and theoperative times, the average length of stay, number of lymph nodes dissected, blood loss of two groups showed no significant difference (P > 0.05). The excision rate of the adjuvant chemotherapy group was higher than the control groups (P < 0.05). The omental adhesions, intestinal obstruction, intestinal edema peripheral tissues, intestinal mucosa hyperemia were lower than the control group (P < 0.05). Two groups of patients were followed up for 12 to 36 months; the survival rate of adjuvant chemotherapy group was higher (P < 0.05), while the pathological staging, and recurrence rate were lower than in the control group (P < 0.05). Conclusions: Preoperative neoadjuvant chemotherapy in patients with advanced colon cancer can improve the resection rate and long-term survival and reduce the recurrence rate. Legal entity responsible for the study: Medical Oncology Department 2, PLA General Hospital Funding: Medical Oncology Department 2, PLA General Hospital Disclosure: All authors have declared no conflicts of interest. 189P Phase II trial of S-1 plus panitumumab for wild-type KRAS unresectable colorectal cancer patients previously treated with 5-fluorouracil (5-FU), oxaliplatin and irinotecan (KSCC1103) Y. Sakamoto1, Y. Yoshida2, H. Ishikawa3, T. Ohchi4, H. Takeshita5, Y. Emi6, H. Komatsu7, T. Sawai8, T. Shimose9, E. Oki10, H. Saeki11, Y. Kakeji12, Y. Yoshida13, H. Baba14, Y. Maehara10 1 Department of Gastroenterological Surgery, Kumamoto University, Kumamoto, Japan, 2Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan, 3Gastorointestinal Surgery, Sasebo City General Hospital, Nagasaki, Japan, 4Surgery, Kurume University School of Medicine, Kurume, Japan, 5Surgical Oncology, Nagaski University Hospital, Nagasaki, Japan, 6 Surgery, Saiseikai Fukuoka General Hospital, Fukuoka, Japan, 7Surgery, Japan Community Health Care Organization Isahaya General Hospital, Isahaya, Japan, 8 Division of Nursing, Nagasaki University School of Health Sciences, Nagasaki, Japan, 9Gastorointestinal Surgery, Clinical Research Support Center Kyushu, Fukuoka, Japan, 10Gastroenterological Surgery, Kyushu University Hospital, Fukuoka, Japan, 11Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan, 12Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan, 13Gastroenterological Surgery, Kurume University, Kurume, Japan, 14Gastroenterological Surgery, Kumamoto University, Kumamoto, Japan Background: Anti-epidermal growth factor receptor antibody is been a promising third-line regimen for wild-type RAS patients who have already treated with oxaliplatin- and irinotecan-based regimens. The purpose of this phase II study is to explore the efficacy and safety of S-1 plus panitumumab for the wild-type KRAS Volume 27 | Supplement 9 | December 2016 unresectable colorectal cancer patients who have been previously treated with key drugs for colorectal cancer, such as 5-FU, oxaliplatin and irinotecan. Methods: Wild-type KRAS unresectable colorectal cancer patients who were treated by key drugs were enrolled in this study. They protocol regimen consisting of oral S-1 4080 mg twice daily was administered on days 1 to 28 every 6 weeks followed by a 2-week rest period plus intravenous panitumumab 6 mg/m2 every 2 weeks until disease progression. The primary endpoint was progression-free survival. Results: Of the thirty-two patients enrolled in this study, twenty-eight patients were analyzed for efficacy, because four patients had to be excluded due to their short washout period. The most frequent hematological adverse event was anemia (any grade: 81.3%, grade 3/4: 9.4%). Other common severe adverse events (Grade 3/4) were skin rash (31.3%), anorexia (18.8%) and diarrhea (9.4%). Response rate and disease-control rate were 17.9% (95% confidential interval: 6.1-36.9%) and 50.0% (95% C.I.: 30.769.4%), respectively. Six-month and 1-year progression-free survival (PFS) rates were 25.9% (90% C.I.: 13.4-40.3%) and 7.4% (90% C.I.: 1.8-18.4%), respectively. Median PFS time was 4.0 months (90% C.I.: 2.76-5.42 months). The one-year overall survival (OS) rate was 47.6% (95% C.I.: 28.1-64.9%). Median survival time was 11.9 months. Conclusions: This trial couldn’t show the efficacy of S-1 plus panitumumab since the lower limit of median PFS lowered than threshold. While a small number of pts indicate that this conclusion be viewed with caution, S-1 plus panitumumab induced high incidence of Grade 3 skin rash. Serious drug interaction between S-1 and panitumumab might increase the risk of skin toxicity. Clinical trial indentification: UMIN000007274 Legal entity responsible for the study: N/A Funding: Kyushu Study group of Clinical Cancer Disclosure: All authors have declared no conflicts of interest. 190P Observational cohort study of 1st line bevacizumab combined with chemotherapy in metastatic colorectal cancer (HGCSG0802): Sub-group analysis by the Glasgow Prognostic Score (GPS) T. Sasaki1, S. Yuki2, Y. Kawamoto3, K. Harada3, T. Meguro1, T. Miyagishima4, M. Nakamura5, A. Sato6, I. Iwanaga7, M. Tateyama8, K. Hatanaka9, K. Eto10, H. Okuda11, O. Muto12, M. Abe13, A. Oba14, S. Kato15, K. Miyashita16, Y. Sakata17, Y. Komatsu3 1 Internal Medicine, Hokkaido Gastroenterology Hospital, Sapporo, Japan, 2 Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan, 3Cancer Center, Hokkaido University Hospital, Sapporo, Japan, 4 Medical Oncology, Kushiro Rosai Hospital, Kushiro, Japan, 5Gastroenterology, Sapporo City General Hospital, Sapporo, Japan, 6Medical Oncology, Hirosaki University Hospital, Hirosaki, Japan, 7Medical Oncology, Japanese Red Cross Kitami Hospital, Kitami, Japan, 8Internal Medicine, Tomakomai Nisshou Hospital, Tomakomai, Japan, 9Gastroenterology, Hakodate Municipal Hospital, Hakodate, Japan, 10Gastroenterology, Tomakomai City Hospital, Tomakomai, Japan, 11Medical Oncology, Keiyukai Sapporo Hospital, Sapporo, Japan, 12 Medical Oncology, Japanese Red Cross Akita Hospital, Akita, Japan, 13 Medical Oncology, Sapporo Kosei General Hospital, Sapporo, Japan, 14 Gastroenterology, Iwamizawa Municipal General Hospital, Iwamizawa, Japan, 15 Gastroenterology, Sapporo Hokuyu Hospital, Sapporo, Japan, 16 Gastroenterology, Aiiku Hospital, Sapporo, Japan, 17Misawa City Hospital, Misawa, Japan Background: The Glasgow Prognostic Score (GPS), combination of C-reactive protein and albumin, has reported its prognostic value in metastatic colorectal cancer patients receiving cytotoxic agents. However, the validity of the GPS has not been reported in patients treated with bevacizumab (Bev)-based first line chemotherapy. Methods: 115 patients with mCRC treated with Bev contained first line chemotherapy were registered from 15 centers in Japan. Univariate and multivariate analysis for overall survival (OS) were performed using patient characteristics. Survival analyses were performed with the Kaplan-Meier method, log-rank test and the Cox proportional hazards model. The analysis was also designed to determine whether the GPS could be extended to progression-free survival (PFS). Results: All data were available for prognostic categorization in 97 patients. Patients with the GPS of 0, 1 and 2 were 58, 23, and 16, respectively. The pts characteristics between 0 and 1/2 were generally balanced except for prior colorectomy (70.7% in 0, 51.3% in 1/2; p ¼ 0.058), disease status (primary unresectable) (79.3% in 0, 97.4% in 1/2; p ¼ 0.013), liver metastasis (58.6% in 0, 84.6% in 1/2; p ¼ 0.007), KRAS exon2 status (wild) (70.7% in 0, 51.3% in 1/2; p ¼ 0.058) and median number of metastatic organ (mean; 1.78 in 0, 2.21 in 1/2; p ¼ 0.040). The distribution and median OS/PFS for the GPS were as follows: 0 (n ¼ 58; 29.9/10.4 months), 1/2 (n ¼ 39; 17.0/7.3 months). For OS and PFS, there were significant difference between 0 and 1/2 (p < 0.001/p¼0.004). In the Cox multivariate analysis, GPS had shown an independent prognostic impact (GPS 0 vs 1/2; HR 2.158, p ¼ 0.005) and predictive impact (GPS 0 vs 1/2; HR 1.819, p ¼ 0.021). doi:10.1093/annonc/mdw581 | ix59 abstracts Conclusions: It was shown that GPS might provide valuable information in the bevacizumab combined first line chemotherapy for patients with mCRC. Legal entity responsible for the study: Nonprofit Organization: Hokkaido Gastrointestinal Cancer Study Group Funding: Nonprofit Organization: Hokkaido Gastrointestinal Cancer Study Group Disclosure: T. Sasaki: Honoraria: Chugai Pharmaceutical. S. Yuki: Honoraria: Taiho Pharmaceutical, Merck Serono, Bristol-Myers Squibb, Takeda Pharmaceutical, Chugai Pharmaceutical, Bayer Yakuhin, Eli Lilly Japan. Y. Sakata: Honoraria: Taiho Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Merck SeronoOno Pharmaceutical, Nikkei Business Publications. Y. Komatsu: Honoraria and/or Research fund: Taiho Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, Merck Serono, Pfizer Japan, Ono Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Eli Lilly Japan, Novartis Pharma, Kureha Corporation. All other authors have declared no conflicts of interest. 191P Safety and preliminary efficacy of modified FOLFOXIRI in advanced colorectal cancer: Single institution experience Y. Cai1, H. Hu2, J. Zhang2, L. Yang2, Z. Wu2, Y. Deng3 Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, 2Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, 3Medical Oncology, Sun Yat-sen University, Guangzhou, China 1 Annals of Oncology Results: A total of 293 patients were involved, 151 female (51.53%) and 142 male (48.46%). Median age was 52 years (range 19-89).Rectum is the most common site (62.82%). Majority of patients presented with passing blood and mucous stool. The most common histology was adenocarcinoma (62.52%). Adenoma-carcinoma sequence was detected in 29(9.89%). Majority were in stage 2B (38.51%) and metastatic diseases were found in 22.26%.Common metastatic sites were peritoneum and omentum. Among surgically treated patients, 67.23% received radical surgery. Only 58.35% of registered patients took chemotherapy and among them 105 patients (61.4%) received continuous infusion of FU/LV. Grade 3 to 4 neutropenia was observed in 14.47%. Among patients with non-metastatic rectal cancer, only 41.49% were agreed to take EBRT (50 cGy). None of them received neoadjuvant RT. 102 were lost to take further management after surgery and another 35 patients were lost to attend follow-up clinic. Among the rest of the patients, 65.78% were progression free and 34.21% had disease progression or tumour recurrence during follow-up period. Conclusions: Fortunately, majority of patients received radical surgery, the mainstay treatment of CRC. But significant numbers of patients were lost to take further needful management. Advantage of chemotherapy with manageable toxicity can be observed. Strategies to improve patients’ health education and to develop screening program and better advanced treatment are needed to upgrade our CRC care. Legal entity responsible for the study: Medical Oncology Department, Yangon General Hospital. Funding: Medical Oncology Department, YGH. Disclosure: All authors have declared no conflicts of interest. 193P Background: FOLFOXIRI showed higher response in metastatic colorectal cancer.Although it was recommended in selected patients due to its high toxicity. To evaluate the safety and priliminary efficacy of modified FOLFOXIRI (mFOLFOXIRI)for patients with advanced colorectal cancer(CRC). Methods: Data from 242 CRC patients receiving triplet in four trials(NCT02350530, NCT02063529, NCT02217020, NCT02128425)during March 2013 to June 2016 were retrospectively analyzed. Toxicity was graded using NCI-CTCAE. Objective response was evaluated according to the RECIST criteria after at least 4 cycles chemotherapy. Results: In the whole group, median age was 51 years(range 19-72).92 patients(38%) were locally advanced CRC, 150(62%) were metastatic CRC.Only 28(18%) patients received prior operation on primary tumor,37(15%) received target therapy. Main grade 3 or 4 adverse events of patients were neutropenia (n ¼ 86[35.5%]), fatigue (n ¼ 32[13.2%]), anaemia (n ¼ 20[8.3%]), nausea(n ¼ 14[5.8%]), and diarrhea(n ¼ 8[3.3%]) .Grade 2 oxaliplatin-related peripheral neuropathy was rare (n ¼ 1 [2%]). Seven serious adverse events occurred: febrile neutropenia (n ¼ 2 [0.8%]) and intestinal perforation(n ¼ 5 [2.1%], in 3 upper rectum and 2 sigmoid colon) .In cetuximab-combined group, higher rate of stomatitis(n ¼ 1 [5.0%]), diarrhea(n ¼ 2 [10.0%]) and rash(n ¼ 4 [20%]) were noted.In bevacizumab-combined group, one case of deep-vein thrombosis due to implantable venous access port was noted. No treatment-related deaths occurred. 134 patients were assessed for efficacy.Documented complete and partial response were observed in 10 (7.5%) and 103 (76.9%) patients(overall response rate¼84.3%, disease control rate¼96.2%).In total,1220 cycles chemotherapy were administered with a median of 5 cycles per patient (range 1 to 19). 129 courses(10.6%)were delayed for a median of 5 days(range 3-10).Dose reduction was required in 92 cycles(7.5%).The overall relative dose intensity was >90% and for the individual drugs were 94.2% for Fluorouracil, 97.8% for oxaliplatin and 86% for irinotecan. Conclusions: The reducing dosage mFOLFOXIRI can be safely used in advanced colorectal cancer and achieved promising results in terms of short term efficacy. Clinical trial indentification: NCT02350530, NCT02063529, NCT02217020, NCT02128425 Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 192P Colorectal cancer care in Yangon General Hospital H.H. Maw Medical Oncology, Yangon General Hospital, Yangon, Myanmar Background: CRC is the third most common cancer in men and the fourth in woman, in Myanmar. In the past years incidence of CRC steadily increased. So we explored the CRC case-load and line of management to assess the status of CRC care. Methods: This descriptive study was undertaken in Medical Oncology Department in YGH, the main tertiary hospital in our country. All histologically proved CRC cases registered from October 2014 to September 2015 were involved. Data regarding patient’s particulars, clinical presentations, histology, staging, treatment given and outcomes during a median follow-up period 6months (range 4- 14) were recorded. Data analysis was done to describe the results. ix60 | abstracts A phase 1 study evaluating the pharmacokinetics (PK), safety, and efficacy of regorafenib (REG) in Chinese patients with advanced, refractory solid tumors J. Cao1, D. Ji1, W. Shen1, Q. Wang2, Y. Liu2, D. Lu3, I. Sturm4, F. Huang5, A. Cleton4 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, 2Clinical Science, Bayer HealthCare Pharmaceuticals, Beijing, China, 3Data Sciences and Analytics, Bayer HealthCare Pharmaceuticals, Beijing, China, 4Clinical Pharmacology Oncology, Bayer AG, Berlin, Germany, 5 Clinical Pharmacology Oncology, Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA Background: This single-arm phase 1 study was conducted to define the PK of REG and its metabolites, M-2 and M-5, in Chinese patients with advanced solid tumors. Methods: Patients from China mainland with locally advanced/metastatic, refractory solid tumors were enrolled if they were not candidates for standard therapy or if they had metastatic CRC or advanced GIST and REG was a treatment option. The primary objective was PK; secondary objectives were safety, tolerability, and efficacy. Single-dose PK was collected on Cycle 0 Day 1 up to 96 hours after administration of REG 160 mg followed by 6 days off treatment. From Cycle 1 Day 1, REG 160 mg was administered daily on a 3 weeks on/1 week off schedule in a 28-day cycle until tumor progression, toxicity, or withdrawal of consent. Optional multiple-dose REG PK was collected on Cycle 1 Day 21 up to 96 hours post dose where applicable. Results: All 18 patients who received study treatment were valid for single-dose PK, safety, and efficacy analyses; 9 were valid for multiple-dose PK analysis. After singledose REG, the geometric mean AUC(0–tlast) (mgh/L) was 43.1 (REG), 17.1 (M-2), and 3.99 (M-5), with moderate to high inter-individual variability: Geo-CV 63% (REG), 56% (M-2), 74% (M-5). After multiple-dosing, increases in AUC(0–24) and Cmax were observed for the 3 analytes (accumulation ratios: REG, 1.83 AUC(0–24) and 1.61 Cmax; M-2, 3.44 AUC(0–24) and 3.51 Cmax; M-5, 35.8 AUC(0–24) and 21.2 Cmax). The most common drug-related grade 3 treatment-emergent adverse events were hypophosphatemia (39%), lipase increase (22%), and hand–foot skin reaction (22%). The best overall response was stable disease in 10/18 (56%) patients with median overall treatment duration of 9.4 weeks. Conclusions: The inter-individual variability of REG, M-2, and M-5 was moderate to high after single- and multiple-dose REG, with observed accumulation after multiple dosing. Overall, the PK of REG, M-2, and M-5 in patients from China mainland was consistent with that previously reported. The safety profile was consistent with the known safety profile of REG. No safety signals were detected to indicate a potential influence of Chinese ethnicity on the safety profile of REG. Clinical trial indentification: NCT02398513 Legal entity responsible for the study: Bayer Funding: Bayer Disclosure: Q. Wang, Y. Liu, D. Lu, F. Huang: Employee of Bayer. I. Sturm: Employee of Bayer and owns stock in Bayer. A. Cleton: Employee of Bayer and has stock in Bayer, Astrazeneca, Pfizer. All other authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology 194P Efficacy of second line chemotherapy following first line triplet chemotherapy in advanced colorectal cancer (ACRC) A.M. Hakoun1, A.M. Gad2, A. Alzahrani3, A. Aljubran3, S. Bazarbashi3 Research Office Department, Alfaisal University College of Medicine, Riyadh, Saudi Arabia, 2Clinical Oncology Department, Ain Shams University Faculty of medicine, Cairo, Egypt, 3Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia 1 Background: The efficacy of second line therapy after first line triplet in advanced colorectal cancer has not been extensively explored. Methods: Medical records of patients (pts) with ACRC treated on prospective phase I-II study with the combination of oxaliplatin, irinotecan, capecitabine and bevacizumab were retrospectively reviewed. The following data were recorded: Demographics, response to first line chemotherapy, organs involved, type of second line chemotherapy, response to second line chemotherapy, progression free survival (PFS), overall survival (OS), K-ras status, and baseline lab results at second line chemotherapy. Results: Fifty three pts received first line triplets, out of which 28 (52%) received second line chemotherapy. Median survival for pts who received second line vs no second line was 28.0 months (95% CI 22.8-33.2) vs 23.0 months (95% CI 13.2- 32.8) (Log-rank P ¼ 0.693). Of the 28 pts who received second line chemotherapy, 13 were male, 8 had colon primary, 10 had mutant K-tas with 3 unknown, ECOG performance status 1/2/3/ unknown was in 16/3/2/7 pts, organs involved: liver/lung/peritoneum: in 17/16/8 pts. Second line chemotherapy was Xelox/FOLFOX in 13, Xeliri/FOLFIRI in 12 and irinotecan þ cetuximab in 3 pts. Best response was partial in 6 (21.43%), stable disease in 11 (39.29%) and progressive disease in 11 (39.29). Median PFS and OS was 4.8 mo (95% CI 2.4-9.6) and 15 mo (95% CI 9.6-20.4). Univariate analysis of above prognostic factors for survival including type of chemotherapy showed no significance except for elevated CEA (Log-rank P ¼ 0.0074) Conclusions: Second line chemotherapy following first line triplet in ACRC shows equal efficacy compared to reported results following doublets, regardless of the agent used. Elevated CEA at second line chemotherapy confer poor prognosis. Clinical trial indentification: IRB approval #: RAC 2151 096 Legal entity responsible for the study: Office of research affairs at King Faisal Specialist Hospital and Research Center- Riyadh Funding: N/A Disclosure: All authors have declared no conflicts of interest. 195P Irinotecan plus cetuximab (Cmab) versus irinotecan plus panitumumab (Pmab) in patients (pts) with wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC) as thirdline in daily practice N. Sugimoto, A. Hasegawa, F. Fujisawa, T. Yoshinami, T. Yagi, F. Imamura Clinical Onocology, Osaka Medical Center for Cancer and Cardiovascular Dideases, Osaka, Japan Background: The phase 3 ASPECCT trial of pts with chemo-refractory WT KRAS exon 2 mCRC demonstrated that Pmab was noninferior to Cmab for overall survival (OS). But few data was existed the comparison of irinotecan plus Cmab (IC) with irinotecan plus Pmab (IP). So we retrospectively compared the efficacy and toxicity of IC to IP in patients with mCRC as third- line in our hospital. Methods: The selection criteria were pathologically proven mCRC; 20 years or older; WT KRAS exon 2; had a previous treatment history of refractory or intolerable of fluoropyrimidine, oxaliplatin and irinotecan; no prior Cmab and Pmab; performance status 0-2; able to oral intake; and adequate organ functions (excluding WJOG6510G enrolled patients). Results: 44 patients were treated IC or IP over the period from December 2008 to January 2016. The analysis covered 34 patients (excluding enrolled WJOG6510G). The median age was 65 years (range 41-88); 24 males and 10 females; PS 0/1/2 score 19/13/2; 23 patients were treated IC and 11 patients were treated IP. Progression-free survival and overall survival were 3.8 and 9.9 months with IC and 6.0 and 10.5 months with IP (no significant difference). The response rate and disease control rate were 17.4% and 56.6% with IC and 63.6% and 88.9% with IP. The rate of grade 3-4 toxicity in IC/IP were leucopenia (8.7%/18.2%), neutorpenia (4.3%/27.3%), anemia (17.4%/18.2%), rash (4.3%/9.1%), pruritus(8.9%/0%), paronytia(13%/9.1%), hypomagnesaemia(8.7%/ 27.3%) and infusion related reaction (0%/9.1%). There was no treatment death in both groups. Conclusions: It is suggested that not only IC but also IP can be the option for WT KRAS exon 2 mCRC patients as third-line. The result of WJOG6510G (IC versus IP in pts with WT KRAS exon 2 mCRC as third-line; a multicenter, randomized phase II study) will be reported near future. Volume 27 | Supplement 9 | December 2016 Legal entity responsible for the study: Osaka Medical Center for Cancer and Cardiovascular Diseases Funding: N/A Disclosure: All authors have declared no conflicts of interest. 196P Changes in serum p53 antibody levels around the time of surgery and p53 mutations predict the prognosis of colorectal cancer T. Satoyoshi, M. Shiozawa, A. Higuchi, D. Inagaki, K. Kazama, Y. Atsumi Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan Background: A previous study reported that 20-30% colorectal cancer patients are positive for serum p53 antibodies. However, exactly how long-term changes in serum p53 antibody levels reflect the prognosis of colorectal cancer remains unknown. We aimed to determine the clinical significance of changes in serum p53 antibody levels around the time of surgery and p53 gene mutations. Methods: We performed primary colorectal cancer surgery in 245 patients from November 2008 to August 2010. Among them, 209 patients were measured serum p53 antibody before and after surgery. We classified them into four groups to analyze recurrence and 5-year survival rate after surgery. The patient rising serum p53 antibodies after surgery grouped A, decreasing but keeping positive grouped B, changing from positive to negative grouped C, and keeping negative from before surgery grouped D. We also investigated the p53 gene mutation using pathological specimens. Results: Sixty-nine patients became positive for serum p53 antibodies during the course. Of these, 14, 28, and 27 patients belonged to the A, B, and C groups, respectively. The recurrence rate after surgery for 5 years was 85.7%, 32.1%, 7.4%, and 15.7% in the A, B, C, and D groups, respectively. The 5-year survival rate among patients in the A, B, C, and D groups was 41%, 68%, 92%, 91%, respectively (p < 0.0001). Additionally, the p53 gene mutation rate was 49.3% in all patients, and 59.4% in those positive for serum p53 antibody. Conclusions: Colorectal cancer patients showing elevation of serum p53 antibody levels around the time of surgery have a high risk of recurrence. Similarly, as the 5-year survival, an increase in serum p53 antibody levels postoperatively was related to poor prognosis, and negative change indicated a good prognosis. We are going to discuss the association between p53 mutant and serum p53 antibodies. Legal entity responsible for the study: Kanazawa Cancer Center Funding: Kanazawa Cancer Center Disclosure: All authors have declared no conflicts of interest. 197P Tumor-infiltrating lymphocytes predict the chemotherapeutic outcomes in patients with stage IV colorectal cancer M. Shibutani, K. Maeda, H. Nagahara, T. Fukuoka, Y. Iseki, S. Matsutani, T. Tamura, G. Ohira, S. Yamazoe, K. Kimura, T. Toyokawa, R. Amano, H. Tanaka, K. Muguruma, K. Hirakawa, M. Ohira Surgical Oncology, Osaka City University Medical School, Osaka, Japan Background: Anticancer immune response has been reported to contribute the success of chemotherapy. The aim of this study was to evaluate the significance of the measurement of tumor-infiltrating lymphocytes (TILs) in primary tumor as a prognostic marker of the chemotherapeutic outcomes in patients with stage IV colorectal cancer. Methods: A total of 55 patients with stage IV colorectal cancer who underwent palliative chemotherapy after resection of primary tumor were enrolled. Hematoxylin and eosin stained tumor sections were used for evaluation of TILs. The extent of TILs was assessed by measurement of the area occupied by mononuclear inflammatory cells over total intratumoral stromal area at the invasive margin. Moreover, immunohistochemistry for CD8 was performed, and the number of immunoreactive cytotoxic T-lymphocyte (CTL) was counted. Results: Twenty-nine patients were classified into the high TILs group and 26 patients were classified into the low TILs group. The high TILs group had a significantly higher chemotherapeutic response rates (75.0% vs 42.3%, p ¼ 0.026) and better progressionfree survival rates (Median survival time: 10.1m vs 7.3m, p ¼ 0.0235) than the low TILs group. Moreover, the high TILs group had a significantly better overall survival rates than the low TILs group (Median survival time: 35.5m vs 21.3m, p ¼ 0.0300). The extent of TILs and the number of CTL showed a strong association (p < 0.001). Conclusions: The measurement of TILs in primary tumor can be used as a prognostic marker of the clinical effectiveness of palliative chemotherapy in patients with stage IV colorectal cancer. doi:10.1093/annonc/mdw581 | ix61 abstracts Clinical trial indentification: Retrospective study Osaka City University Graduate School of Medicine approved No.926 Legal entity responsible for the study: Masatsune Shibutani Funding: N/A Disclosure: All authors have declared no conflicts of interest. 198P Use of chemotherapy and mismatch repair deficiency testing in resected stage II colon cancer L. Au1, M. Grant2, A. Haydon1, K. Oliva3, S. Wilkins3, E. Segelov4, Y. Antill2, C. Peter3, P. Ranchod3, A. Polglase3, M. Chin3, F. Chip3, S. Skinner5, W. Roger3, P. McMurrick3, J. Shapiro2 1 Medical Oncology, Alfred Hospital, Melbourne, Australia, 2Medical Oncology, Cabrini Health, Melbourne, Australia, 3Department of Surgery, Cabrini Health, Melbourne, Australia, 4St Vincent’s Clinical School, University of New South Wales, Sydney, Australia, 5Department of Surgery, Alfred Hospital, Melbourne, Australia Background: Adjuvant chemotherapy for stage II colon cancer offers a small (2-3%) overall survival benefit and is not universally recommended. Currently, chemotherapy is often discussed with patients at increased recurrence risk based on histological criteria. Mismatch repair deficiency (dMMR) confers an improved prognosis and identifies patients who appear not to benefit from post-operative chemotherapy. Widespread immunohistochemistry testing in Australia began in 2013. Methods: Prospective data were collected on all patients with resected stage II colon cancer between Feb-2010 to Feb-2015 across two large Australian hospitals. Rectal cancers were excluded. Data collected included patient demographics, tumour histology especially presence of high-risk features (<12 nodes, obstruction, perforation, poor differentiation, T4), dMMR testing frequency, chemotherapy use, and outcomes. Results: 355 patients (56.1% female) were analysed. 25 (7.3%) received adjuvant chemotherapy (Cabrini 22/271 vs. Alfred 3/84, 8% vs. 4% p ¼ 0.22). Mean age was 77.9 years. No patient >80 years (52%) received chemotherapy. Presence of 1 high-risk feature increased the likelihood of adjuvant chemotherapy. dMMR testing was performed on 167 patients (47%), most occurred post-2013 (117/160 vs. 50/195 patients). dMMR rates were 34.1%. 2/57 dMMR patients received chemotherapy; both young (34 and 54 years) with high-risk features. 28/355 (7.8%) patients relapsed, including 3/25 (12%) who had received chemotherapy, and 25/330 (6.9%) who did not. 10/28 (36%) of relapses are disease-free post-resection, 9 (32%) alive with metastatic disease, and 9 deceased. An audit of familial cancer clinic referrals and BRAF mutation rate is underway. Conclusions: >50% of patients were >80 years. Uptake of chemotherapy was low (7.3%). Despite this, few relapses were observed (7.8%) and 36% of these underwent successful surgical salvage. dMMR testing should be performed in all stage II colon cancer patients being considered for adjuvant chemotherapy as it will identify a proportion (34.1%) of patients who may not benefit from treatment. Legal entity responsible for the study: N/A Funding: Alfred Hospital and Cabrini Health Disclosure: All authors have declared no conflicts of interest. 199P Circulating tumor DNA as a dynamic marker for disease burden in patients with metastatic colorectal cancer A. Hsu1, H. Hung-Chih2, H-C. Chen1, S-J. Chen1 1 Clinical Sequencing, ACT Genomics Co. Ltd., Taipei, Taiwan, 2Division of hematology-Oncology, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan Background: Metastatic colorectal cancer (mCRC) is one of the most deadly cancer condition worldwide. Currently, treatment monitoring using CT and/or plasma CEA does not offer sufficient sensitivity and cannot be used for certain treatments. This study investigate whether circulating tumor DNA (ctDNA) can be used to monitor treatment efficacy. Methods: Plasma samples were obtained from 16 patients with mCRC before and after treatment. Cell-free DNA were extracted for next-generation sequencing analysis. Matched tumor samples were obtained from 12 patients for concordance analysis. The sequencing panel covers more than 1500 mutation hotspots on 13 cancer-related genes. All ctDNA samples were sequenced with at least 8000X average coverage. The sequenced raw data was aligned to reference human genome to identify variants. Detection sensitivity was set at 0.5%. Results: ctDNA were detected in 12 of 16 (75%) pre-treatment plasma samples, with 8 samples harboring more than one ctDNA. Among the ctDNA detected, TP53 (56%) is the most common mutations, followed by KRAS (38%), NRAS (13%), PIK3CA (13%), BRAF (6%) and CTNNB1 (6%). Nine of 12 (75%) samples showed complete concordance between ctDNA and mutation detected in tissue samples. In the remaining three samples, additional mutations were detected in plasma samples but not in the matching tissue samples. All six post-treatment samples showed clear decrease in ctDNA allele frequency compared to pre-treatment sample. For samples with more ix62 | abstracts Annals of Oncology than one ctDNA present in the plasma, all detected ctDNAs showed similar extent of decrease after treatment. Plasma ctDNA levels for two patients were followed for at least four months post-treatment. In both cases, changes in ctDNA levels showed a more sensitive and significant alteration compared to image data and CEA levels. Conclusions: Our results indicated that plasma ctDNA can be detected in majority of patients with mCRC. Mutation spectrum detected in plasma is highly concordant with data obtained from tissue samples. The level of ctDNA significantly decrease upon treatment and sensitively reflecting tumor burden. Overall, our results illustrate the clinical feasibility of using ctDNA as a dynamic marker for disease burden in patients with mCRC. Legal entity responsible for the study: Shu-Jen Chen Funding: ACT Genomics Disclosure: All authors have declared no conflicts of interest. 200P Diagnostic accuracy of Raman spectroscopy for malignant and benign colorectal lesions: A meta-analysis Y. Tie Department of Oncology, West China Hospital, Huaxi, Sichuan University, Chengdu, China Background: Raman spectroscopy (RS) is fast, non-invasive, relatively specific, widely available and convenient, which can provide important biochemical macromolecules information including nucleic acids, proteins and lipids based on the inelastic light scattering. RS has been a potential method for colorectal cancer early diagnosis. This work aims to determine, in a meta-analysis for the first time, the diagnostic performance of RS contrast with biopsy in patients with colorectal lesions. Methods: Relevant studies were identified through a comprehensive search of PubMed, Medline, Embase and the Cochrane Library. Studies evaluating the diagnostic performance of RS in patients suspected of having colorectal cancer who underwent RS and biopsy were reviewed. We included studies using biopsy as a reference standard. The pooled weighted sensitivity and specificity were calculated and a summary receiver operating characteristic curve (SROC) was rendered by using Meta-Disc Version 1.4 and STATA 12.0. Further subgroup analysis was conducted in this work. We conducted Deeks ’ funnel plot asymmetry test to investigate publication bias. The quality of the studies was rated with the QUADAS 2. Results: The search strategy produced 113 hits after duplicates removed. Finally, 14 studies were included in this meta-analysis. A total of 1274 patients and 1660 lesions were assessed. Pooled weighted estimates of sensitivity and specificity were 0.87 (95% confidence interval: 0.86 - 0.89) and 0.89 (95% CI: 0.88 - 0.90), respectively. The pooled diagnostic odds ratio of RS in the diagnosis of colorectal cancer was 66.42 (95% CI, 32.90 - 134.08).Symmetric SROC curves showed an overall area under the curve of 0.9578. There was no significant publication bias all around the world (P ¼ 0.34). Conclusions: RS has considerable sensitivity and specificity in the evaluation of colorectal lesions. RS is a promising, reliable method for differential diagnosis of benign and malignant colorectal lesions. Legal entity responsible for the study: Yan Tie Funding: Sichuan University, Chengdu, China Disclosure: All authors have declared no conflicts of interest. 201P POU5F1 gene expression in colorectal cancer: a novel prognostic marker after curative surgical resection N. Miyoshi1, M. Ohue1, M. Yasui1, S. Fujino2, K. Sugimura1, A. Tomokuni1, H. Akita1, S. Kobayashi1, H. Takahashi1, T. Omori1, H. Miyata1, Y. Fujiwara1, M. Yano1 1 Surgery, Osaka Medical Center for Cancer and Cardiovascular Dideases, Osaka, Japan, 2Gastroenterological Surgery, Osaka University, Osaka, Japan Background: POU5F1 (POU domain, class 5, transcription factor 1) also known as OCT-4, expresses in embryonic stem cells, regulating the pluripotency and proliferation. Few studies have examined the expression and significance in cancer tissues, and its significance in colorectal cancer (CRC) is still unknown. Methods: Ninety-five patients with CRC were registered and underwent surgery for resection of CRC and/or distant metastases, if present, at the Osaka Medical Center for Cancer and Cardiovascular Diseases from 2009 to 2011.None of the patients received chemotherapy or radiotherapy prior to surgery. Primary CRC specimens and adjacent normal colorectal mucosa were obtained from patients. Total RNA was prepared and reverse transcription was performed. For quantitative assessment, real-time quantitative reverse transcription (RT)-PCR with Universal Probe Library platform (Roche Diagnostics) was performed using a LightCycler TaqMan Master Kit (Roche Diagnostics) for the cDNA amplification of target specific genes. The expression ratios of POU5F1 mRNA copies in tumor and normal tissues were calculated after normalization against GAPDH mRNA expression. The correlation of gene expression with clinical parameters in patients was assessed. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology Results: Patients with high POU5F1 expression were statistically susceptible to a relatively worse prognosis, and those with low POU5F1 expression showed better disease-free survival than those with high expression. The univariate analysis showed that, lymph node metastasis (p < 0.001), and POU5F1 expression (p ¼ 0.018) were significantly correlated with disease-free survival. The multivariate analysis indicated that POU5F1 high-expression group (hazard ratio, 2.625; 95% confidence interval, 1.054–6.063; p ¼ 0.039) was an independent predictor of disease-free survival, as well as lymph node metastasis. Conclusions: The present data suggests that POU5F1 expression is a prognostic factor in CRC patients. Legal entity responsible for the study: Norikatsi Miyoshi Funding: Osaka Medical Center for Cancer and Cardiovascular Diseases Disclosure: All authors have declared no conflicts of interest. 202P Reactive oxygen species modulator 1 (Romo1) as a prognostic biomarker for colorectal cancer patients who have curative resection H.J. Kim, S.C. Oh Division of Oncology/Hematology, Department of Internal Medicine, Korea University Medical Center, Seoul, Republic of Korea data was studied in 25 patients on the basis of different clinicopathological features. The overall survival was plotted using GraphPad Prism 7 software. Results: The prevalence of KRAS, BRAF, NRAS and PIK3CA mutations was found to be 24%, 6%, 2% and 4% respectively. There was statistically significant association between KRAS mutations with age and tumor differentiation (p < 0.05). In case of BRAF, statistically significant correlation was observed in moderately differentiating (MDA) and poorly differentiating adenocarcinomas (PDA). Overall survival of 37% with median survival of 25 months was observed in case of Indian population, which is much lower in comparison to developed nations. Significant association was observed in survival rate of patients with PDA. In case of localised tumor the median survival was 31 months in comparison to metastatic tumors in which the median survival was 26 months. The survival rate in mutated tumors was found to be 25 months and in wild type, it was 29 months, although statistical significance was not observed. Conclusions: KRAS, BRAF, NRAS and PIK3CA mutations in Indian CRC patients occur at lower levels compared to that in the population of Western developed nations. However, life expectancy has not increased drastically in these years. This study supports the hypothesis that clinical and pathological characteristics are better determinants of prognosis in CRC patients. Legal entity responsible for the study: Reliance Life Sciences Funding: Reliance Life Sciences Disclosure: All authors have declared no conflicts of interest. 204P Background: Reactive oxygen species modulator 1 (Romo1) is a novel protein that plays a crucial role in intracellular reactive oxygen species regulation. In most cancer cell lines, Romo1 is highly expressed and associated with invasiveness and tumor development in vitro. However, its clinical implications in colorectal cancer (CRC) patients are not known well. For the first time, we investigated the association between Romo1 expression and the clinical outcomes of CRC patients who underwent curatively surgical resection. Methods: Romo1 protein expressions in surgically resected tumor tissues were examined immunohistochemically and assessed by histological score. Survival analyses for overall population (n ¼ 208) were performed according to clinical parameters including level of Romo1 expression. The association between Romo1 level and cell invasion was examined using matrigel invasion assay in CRC cell lines. Results: Significantly longer median disease free survival (DFS) was observed in the low Romo1 group compared with the high Romo1 group (160.1 vs 125.1 months, p ¼ 0.012), and the median overall survival (OS) of the low Romo1 group was significantly longer than that of the high Romo1 group (195.4 vs 162.4 months, p ¼ 0.003). Multivariate analyses showed that high Romo1 expression in tumor tissues was significantly associated with short DFS (hazard ratio [HR]¼2.14, 95% confidence interval [CI]: 1.213.78), and with short OS (HR ¼ 3.13, 95% CI:1.377.19). Cell invasion was decreased in Romo1 siRNA transfected CRC cell line in contrast to controlled cell line. Romo1 overexpression in tumor tissue was associated with high lymph node ratio (LNR) between metastatic and examined lymph nodes (p ¼ 0.025). Conclusions: Romo1 overexpression in tumor tissue was significantly associated with poor clinical outcomes in curatively resected CRC patients. Increased Romo1 expression could be a potential adverse prognostic marker. Increased Romo1 level is found to be associated with high LNR. Legal entity responsible for the study: Korea University Medical Center Funding: Korea University Medical Center Disclosure: All authors have declared no conflicts of interest. 203P Molecular analysis of predictive biomarkers-KRAS, BRAF, NRAS and PIK3CA in colon cancer and correlation of clinicopathological features with mutation profiling and therapeutic response in Indian patient cohort H.A. Patil1, S. Gada Saxena1, C. Barrow2, R.K. Kanwar3, J.R. Kanwar3, A. Kapat1 Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt Ltd, Mumbai, India, 2School of Life and Environmental Sciences, Centre for Chemistry and Biotechnology, Deakin University, Melbourne, VIC, Australia, 3 School of Medicine, Centre for Molecular and Medical Research, Faculty of Health, Deakin University, Melbourne, VIC, Australia 1 Background: Colorectal cancer (CRC) is one of the leading causes of cancer mortality worldwide. In this study, the prevalence of KRAS, BRAF, NRAS and PIK3CA mutations was examined in 203 CRC patients from India. The correlation with geographic distribution and clinico-pathological characteristics was studied. We also evaluated the correlation between clinicopathological features and the therapeutic response in 25 Indian CRC cases. Methods: Mutations in KRAS (exon 2, exon 3), BRAF (exon 15), NRAS (exon 2, exon 3) and PIK3CA (exon 9, exon 20) genes were tested using Sanger Sequencing in 203 CRC patients from all over India during the period from January 2013 to July 2016.Treatment Volume 27 | Supplement 9 | December 2016 Attenuated MMR and CIN pathway promote CRC progression through CDC25A upregulation: role of DNMT inhibitors K. Banerjee1, C. Pradhan2, K. Chaudhuri2, A. Mukhopadhyay1, D. Dam1, R. Bhattacharya1 1 Molecular Biology, Netaji Subhas Chandra Bose Cancer Research Institute, Kolkata, India, 2Human Genetics, Indian Institute of Chemical Biology, Kolkata, India Background: Colorectal cancer (CRC) is mainly attributed to CIN (APC) and defective MMR (MLH1, MSH2) pathway genes, although these pathways are not mutually exclusive. Interestingly, CDC25A, the G2/M checkpoint regulator and one of the important targets of both pathways (1, 2) is found to be over expressed in CRC. Thus, aim of our present study was to analyze the RNA and protein expression status of APC, MSH2, MLH1, CDC25A and thus identifying potential CRC biomarkers necessitating therapeutic interventions. Methods: Twenty CRC biopsy specimens and their adjacent normal tissues were taken for the study. Immunohistochemistry to identify the expression of the candidate TSGs of both pathways were carried out following standard protocol. RNA expression analysis for all the candidate genes in tumor and adjacent normal tissues were carried out by qRT-PCR following standard protocol (3). Results: RNA expression analysis of the candidate genes in primary tumor showed overall 60% (n ¼ 20) of the primary tumors to have reduced expression of MMR or APC genes, indicating either genetic or epigenetic alterations of these pathways in those cases (Figure 1). Protein expression analysis showed reduced or no expression of MMR proteins (MLH1, MSH2) in 15% of the tumors. Moderate cytoplasmic and scanty nuclear expression of MMR proteins were observed in 85% of the tumors (Figure 2, 3), indicating their functional attenuation. Majority of the patients showed (80%) high cytoplasmic expression of APC, whereas moderate or low nuclear intensity was found in 10% of patients (Figure 4). Validation of the expression of the candidate genes in HT-29 cells showed, at low concentration (<IC-50), 5Aza-DC (DNMT inhibitor) showed upregulation of the TSGs viz MLH1, MSH2, APC with concomitant down regulation of CDC25A, but not at higher concentration (Figure 5). Conclusions: Expression analysis of the candidate genes in primary tumor showed that the hallmark TSGs of MMR and CIN pathway, viz MLH1, MSH2 and APC respectively, are mostly attenuated in primary CRCs. Synergistic upregulation of TSGs and down regulation of CDC25A in HT-29, at low dose (<IC 50) of 5Aza-DC, indicated dose specific efficiency of DNMT inhibitors in attenuating CRC progression via defective MMR and CIN pathway. Legal entity responsible for the study: N/A Funding: Netaji subhas Chandra Bose Cancer Research Institute Disclosure: All authors have declared no conflicts of interest. 205P Identification of novel bypasses of KRAS addiction S.H. Ly1, E.B. Krall2, W.C. Hahn2 Division of Medical Sciences, Harvard University, Boston, MA, USA, 2 Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA 1 Background: Oncogenic mutations of RAS are detected in approximately 30% of human cancers. KRAS is highly mutated in pancreatic, colorectal and lung cancers. doi:10.1093/annonc/mdw581 | ix63 abstracts Direct therapeutic targeting of Ras and its membrane association has been challenging due to high affinity of GTP to Ras and unexpected mechanism of alternative posttranslational modification. While few inhibitors of downstream RAS effectors – MAPK and PI3K pathways – show some clinical efficacy, they are complicated by complex feedback loops, and as single agents are not effective in KRAS-mutant cancers. Combination therapies may be promising yet limited by narrow therapeutic window. Identification of alternative strategies to directly inhibiting RAS and MAPK/PI3K pathways is key to address this unmet need. Methods: To this end, we performed a genome-scale open reading frames screen to identify genes capable of restoring viability to KRAS-dependent cells (HCT116) following KRAS suppression. One of the top hits included LIM homeobox 9 (LHX9), a homeobox family transcription factor essential for mouse gonad, limb, and brain development. While LHX9 is amplified in several cancers, little is known regarding its roles in cancers. We used hypothesis-driven and unbiased approaches including RNAseq, ChIP-seq, and IP-mass spectrometry to investigate the basis of LHX9-mediated bypass of KRAS dependency. Results: We showed that LHX9 could rescue KRAS suppression in vitro and in vivo. Moreover, LHX9 overexpression in KRAS-dependent cancer cell line was sufficient to form tumors in the absence of KRAS. LHX9 rescued KRAS suppression by at least three mechanisms. First, LHX9 reactivated MAPK and PI3K pathways. Second, LHX9 bound to promoters/enhancers and restored expression of genes including YAP1 which were downregulated by KRAS. Third, LHX9 increased expression and activation of genes including STAT3 whose regulation was independent of KRAS expression. Conclusions: Here, we identified LHX9 as a novel bypass of KRAS addiction. Multiple unbiased approaches revealed at least three mechanisms by which LHX9 rescued KRAS suppression. Our findings contribute to the complex KRAS biology and further investigation may potentially highlight novel therapeutic targets for KRAS-dependent cancers. Legal entity responsible for the study: Harvard University and Dana Farber Cancer Institute Funding: USA National Institutes of Health Disclosure: W.C. Hahn: WCH is a consultant for Novartis and receives grant support from Novartis. All other authors have declared no conflicts of interest. 206P Comprehensive genomic research to clarify the mechanism of drug resistance in colon cancer T. Tanaka, K. Yamashita, S. Ishii, N. Nishizawa, K. Yokoi, H. Katoh, M. Watanabe Surgery, Kitasato University School of Medicine, Sagamihara, Japan Background: Phenylbutyrate (PB) harbors a histone deacetylase antagonist activity that also has anticancer effects and apoptosis. EMT-related genes are associated with PB sensitivity in breast cancer. Methods: 1) We used 6 colorectal cancer cell lines for identification of PB-sensitive and -resistant strains, and added 1-20 fold PB (1fold ¼ 0.5mM). 2) Gene profiles were compared using microarrays (54675 genes) and gene expression were confirmed by PCR. 3) Cells from the PB-resistant strain were treated with the demethylation agent. 4) R 2000) into the PBEMT-rerated genes were elected and transfected (LipofectaminV sensitive strain. Results: 1) Antitumor effect of PB (1fold) was 0% and 45% in PB-resistant (DLD1 and HCT15) and PB-sensitive (HCT116) stains, respectively. 2) 26 genes were elected as PBresistant rerated gene, and their expression were not reduced by demethylation treatment. 3) In 26 genes, ASCL2, LEF1 and TSPAN8 were identified as associated with EMT. 4) PB sensitivity was significantly reduced by the transfection of ASCL2 (p < 0.001), LEF1 (p ¼ 0.006) or TSPAN8 (p < 0.001) into HCT116. Interestingly, the expression of TSPAN8 and LEF1 were induced by transfection of ASCL2, respectively. In siRNA experiments, PB sensitivity was significantly increased by the treatment of the ASCL2 siRNA in PB-resistant strains, and expression of LEF1 and TSPAN8 were reduced with suppression of ASCL2 in HCT15. Conclusions: Anti-tumor effect of PB was found in part of the CRC cell lines. PB sensitivity is likely to be associated with EMT-related genes, however such genes were different according to each cancer type. Genetic controls of a gene expression may largely contributed to EMT change and drug-sensitivity in CRC, while epigenetic controls was associated with them in breast cancer. There is possibility that ASCL2 becomes a new biomarker of drug-sensitivity in CRC. Legal entity responsible for the study: Kitasato University School of Medicine, Surgery Funding: Sanbantyou Gokigen clinic Disclosure: All authors have declared no conflicts of interest. ix64 | abstracts Annals of Oncology 207P Impact of K-RAS mutation status on disease behavior and treatment outcome in metastatic colorectal cancer patients A. Rasmy1;2, A. Fayed3, S. Fouad4 1 Medical Oncology Department, Zagazig University Faculty of Medicine, Zagazig, Egypt, 2Adult Oncology Department, King Fahad Specialist Hospital, Dammam, Saudi Arabia, 3Clinical Oncology Department, Zagazig University, Zagazig, Egypt, 4Internal Medicine Department, Zagazig University, Zagazig, Egypt Background: Over the last 20years, significant improvements have been reported in the treatment outcomes of metastatic colorectal cancer (mCRC).In the molecular-based intervention era, the study of K-RAS mutation status is very important, especially for personalized therapy.Indeed, the median survival of mCRC patients is now approximately 24months(mo.), rather than 12 mo. Methods: This retrospective study analysed the clinical, radiological and laboratory data of 360 mCRC patients(pts) diagnosed at the King Fahad Specialist Hospital Dammam, Saudi Arabia and Zagazig University from Feb. 2011 to Dec. 2015.Chemotherapy primarily included oxaliplatin or irinotecan based combination. Bevacizumab was added for wild-type and mutant K-RAS pts without contraindications, whereas cetuximab was used only for wild-type.Palliative surgery was performed for some obstruction/perforation cases.Treatment response, relapse/progression time and disease-related mortality were evaluated.Limited K-RAS mutation status (exon12,13) was tested for in all pts. The primary aim was to determine the effect of K-RAS mutation status on mCRC disease outcome. Results: Of the 360 pts,65.6% were male and 55% were between age 40–60 years.Wildtype K-RAS was detected in 61.1% pts and mutant K-RAS in 38.9% pts. Most left-sided colon tumours had mutant K-RAS; right-sided colon tumours showed less frequent KRAS mutations(p < 0.000). The majority of mutant K-RAS pts(64.3%) presented with acute obstruction/perforation (p ¼ 0.002). At initial presentation, 62.9% mutant K-RAS pts had liver/lung metastasis. Mean overall disease free survival (DFS) was 10.7mo.Wild-type K-RAS pts had a longer DFS (11.5mo.) than mutant K-RAS pts(9.6 mo.) (p ¼ 0.00).Mean overall survival (OS) was 23.2mo.; however, K-RAS mutation status significantly affected survival time, with 25 mo. for wild-type K-RAS vs. 19.5 mo. for mutant K-RAS (p < 0.001). Disease-related mortality occurred in 132 pts (36.7%), and most (60.6%) had mutant K-RAS (p < 0.001). Conclusions: In mCRC patients, those with the mutant K-RAS form of the disease had an aggressive presentation. Mutant K-RAS patients had poor DFS and OS. Understanding of the factors that regulate K-RAS expression may lead to a new effective therapeutic strategy. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 208P Significance of the difference in size of liver tumors in management of patients with colorectal liver metastases K. Ichida, K. Suzuki, Y. Muto, T. Fukui, Y. Takayama, K. Futsuhara, S. Tsujinaka, Y. Miyakura, H. Noda, T. Rikiyama Surgery, Jichi Medical University Saitama Medical Center, Saitama, Japan Background: The combination of chemotherapy and surgery is currently accepted for the treatment of patients with technically resectable colorectal liver metastases. It is, however, hard to determine which way of chemotherapy or surgery should forward. In this study, we assessed the significance of the difference in size of tumors in pretherapeutic imaging on the selection of chemotherapy in these patients. Methods: We present a retrospective review of 80 consecutive colorectal liver metastases without extrahepatic tumors. The relapse free survival (RFS), the progression free survival (PFS) and overall survival (OS) were assessed and compared between patients with surgery (n ¼ 66) and chemotherapy (n ¼ 14) according to clinical features. Especially, we addressed on pre-therapeutic imaging studies including the distribution and the number of metastatic liver tumors. In addition, the ratio of size in largest to smallest tumor was calculated, two groups classified R < 5 (ratio is less than 5 times) and R 5 (equal or more than 5 times), were compared. Results: Univariate analysis was performed in the surgery group, which revealed that that significant difference in RFS was seen in time of occurrence, the number of tumors and the ratio of tumor diameters. Multivariate analysis showed that the ratio of tumor size, R 5 was the only independent prognostic risk factor in both RFS and OS. We then compared the outcome of patients with prognostic risk factors between surgery and chemotherapy. Surgery gave significantly better OS in those patients than chemotherapy except those with R 5. No difference of OS, in addition to RFS and PFS, was seen in patients with R 5, regardless of treatment. Conclusions: CRC patients with resectable liver metastases harboring R 5 showed no significant difference in outcome by surgery and chemotherapy. Chemotherapy could be an alternative to forward surgery to access oncological concerns such as latent metastases or poor treatment outcome for these patients. Legal entity responsible for the study: Jichi Medical University Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology Funding: Japan Society for the Promotion of Science Disclosure: All authors have declared no conflicts of interest. 209P Efficacy and safety of SOX as an adjuvant therapy for stage 2/ 3 colon cancer in a group at high risk of recurrence in prospective study oxalipatin, reduces the risk of worsening toxicity without compromising long-term efficacy. Legal entity responsible for the study: Olivia Newton-John Cancer Research Institute Funding: N/A Disclosure: All authors have declared no conflicts of interest. 211P H. Osawa Oncology and Hematology, Edogawa Hospital, Tokyo, Japan Risk of selected gastrointestinal and hepatic toxicities in cancer patients treated with nintedanib; a meta-analysis. N. Bahi Eldin1, H. El Halawani1, O. Abdel-Rahman2 Clinical oncology, Ain Shams University Hospital, Cairo, Egypt, 2Oncology, Ain Shams university Faculty of medicine, Cairo, Egypt 1 Background: A number of large scale clinical trials have demonstrated that using a combination of oxaliplatin(L-OHP) and oral-fluoropyrimidines as an adjuvant chemotherapy for stage 2/3 colon cancer improved the prognosis. However, there is no experience in Japanese patients with using SOX therapy, in which S-1 and oxaliplatin are used in combination. Therefore, our objective was to evaluate the efficacy and safety of SOX in Japanese patients as an adjuvant chemotherapy for colon cancer in a single institute prospective study. Methods: The efficacy and safety of SOX as an adjuvant chemotherapy for patients with stage 3 colon cancer and stage 2 patients who had a signature for high risk of recurrence were evaluated in patients who had undergone surgery at our institution between July, 2012 and January, 2015. In principle, the first cycle was given as an in-patient treatment. After the oxaliplatin was dissolved to 130 mg/m2 in 500 ml saline, it was intravenously infused for 120 mins on the first day. S-1, 80mg/m2, was orally administered twice per day, from the evening of day 1 through morning of day 15. The above was, in principle, repeated at 3-week intervals for a total of eight cycles. Results: Thirty-two patients received SOX therapy during the study period: 19 men and 13 women with median age of 65.5 years (32–78 years). Performance status was 0 for 27 patients, and PS 1 for 5 patients. The clinical stages were stage 2 in 5 patients, stage 3A in 19 patients, and stage 3B in 8 patients. The median number of SOX cycles was 8 (2-8 courses). The treatment completion rate was 68.8%. Three-year disease free survival rates were 78.1%. Three-year overall survival rates were 93.8%. In terms of adverse events, the serious adverse events of grade 3 or higher seen among all patients were neutropenia in three patients, thrombocytopenia in two patient, bronchospasm of LOHP in two patients, interstitial pneumonia and diarrhea in one patient and peripheral sensory neuropathy in six patients. However, corneal epithelial disorders, which is characteristic of S-1, was not observed. Conclusions: Efficacy and safety of SOX in Japanese patients as an adjuvant chemotherapy after colon cancer surgery was demonstrated in the latest prospective study report. Legal entity responsible for the study: N/A Funding: IRB of Edogawa Hospital Disclosure: All authors have declared no conflicts of interest. 210P Survival outcomes after toxicity-related dose modification of 5-fluorouracil, leucovorin and oxalipatin (FOLFOX) in stage III, resected colorectal cancer patients F.J. Ha, G. Aksakal, G. Chong Department of Medical Oncology, Olivia Newton-John Cancer Research Institute, Austin Hospital, Melbourne, VIC, Australia Background: FOLFOX is a standard adjuvant chemotherapy regimen in resected stage III colorectal cancer (CRC). Despite established efficacy, toxicity is common and patients often require dose reduction or cessation. The effect of such dose modifications on long-term disease-free survival (DFS) and overall survival (OS) is not known. Methods: We retrospectively assessed outcomes in all patients with stage III, nodepositive, resected CRC diagnosed between January 2005-December 2009 and who received FOLFOX6 adjuvant chemotherapy at a major tertiary hospital. Baseline characteristics, treatment details, toxicity and outcome data were collected from hospital records. Outcome measures included OS, DFS and toxicity. The study was approved by the local institutional review board. Results: 41 eligible patients were identified. Median age was 57 years (IQR 52-67), 49% were female and most patients were ECOG functional status 0-1. Seventy percent completed the intended 12 cycles of FOLFOX. After a median follow-up of 6.3 years (IQR 4.9-7.9), five-year DFS and OS were 73% (95% CI [56-84%]) and 83% (95% CI [65-92%]), respectively. Any-grade toxicities were as follows: gastrointestinal upset, 70%; nausea/ vomiting, 66%; mucositis, 68%; peripheral neuropathy, 98%; and dyspnoea, 24%. No cases of febrile neutropenia were reported. Subsequent to toxicity, 73% had dose reduction or cessation of oxalipatin (median no. of cycles before cessation, 10) and 34% had dose cessation of bolus 5-FU (median no. of cycles before cessation, 5). No significant difference in 5-year DFS or OS was found between patients with usual dosing regimen and those with early reduction/cessation of oxalipatin, bolus 5-FU or both. Conclusions: FOLFOX-associated toxicity is very common in stage III CRC patients, in particular peripheral neuropathy. Despite many patients undergoing subsequent dose limitations, no significant difference in long-term DFS or OS is apparent. Certain dose modifications in FOLFOX, including early cessation of bolus 5-FU and reduction of Volume 27 | Supplement 9 | December 2016 Background: Ameta-analysis of the risk of selected GI and hepatic toxicities associated with nintedanib has been conducted. Methods: Randomized phase II and III trials of cancer patients on nintedanib; describing events of diarrhea, vomiting, elevated alanine aminotransferase (ALT) and elevated aspartate aminotransferase (AST) constituted the eligible studies. Results: After exclusion of ineligible studies, a total of 9 clinical trials were considered eligible for the analysis.The OR for high-grade diarrhea was 3.70 [95% CI: 1.20, 11.48; P ¼ 0.02]; high-grade vomiting: 1.38 [95% CI: 0.76, 2.51; P ¼ 0.28]; high-grade elevated ALT: 6.42 [95% CI: 1.39, 29.78; P ¼ 0.02]; high-grade elevated AST: 7.13 [95% CI: 3.55, 14.29; P < 0.00001]. Conclusions: Analysis of data demonstrated that nintedanib-based regimens are associated with a higher risk of high-grade diarrhea, elevated ALT and elevated AST. Moreover, there is a proportional relationship between nintedanib dose and the risk of elevated transaminases. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 212P Claudin-2: a new regulator of cancer stem cell self-renewal in colorectal cancer S. Paquet-Fifield1, S.L. Koh2, L. Cheng3, L.M. Failla2, F. Hollande2 Pathology, The University of Melbourne, Melbourne, VIC, Australia, 2Pathology, The University of Melburne, Melbourne, VIC, Australia, 3Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, VIC, Australia 1 Background: Colorectal cancer (CRC) represents the third most lethal cancer worldwide. Fatal outcome often results from a recurrence of metastatic tumours, and a subpopulation of cancer cells called Cancer Stem Cells (CSCs) is thought to be instrumental for this process. Although the overexpression of the tight junction protein claudin-2 correlates with cancer progression in human CRC, and its expression in vitro enhances cell proliferation and colony formation and reduces chemosensitivity of CRC cells, the role of claudin-2 in regulating colorectal CSCs remains unknown. Methods: We experimentally overexpressed or down-regulated claudin-2 expression in unique patient-derived cells from primary colorectal tumours and liver metastases, as well as in several classical CRC cell lines, depending on their endogenous level of claudin-2 expression. We performed stem cell assays in vitro (Extreme Limiting Dilution Assay, colonosphere formation assays) and xenograft experiments in vivo to demonstrate that claudin-2 promotes self-renewal of CSCs. We also performed qRT-PCR analysis of stage II/III CRC tumours post-5-FU-based adjuvant chemotherapy, combined with data mining of two large genomic datasets of equivalent samples. Next Generation Sequencing was performed to further analyse miRNAs expression and pathways were analysed. Results: Claudin-2 expression correlates with higher probability of recurrence and poor prognosis in the clinic. Based on the quantification of stem cell activity (ALDH activity), we further show that claudin-2 regulates phenotypic transitions between CSCs and nonCSCs phenotypes. Finally, Next Generation Sequencing analyses comparing levels of miRNAs between the SC-like population expressing or not claudin-2, identified a list of 9 miRNAs directly involved in Wnt/beta-catenin, Stem Cell and Colorectal cancer signalling pathways. Further insights into the molecular regulation of CSCs in CRC by claudin-2 be discussed. Conclusions: Our findings demonstrate for the first time that claudin-2 regulates the self-renewal tumour-initiating ability of colorectal CSCs. These new molecular insights are novel and important to lead the development of future therapeutic strategies targeting CSCs against post-treatment recurrence. Legal entity responsible for the study: University of Melbourne Funding: University of Melbourne Disclosure: S. Paquet-Fifield: The presenter and all co-authors do not identify any financial interest in products or processes involved in their research. S.L. Koh: no financial interest. All other authors have declared no conflicts of interest. doi:10.1093/annonc/mdw581 | ix65 abstracts 213P Prominin-1-targeted apoferritin nanoparticle carrying irinotecan as a novel radiosensitizer for colorectal cancer stem-like cells J.L-Y. Chen1, Y-C. Tsai2, Y-S. Huang2, S-H. Kuo3, M-J. Shieh2 Oncology, National Taiwan University Hospital, Taipei, Taiwan, 2Institute of Biomedical Engineering, Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan, 3Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan Annals of Oncology Legal entity responsible for the study: Park Funding: Park Disclosure: All authors have declared no conflicts of interest. 1 Background: Resistance of cancer stem cells to radiotherapy remains a major obstacle to successful cancer management. Prominin-1 (PROM1) is a marker for cancer stem cells. Nanoparticle (NP) chemotherapeutics have great potential as radiosensitizers. They demonstrate preferential accumulation in tumors and are able to target cancers and cancer stem-like cells through cancer cell-specific molecular ligands, making them uniquely suited for chemoradiation therapy. We aimed to develop a PROM1-targeted NP carrying irinotecan (IRI) and evaluate its utility as a radiosensitizer. Methods: Using a biocompatible apoferritin NP, we engineered a PROM-1 targeted NP (PROM1-NP) carrying IRI. These NPs have sizes of 17.23 60.2 nm and surface charges of -13.5 6 0.2 mV. The synergistic effect of the NPs and irradiation were evaluated in vitro in PROM-1–overexpressing HCT-116 colorectal cancer cell lines using a cell viability assay, and in vivo, in ectopic tumor models using the colony formation assay. Results: PROM1-NPs demonstrated higher intracellular uptake than that of nontargeted NPs or IRI alone. Treatment with PROM1-NPs decreased HCT-116 cell proliferation in a dose- and time-dependent manner. In vitro radiosensitization using irradiation revealed that PROM1-NP was significantly more effective as a radiosensitizer than NP or IRI. The growth of HCT-116 tumor xenografts was markedly slower following treatment with the combination of PROM1-NP plus irradiation than following treatment with NP plus irradiation or IRI plus irradiation, suggesting that PROM1-NP is more effective as a radiosensitizer than IRI or NP in vivo. Conclusions: PROM1-NP is an effective radiosensitizer in PROM-1–overexpressing colorectal cancer cell lines both in vitro and in vivo. Molecular-targeted NPs have great potential as radiosensitizers. Legal entity responsible for the study: National Taiwan University Hospital Funding: Ministry of Science and Technology (MST, Taiwan, under contract of MST 105-2314-B-002-022-) Disclosure: All authors have declared no conflicts of interest. 214P Establishment of colon cancer liver metastasis PDTX model for the evaluation of chemotherapy S. Choi1, J.S. Park1, J. Jung2, D.S. Yoon1 Surgery, Yonsei Cancer Center Yonsei University, Seoul, Republic of Korea, 2 College of Pharmacy, Duksung Women’s University, Seoul, Republic of Korea 1 Background: Colorectal cancer (CRC) often leads to secondary liver metastasis. To predict chemotherapeutic efficacy, an animal model that preserves the physiological properties of patients’ tumors should be established, and this might be achieved using a patient-derived tumor xenograft (PDTX) model that maintain tumor histopathological architecture. The purpose of this study was to characterize the histological and genomic fidelities of CRC-liver metastasis PDTX models and to evaluate the possibility of CRCliver metastasis PDTX models for development of patient tailored chemotherapy. Methods: Tissue obtained from a CRC-liver metastasis patient (F0) was transplanted into a subcutaneous pocket in a non-obese diabetic (NOD)/severe combined immune deficiency (SCID) female mouse (F1). Tumor tissue incubated in NOD/SCID mouse was collected and re-transplanted into nude mice (F2). When tumor volumes reached 500 mm3, F2 mice were randomly divided up into 4 groups (n ¼ 4), that is, a doxorubicin, cisplatin, docetaxel and a non-treated control group. Tumor growths were determined, and tumor tissues were investigated by H&E staining, TUNEL assay, and immunohistochemistry. To determine where mutant allele frequencies vary between different passages, we performed gene mutations in these PDTx and their paired primary tumors by ultra-deep exam sequencing on cancer related genes. Results: Tumorigenesis in the PDTX model (F2) took about 3 weeks. Tumor physiological properties were consistent with those of the patient’s tumors. Anticancer drugs delayed tumor growth, inhibited proliferation, and caused apoptosis. Docetaxel was more effective than the other anticancer drugs. Target exon sequencing analysis showed that there were some genetic variations in 83 cancer related genes across generation. But the prognostic impact of colon cancer mutation profiling EGFR, KRAS, BRAF, PIK3CA, NRAS, APC and TP53 showed the same mutations in paired tumors. This result indicates that mutational changes in PDTX were preserved at lest in the early passages in mice. Conclusions: A CRC liver metastasis PDTX model was established. This model retained the physiological characters of the patient’s tumor and might provide a powerful means for assessing chemotherapeutic efficacy. ix66 | abstracts 215P 53BP1 loss induces the chemoresistance of colorectal cancer cells to 5-fluorouracil by inhibiting ATM-CHK2-P53 pathway H. Ma, J. Yao, A. Huang, T. Zhang Cancer Center, Wuhan Union Hospital (of Tongji Medical College of HUST), Wuhan, China Background: P53 binding protein 1 (53BP1) is a key component in DNA repair to maintain genetic stability and preventing tumors. Our previous study indicated that 53BP1 loss is an adverse prognostic factor of colorectal cancer, but its effect on the sensitivity of colorectal cancer to 5-fluorouracil (5-FU) is unknown. This study aimed to examine the effect of 53BP1 expression on the sensitivity of colorectal cancer to 5-FU. Methods: Immunohistochemical analysis of was performed in 30 metastatic colorectal cancer (mCRC) samples to investigate the association of 53BP1 expression level with clinical therapeutic effect and prognosis. IC50 values for 5-FU and 53BP1 expression were determined by MTT assay and Western blotting in 5 colorectal cancer cell lines. 53BP1 knockdown was also performed in HCT116 and HT29 cells with relatively high 5BP1 expression, and the effects on cell proliferation, apoptosis and cell cycle were evaluated. In addition, the protein expressions of ATM-CHK2-P53 pathway components and Bcl-2 family were measured by Western blotting. Finally, the effect of 53BP1 knockdown on tumor growth and 5-FU chemoresistance was investigated in vivo. Results: 53BP1 expression was closely related to time to progress (TTP) after the firstline chemotherapy based on downregulation of 53BP1 resulting in a reduction of TTP. In vitro, downregulated 53BP1 induced S-phase arrest of HCT116 and HT29 cells, increased the proliferation, inhibited apoptosis after 5-FU treatment, and inhibiting relative proteins expression in ATM-CHK2-P53 apoptotic pathway, as well as apoptotic proteins capase9, capase3 and upregulating Bcl-2 expression. In addition, the in vivo study further confirmed that 53BP1 downregulation accelerated the proliferation of implanted tumor cells in nude mice and enhanced resistance to 5-FU. Conclusions: Our studies showed the 53BP1 loss served as a negative factor to affecting chemotherapy efficacy, and could promote cell proliferation and inhibit apoptosis through inhibition of the pathway of ATM-CHK2-P53 to induce 5-FU resistance. Our study provides a new prospect for the research in this field. Clinical trial indentification: The tumor tissues from 30 mCRC patients who have received first-line chemotherapy were collected from March 2012 to December 2014.The study was approved by the Human Ethics Review Board from the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (Hubei, China). Legal entity responsible for the study: N/A Funding: Supported by Natural Science Foundation of Hubei Province of China, No2015CFB659 Disclosure: All authors have declared no conflicts of interest. 217TiP Dose-finding phase Ib study of FOLFOXIRI plus ramucirumab as first-line therapy for patients with metastatic colorectal cancer K. Yamazaki1, Y. Kito1, T. Esaki2, H. Satake3, H. Taniguchi4, T. Tsuda5, T. Denda6, T. Moriwaki7, K. Mori8 1 Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan, 2Department of Gastrointestinal and Medical Oncology, National Kyushu Cancer Center, Fukuoka, Japan, 3Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan, 4Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, 5Division of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan, 6 Gastroenterology, Chiba Cancer Center Hospital, Chiba, Japan, 7Faculty of Medicine, Division of Gastroenterology, University of Tsukuba, Tsukuba, Japan, 8 Clinical Research Promotion Unit of Clinical Research Center, Shizuoka Cancer Center, Shizuoka, Japan Background: The phase III TRIBE trial which compared FOLFOXIRI plus bevacizumab (Bmab) with FOLFIRI plus Bmab as first-line (1L) therapy (Tx) in pts with metastatic colorectal cancer (mCRC), recently demonstrated that the intensification of the chemotherapy backbone improved progression-free survival (PFS), overall response rate (ORR) and overall survival (OS), and increased the incidence of some adverse events. The phase III RAISE trial has shown the survival benefit of ramucirumab (Rmab) plus FOLFIRI compared with placebo plus FOLFIRI in patients (pts) who progressed during or after 1L Tx with Bmab, oxaliplatin (OX) and fluoropyrimidine. Rmab, an anti-VEGFR-2 monoclonal antibody, prevents ligands (not only VEGF-A, but Volume 27 | Supplement 9 | December 2016 Annals of Oncology also VEGF-C and D) binding and inhibits angiogenesis, although Bmab binds to and blocks circulating VEGF, especially VEGF-A. Therefore, Rmab may clinically inhibit angiogenesis more strongly than Bmab. This phase Ib study aims to determine recommended dose of phase II study. Trial design: Eligibility criteria include histologically confirmed unresectable colorectal adenocarcinoma, age of 20-75 years, ECOG PS of 0–1 (PS of 0 if age of 71–75 years), without homozygous UGT1A1 *28 or *6, no history of prior chemotherapy, and adequate organ function. The primary endpoint is incidence of the dose-limiting toxicity (DLT) of FOLFOXIRI plus Rmab and the main secondary endpoints are ORR, PFS, OS and safety. Three dose levels of FOLFOXIRI plus Rmab are planned as follows; OX dose was fixed at 85 mg/m2. Level 1: 5-fluorouracil (5-FU) 3200mg/m2, irinotecan (IRI) 165mg/m2 and Rmab 8mg/kg, Level 0 as starting dose: 5-FU 2400mg/m2, IRI 150mg/m2 and Rmab 8mg/kg, and Level -1: 5-FU 2400mg/m2, IRI 120mg/m2 and Rmab 8mg/kg. Patients undergo a 3 þ 3 design schema to evaluate the DLT. The recommended dose is defined as the highest dose level where no more than 2 of 6 patients experience a DLT during the first cycle. Seven institutions are participating in this study. This study is registered to the University Hospital Medical Information Network, number UMIN000023277, and activated in July 2016. Clinical trial indentification: The University Hospital Medical Information Network, number UMIN000023277 Legal entity responsible for the study: Shizuoka Cancer Center Funding: Shizuoka Cancer Center Disclosure: K. Yamazaki: Lecture fee from Chugai, Takeda, Taiho, Yakult, DaiichiSankyo, Merck serono, Bristol, Eli Lilly. All other authors have declared no conflicts of interest. 218TiP A phase Ib study of irinotecan, bevacizumab and biweekly TAS-102 in Japanese patients with metastatic colorectal cancer refractory to fluoropyrimidine and oxaliplation (MODURATE) abstracts significantly improved overall survival compared with placebo for refractory metastatic colorectal cancer. Preclinical studies showed TAS-102 additively enhanced the anticancer effect of irinotecan (CPT-11), and the phase I study of TAS-102 administrated on days 1-5 and 8-12 of a 28-day cycle with a fixed dosage of CPT-11 (150 mg/m2) every 2 weeks in Japanese patients demonstrated that the maximum tolerated dose (MTD) of TAS-102 was 30 mg/m2/BID. This combination therapy showed the expected antitumor activity, although the relative dose intensity of CPT-11 was low due to hematological toxicities. Now, we conduct a phase Ib study of biweekly TAS-102 (day 1-5 of a 14-days cycle) with CPT-11 and bevacizumab every 2 weeks. Trial design: The study is conducted in 2 parts: a dose-escalation part (part 1) to determine the MTD and an expansion part (part 2) to further evaluate the safety and preliminary efficacy. Eligibility criteria include histologically proven colorectal adenocarcinoma, failure to first-line chemotherapy with fluoropyrimidine and oxaliplatin, age of 20-75 years, ECOG PS of 0–1, and adequate organ function. The primary endpoint of part 1 is incidence of the dose-limiting toxicity (DLT) of TAS-102, CPT-11 and bevacizumab (5 mg/kg), and that of part 2 is incidence of febrile neutropenia (FN). DLTs include prolonged (> 7 days) grade 4 neutropenia and FN. Five dose levels of TAS-102 and CPT-11 are planned as follows; Level 1: TAS-102 25 mg/m2/BID CPT-11 180 mg/m2, Level 2a: TAS-102 30 mg/m2/BID CPT-11 180 mg/ m2, Level 3a: TAS-102 35 mg/m2/BID CPT-11 180 mg/m2, Level 2b: TAS-102 30 mg/ m2/BID CPT-11 150 mg/m2, Level 3b: TAS-102 35 mg/m2/BID CPT-11 150 mg/m2. In part 1, patients undergo a 3 þ 3 design schema to evaluate the DLT. The recommended dose is defined as the highest dose level where no more than 2 of 6 patients experience a DLT during 2 cycles. Clinical trial indentification: This study is registered to the University Hospital Medical Information Network (UMIN000019828), and activated in August 2016. Legal entity responsible for the study: Shizuoka Cancer Center and Aichi Cancer Center Hospital Funding: Taiho Pharma Disclosure: H. Taniguchi, K. Muro: honoraria by Taiho Pharma. K. Yamazaki: honoraria and research funding by Taiho Pharma. All other authors have declared no conflicts of interest. H. Taniguchi1, Y. Narita1, S. Kadowaki1, T. Ura1, M. Ando1, K. Muro1, S. Hamauchi2, T. Tsushima2, T. Yokota2, A. Todaka2, N. Machida2, A. Fukutomi2, Y. Onozawa2, H. Yasui2, K. Mori3, K. Yamazaki2 1 Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, 2Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan, 3Clinical Research Center, Shizuoka Cancer Center, Shizuoka, Japan Background: The phase III RECOURSE trial demonstrated that TAS-102, an oral fixed-combination drug consisting of trifluridine and tipiracil hydrochloride, Volume 27 | Supplement 9 | December 2016 doi:10.1093/annonc/mdw581 | ix67 Annals of Oncology 27 (Supplement 9): ix68–ix85, 2016 doi:10.1093/annonc/mdw582 Gastrointestinal tumours, non-colorectal 219O Safety and preliminary efficacy of nivolumab in patients with advanced hepatocellular carcinoma: interim analysis of the phase 1/2 CheckMate-040 study abstracts I. Melero1, B. Sangro1, T. Yau2, C. Hsu3, M. Kudo4, T. Crocenzi5, T-Y. Kim6, S.P. Choo7, J. Trojan8, T. Meyer9, T.H. Welling III10, W. Yeo2, A. Chopra11, J. Anderson12, C. Dela Cruz12, L. Lang12, J. Neely12, A. El-Khoueiry13 1 Department of Medical Oncology, Clinica Universidad de Navarra and CIBERehd, Pamplona, Spain, 2Department of Medicine, The University of Hong Kong, Hong Kong, China, 3Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan, 4 Oncology, Kinki University School of Medicine, Osaka, Japan, 5Department of Medical Oncology, Providence Cancer Center, Portland, OR, USA, 6Internal Medicine, Seoul National University Hospital (SNUH)-Yongon Campus, Seoul, Republic of Korea, 7Medical Oncology, National Cancer Center, Singapore, 8 Internal Medicine, Universit€ atsklinikum Frankfurt(Johannes-Wolfgang Goethe Institute), Frankfurt Am Main, Germany, 9Medical Oncology, Royal Free 10 Hospital, London, UK, Surgery, Section of Transplant Surgery, University of Michigan, Ann Arbor, MI, USA, 11Medical Oncology, Johns Hopkins Singapore International Medical Center, Singapore, 12Oncology, Bristol-Myers Squibb, Princeton, NJ, USA, 13Clinical Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA Background: Median overall survival (OS) for first-line (1L) treatment of advanced hepatocellular carcinoma (aHCC) with sorafenib (sor) is up to 11 mo and 7–8 mo with best supportive care (BSC) post-sor failure. Nivolumab (nivo), an IgG4 mAb to the ORR, n (%) (95% CI) CR, n (%) PR, n (%) SD, n (%) PD, n (%) Not evaluable Median DOR, mo (95% CI) Median OS (95% CI) OS rate (all) OS rate, % (95% CI) 6 mo 9 mo 12 mo Sor naı̈ve/intol OS rate, % (95% CI) 6 mo 9 mo 12 mo Sor treated OS rate, % (95% CI) 6 mo 9 mo 12 mo programmed death-1 (PD-1) receptor, was evaluated in a phase 1/2 study of patients (pts) with aHCC. After the multiple ascending-dose escalation (ESC) phase, dose expansion (EXP) followed. Interim results are presented. Methods: Pts had histologically confirmed aHCC, Child-Pugh (CP) scores 7 (ESC) or 6 (EXP). ESC pts who previously failed, refused, or were intolerant (intol) of sor received nivo 0.1–10 mg/kg across 3 cohorts: uninfected HCC, HBV-, and HCVinfected. EXP pts received nivo 3 mg/kg across 4 cohorts: uninfected sor naı̈ve/intol, uninfected sor progressors, HBV-, and HCV-infected. Primary endpoints were safety (ESC) and overall response rate (ORR) by RECIST 1.1 (EXP). Other endpoints included OS, duration of response (DOR), and programmed death-ligand 1 (PD-L1) assessment. Results: 48 (ESC) and 214 (EXP) pts were enrolled and treated with nivo. At baseline, 85% and 70% were CP ¼ 5, 77% and 75% had extrahepatic metastasis, and 73% and 66% had prior sor, for ESC and EXP, respectively. EXP safety profile was similar to that of previously reported ESC. In EXP, treatment-related adverse events (TRAEs) occurred in 65% of pts; 18% of pts had grade 3–4. Most common TRAEs were fatigue (21%), pruritus (15%), rash (12%), and diarrhea (9%); most common grade 3–4 TRAEs were increases in AST (4%), lipase and ALT (3% each), and amylase (2%). Efficacy data are presented in the table. Responses occurred regardless of underlying HCC etiology and PD-L1 expression. Conclusions: Nivo was well tolerated in pts with aHCC. ORR and OS rate for ESC is favorable to historic BSC data. Tolerability and efficacy profiles are consistent between ESC and EXP phases of this ongoing study. Clinical trial indentification: Protocol Number: CA209040 Release Date: May 25, 2012 Legal entity responsible for the study: Bristol-Myers Squibb Funding: Bristol-Myers Squibb Disclosure: I. Melero: Advisory board consulting for BMS, Roche-Genentech, Astrazeneca-medimmune, Boehringer Ingelheim, Alligator, Incyte. B. Sangro: Consulting or Advisory Role - Bayer; Bristol-Myers Squibb; MedImmune Speakers’ Bureau - Bayer; Bristol-Myers Squibb. M. Kudo: Honoraria: Bayer, Eisai, Ajinomoto, Kaken Pharma Consulting/Advisory Role: Taiho, Bayer, BMS, Kowa, Chugai Research Funding: Taiho, Bayer, BMS, Kowa, Chugai, Lilly, Novartis, Pfizer. T. Crocenzi: Table: 219O Efficacy ESC (n 5 48) EXP (n 5 214) 7 (15) (6, 28) 3 (6) 4 (8) 24 (50) 15 (31) 2 (4) 17 (6, 24) 14.3 (9.6, 18.9) 35 (16) (12, 22) 2 (1) 33 (15) 111 (52) 63 (29) 5 (2) Not estimable ___a 66.0 (50.6, 77.6) 66.0 (50.6, 77.6) 59.1 (43.6, 71.7) 82.5 (75.8, 87.5) 70.8 (56.6, 81.1) Not calculatedb n ¼ 11 63.6 (29.7, 84.5) 63.6 (29.7, 84.5) 63.6 (29.7, 84.5) n ¼ 69 88.1 (76.5, 94.2) 72.3 (44.7, 87.7) Not calculatedb n ¼ 37 66.7 (48.9, 79.5) 66.7 (48.9, 79.5) 57.6 (39.7, 71.9) n ¼ 145 80.2 (71.7, 86.5) 71.8 (56.2, 82.6) Not calculatedb CR, complete response; DOR, duration of response; intol, intolerant; ORR, overall response rate; OS, overall survival; PD, progressive disease; PR, partial response; SD, stable disease; Sor, sorafenib a Data not mature; b Not calculated when N at risk is < 5 C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts Annals of Oncology Consulting or Advisory Role - Bristol-Myers Squibb Research Funding - Bristol-Myers Squibb (Inst) Travel, Accommodations, Expenses - Bristol-Myers Squibb. S.P. Choo: advised for and received honorarium from BMS. J. Trojan: BMS:Aadvisory boards and speakers bureau member. W. Yeo: Grants: BMS. A. Chopra: Honoraria: Bayer; Janssen Consulting/Advisory: Astellas Pharma; Bayer; Boehringer Ingelheim; BMS; Lilly; MSD Oncology Research Funding: Eisai Travel/Accommodations, Expenses: Bayer; Boehringer Ingelheim; Merck Serono. J. Anderson, C. Dela Cruz, L. Lang, J. Neely: BMS employee and stockholder. A. El-Khoueiry: Honoraria/Travel Expenses: AstraZeneca, Bayer, BMS, Genentech, GSK Consulting: AstraZeneca, BMS, Genentech/Roche Speakers’ Bureau: Merrimack Research Funding: Astex Pharmaceuticals. All other authors have declared no conflicts of interest. 220O Claudin 18.2 – a novel treatment target in the multicenter, randomized, phase II FAST study, a trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without the antiCLDN18.2 antibody IMAB362 as 1st line therapy in advanced gastric and gastroesophageal junction (GEJ) cancer F. Lordick1, M. Schuler2, S-E. Al-Batran3, Z. Zvirbule4, G. Manikhas5, A. Rusyn6, Y. Vinnyk7, I. Vynnychenko8, N. Fadeeva9, M. Nechaeva10, A. Dudov11, E. Gotovkin12, A. Pecheniy13, I. Bazin14, I. Bondarenko15, B. Melichar16, € Türeci18 C. Huber17, U. Sahin17, O. 1 University Cancer Center Leipzig, University Medicine Leipzig, Leipzig, Germany, 2West German Cancer Center, University Hospital Essen, Essen, Germany, 3Institute of Clinical Cancer Research, Nordwest Hospital, Frankfurt Am Main, Germany, 4Riga East University Hospital, LLC, Riga, Latvia, 5City Clinical Oncology Center, Oncology, St Petersburg, Russian Federation, 6 Zakarpattya Regional Clinical Oncological Center, Department of Chemotherapy, Uzhhorod, Ukraine, 7Kharkiv Regional Clinical Oncology Center, Oncothoracic Department, Sumy State University, Kharkiv, Ukraine, 8Sumy Regional Clinical Oncology Center, Oncothoracic Department, Sumy, Ukraine, 9 Chelyabinsk Regional Clinical Oncology Center, Oncology, Chelyabinsk, Russian Federation, 10Arkhangelsk Clinical Oncology Center, Oncology, Arkhangelsk, Russian Federation, 11University Multiprofile Hospital for Active Treatment “Tsaritsa Yoanna - ISUL”, University Hospital City Clinic Oncology Center, Sofia, Bulgaria, 12Ivanovo Regional Oncology Center, Oncology, Ivanova, Russian Federation, 13Orel Oncology Center, Oncology, Orel, Russian Federation, 14Russian Oncology Research Center n. a. N.N. Blokhin, Oncology, Moscow, Russian Federation, 15Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy, Dnipropetrovsk, Ukraine, 16Palacky University Medical School and Teaching Hospital, Clinic of Oncology, Olomouc, Czech Republic, 17TRON – Translational Oncology at the University Medical Center of the Johannes Gutenberg University, University Mainz, Mainz, Germany, 18Ganymed Pharmaceuticals, AG, Mainz, Germany Background: Claudin(CLDN)18.2 is a stomach specific tight junction protein. The chimeric monoclonal anti-CLDN18.2 antibody IMAB362 potently activates complement and antibody dependent cellular cytotoxicity. FAST investigated CLDN18.2 tumor expression and therapy with IMAB362 in combination with first line chemotherapy in pts with advanced gastric and GEJ cancer. Methods: Pts with advanced gastric and GEJ cancer were centrally evaluated for V CLDN18.2 by immunohistochemistry (CLAUDETECT18.2 Kit). CLDN18.2 expression of 2þ in 40% tumor cells was defined positive. Eligible pts required CLDN18.2þ tumors, an ECOG PS of 0–1, and no medical need for trastuzumab treatment. Pts were randomized 1:1 to first line EOX (epirubicin 50 mg/m2, oxaliplatin 130 mg/m2 d1, and capecitabine 625 mg/m2 bid, d1–21; qd22) with or without IMAB362 (loading dose 800 mg/m2, then 600 mg/m2 d1, qd21). An exploratory 3rd arm was added after arms 1 and 2 had enrolled 80% of pts to test a higher dose of IMAB362 (1000 mg/m2) plus EOX. The primary study endpoint was PFS (arm1 v 2, 70% power, HR 0.72, 1-sided p ¼ 0.1). Results: 686 pts were assessed for CLDN18.2, 334 tumors (48%) were positive per protocol criteria, most with homogenous expression. 161 pts (44% diffuse, 33% intestinal) were randomized into arms 1 and 2, 116 pts had 2þ/3þ CLDN18.2 staining in 70% of tumor cells. IMAB362 plus EOX consistently improved PFS (median 4.8 v 7.9 mon; HR 0.47; 95% CI 0.31–0.70, p ¼ 0.0001), OS (8.4 v 13.2 mon; HR 0.51, 95% CI 0.36–0.73, p ¼ 0.0001) and ORR (28% vs 43%) compared to EOX. Pts with high CLDN18.2 showed stronger effects (PFS HR 0.36; p < 0.0005; OS HR 0.45, p ¼ <0.0005). The exploratory arm 3 also met the primary endpoint (PFS HR 0.59, p ¼ 0.0026). IMAB362-related adverse events included vomiting, neutropenia, and anemia, mostly of NCI-CTC grade 1 or 2. Grade 3/4 events were not significantly increased by IMAB362. Conclusions: CLDN18.2 is a promising novel treatment target for IMAB362 combined with first line chemotherapy in pts with advanced gastric and GEJ cancer. Clinical trial indentification: NCT01630083 Legal entity responsible for the study: Ganymed Pharmaceuticals AG R Volume 27 | Supplement 9 | December 2016 Funding: Ganymed Pharmaceuticals AG Disclosure: F. Lordick: Received research support from GSK and Fresenius Biotech. Lecture and advisory honoraria from Amgen, Biontech, BMS, Eli Lilly, Ganymed, Merck-Serono, Merck-MSD, Nordic and Roche. Travel support Amgen, Bayer, Roche and Taiho. M. Schuler: Research support from Boehringer Ingelheim, BMS, Novartis. Honoraria and Consultation Fees: Alexion, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, IQWig, GSK, Lilly, Novartis, Pfizer. Patents/employment, University Duisburg-Essen. S-E. Al-Batran: has received research support from Merck, Roche, Celgene, Vifor, Medac, Hospira, Lilly. Advisory role: Merck, Roche, Celgene, Lilly, Nordic Pharma. Speaker: Roche, Celgene, Lilly, Nordic Pharma. C. Huber: Stock owner of Ganymed and of BioNTech shares. Member of Ganymed’s and of BioNTechs supervisory board. Scientific advisor of Ganymed, of BioNTech and of TRON. Executive board member of CI3-Cluster. U. Sahin: Stock owner of BioNTech and Ganymed shares. Member of BioNTechs and Ganymed’s supervisory advisory board. Scientific advisor of Ganymed, of BioNTech and of TRON. Patents, BioNTech, TRON, € Türeci: Stock owner of and Ganymed. Employment, BioNTech and of TRON. O. Ganymed and of BioNTech shares. Member of Ganymed’s management board. Scientific advisor of BioNTech and TRON. Employment, Ganymed. Patents, Ganymed, BioNTech and of TRON. All other authors have declared no conflicts of interest. 221PD Efficacy and safety of nanoliposomal irinotecan (nal-IRI, MM-398, PEP02, BAX-2398) in patients with metastatic pancreatic cancer in Asia: A subgroup analysis of the phase 3 NAPOLI-1 Study L-T. Chen1, C-P. Li2, C-F. Chiu3, Y-S. Shan4, J.O. Park5, J-S. Chen6, J.S. Kim7, K-M. Rau8, F. de Jong9, M. Pipas10, B. Belanger11, E. Wang12, K-H. Lee13, Y-J. Bang14 1 Oncology, National Health Research Institutes - National Institute of Cancer Research, Tainan, Taiwan, 2Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, 3Medical Oncology, China Medical University Hospital, Taichung, Taiwan, 4Institute of Clinical Medicine, NCKU, Tainan, Taiwan, 5Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 6Division of Hematology-Oncology, Chang Gung Memorial HospitalLinkou, Taoyuan, Taiwan, 7Oncology, Korea University Guro Hospital, Seoul, Republic of Korea, 8Oncology, Chang Gung Memorial Hospital-Kaohsiung, Kaohsiung, Taiwan, 9Medical Affairs, Oncology, Shire, Baxalta GmbH, Zurich, Switzerland, 10Medicine, Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA, 11Biostatistics, Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA, 12 Drug Development, PharmaEngine, Taipei, Taiwan, 13Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea, 14Medical Oncology, Seoul National University Hospital, Seoul, Republic of Korea Background: The global Phase 3 trial, NAPOLI-1, demonstrated that nal-IRI þ 5fluorouracil and leucovorin (5-FU/LV) significantly improved overall (OS), progression-free survival (PFS) and objective response rate (ORR) vs 5-FU/LV in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPAC) previously treated with gemcitabine-based therapy. Herein, we present a post hoc subgroup analysis of the Asia cohort in the NAPOLI-1 study. Methods: Pts were randomly assigned (1:1:1) to receive nal-IRI (80 mg/m2, equivalent to 70 mg/m2 of irinotecan base) þ 5-FU/LV (2400/400 mg/m2) q2w, nal-IRI (120 mg/ m2, equivalent to 100 mg/m2 of irinotecan base) q3w, or 5-FU/LV (2000/200 mg/m2 weekly for weeks 1-4 q6w). The primary endpoint was OS. Results: Of 132 pts randomized in Asian centers, 34 were assigned to treatment with nal-IRIþ5-FU/LV, 50 with nal-IRI, and 48 with 5-FU/LV. In the Asia cohort, nalIRIþ5-FU/LV significantly improved median OS versus 5-FU/LV (8.9 vs 3.7 months, P ¼ 0.0281) (Table). Improvements in PFS and ORR were also observed. There were no significant differences in outcomes between 5-FU/LV and nal-IRI monotherapy. Grade 3 treatment-emergent adverse events in 15% of pts in either nal-IRI arm were neutropenia (55%, 34%, and 2% in the nal-IRIþ5-FU/LV, nal-IRI, and 5-FU/LV arms, respectively), white blood cell count decreased (21%, 8%, 0%), diarrhea (3%, 16%, 5%), and anemia (18%, 24%, 14%). There were no cases of Grade 3 peripheral neuropathy. Conclusions: This subgroup analysis confirmed that nal-IRIþ5-FU/LV is an efficacious treatment option with a manageable safety profile in patients with mPAC treated in Asia. Nal-IRIþ5-FU/LV may represent a new standard of care for patients with mPAC previously treated with gemcitabine-based therapy. Clinical trial indentification: NCT01494506. Legal entity responsible for the study: Merrimack Funding: Merrimack Disclosure: L-T. Chen: Received data monitoring board, statistician, and support of medical writer from Merirmack, and honorarium from PharmaEngine, Inc. F. de Jong: Employee of and hold stock in Shire. M. Pipas: Employee of and hold stock in Merrimack. B. Belanger: Employee of, hold stock in, and have received reimbursement for travel/accommodations/expenses from Merrimack. E. Wang: Employee of doi:10.1093/annonc/mdw582 | ix69 abstracts Annals of Oncology Table: 221PD Summary of Treatment Efficacy End Point OS, months, median (95% CI) PFS, months, median (95% CI) ORR, % Nal-IRI 1 5-FU/LV (N 5 34) 5-FU/LV Combo Control (N 5 35) HR (95% CI)* 8.9 (4.4, 10.4) 4.0 (1.5, 5.7) 8.8% 3.7 (2.7, 6.4) 1.4 (1.2, 2.0) 0% 0.5087 (0.28, 0.93) 0.4818 (0.27, 0.85) 8.8 (-0.1, 18.4) P value† 0.0281 0.0116 0.1142 Nal-IRI (N 5 50) 5-FU/LV Mono Control (N 5 48) HR (95% CI)* 5.7 (4.8, 7.4) 2.8 (1.5, 4.1) 10.0% 4.3 (3.1, 5.7) 1.4 (1.3, 1.9) 0% 0.8339 (0.53, 1.3) 0.6874 (0.44, 1.1) 10.0 (1.7, 18.3) P value† 0.4263 0.0950 0.0564 *Values reported for ORR represent a difference in proportions rather than a HR, and the CI limits for the difference in ORR are based on normal approximation. † P value is based on Fisher exact test. P values are 2-sided. 223PD PharmaEngine, Inc. The company has the licensing partnership with Merrimack Pharmaceuticals for the product. Y-J. Bang: Consultant for Merrimack. All other authors have declared no conflicts of interest. 222PD Efficacy of consolidation chemotherapy for clinical responder to concurrent chemoradiation in stage II-III squamous cancer of the esophagus Y. Chen1, J. Wang2, X. Cheng3, Q. Wang2, Y. Zhang3, W. Wang2, X. Wu3 Department of Digestive Oncology, Renmin Hospital of Wuhan University, Wuhan, China, 2Department of Radiation Oncology, 4th Hospital Hebei Medical University, Shijiazhuang, China, 3Department of Radiation Oncology, Zhengzhou University Affiliated Cancer Hospital, Henan Cancer Hospital, Zhengzhou, China Neoadjuvant nimotuzumab plus chemoradiotherapy compared to neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy for locally advanced esophageal cancer X. Cheng1, Y. Chen2, X. Wu1, D. Hao1, Y. Zhang1, X. Li1 Department of Radiation Oncology, Zhengzhou University Affiliated Cancer Hospital, Henan Cancer Hospital, Zhengzhou, China, 2Department of Digestive Oncology, Renmin Hospital of Wuhan University, Wuhan, China 1 1 Background: Concurrent chemoradiotherapy (CCRT) has become the standard of care in esophageal cancer patients who are not surgical candidates, but the benefit of consolidation chemotherapy is unknown. The aim of this study was to assess whether consolidation chemotherapy improves the outcome in responders after CCRT in patients with stage II-III squamous cancer of the esophagus. Methods: The characteristics of patients treated with CCRT from September 2005 to September 2013 were reviewed, and those who achieved clinical complete response (CR) and partial response (PR) following CCRT were included in this study. Patients who received CCRT alone (observation group) were compared with patients who underwent CCRT followed by consolidation chemotherapy (consolidation group) with regard to overall survival, treatment failure and toxicity. Baseline characteristics were matched using the propensity score matching method. Results: Of 666 patients recruited (234 observation, 432 consolidation), 249 (37.4%) had clinical stage II disease and 417 (62.6%) had stage III disease. Comparisons of the observation and consolidation groups in the matched population (234 patients in each group) showed median recurrence-free survival rates of 33.8 and 28.6 months (hazard ratio [HR], 1.08; 95%CI [confidence interval], 0.84 to 1.37; P ¼ .549), and median overall survival rates of 44.5 and 41.8 months (HR, 1.03; 95%CI, 0.81 to 1.33; P ¼ .788), respectively. For the patients with stage III disease, median OS did not differ between the observation and consolidation groups, the median OS was 35.6 and 33.7 months, respectively, P ¼ .294. Of those with positive lymph nodes, the median OS was 31.2 months in the observation group and 34.9 months in the consolidation group, P ¼ .638. More mild gastrointestinal reactions were noted in patients receiving consolidation chemotherapy. There was no significant difference in local/regional failure (49.1% vs. 45.3%) and distant failure (21.4% vs. 25.2%) between groups. Conclusions: Consolidation chemotherapy did not increase survival or disease control for patients with stage II-III squamous cancer of the esophagus who respond to CCRT. The role of consolidation chemotherapy remains to be defined. Legal entity responsible for the study: Zhengzhou University Funding: Zhengzhou University Disclosure: All authors have declared no conflicts of interest. Background: We present the study in which combining neoadjuvant treatment of nimotuzumab with chemoradiotherapy (Bio-nCRT) is compared with neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) for patients with potentially resectable locally advanced esophageal cancer. Methods: The data of patients with stage II-III squamous cell carcinoma of the thoracic esophagus who underwent neoadjuvant therapy and esophagectomy was reviewed. Patients who underwent nCT were treated with two cycles of paclitaxel 175 mg/m2 day 1 and cisplatin 25 mg/m2 days 1-3 of a 3-week cycle. Concomitant radiotherapy (40Gy in 20 fractions, 5 days/week) was added in the nCRT group. Participants in Bio-nCRT group were treated with the same nCRT regimen and the administration of nimotuzumab at a flat dose of 200 mg weekly on week 1-5. Esophagectomy was performed 4-6 weeks after the end of neoadjuvant therapy. Results: In total, 195 patients received neoadjuvant therapy and 172 (88.2%) completed the entire trimodal therapy. Surgical resection was performed in 94.4% after Bio-nCRT, versus 92.5% after nCRT and 83.5% after nCT (P ¼ 0.026). The R0 resection rate was 100% after Bio-nCRT, 95.9% after nCRT and 92.6% after nCT (P ¼ 0.030). Pathological complete response (pCR) was achieved in 41.2% after Bio-nCRT, versus 32.4% after nCRT and 14.8% after nCT (P ¼ 0.000). Lymph-node metastases were observed in 29.4% in the Bio-nCRT group, versus 21.6% in the nCRT group and 34.6% in the nCT group (P ¼ 0.126; nCRT vs. nCT, P ¼ 0.042). Conclusions: Comparing to neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy results in higher surgical resection rate, pCR rate and a lower frequency of lymph node metastases. Adding nimotuzumab to neoadjuvant chemoradiotherapy is safe and appears to facilitate complete resection and increase the pCR rate. Legal entity responsible for the study: Zhengzhou University Funding: Zhengzhou University Disclosure: All authors have declared no conflicts of interest. 224PD Predictors for recurrence after initial clinical complete response to definitive chemoradiotherapy in esophageal squamous cell carcinoma patients Y.K. Chao1, H-K. Chang2, C.K. Tseng3 Thoracic Surgery, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan, 2 Dept Hematology-Oncology, Chang Gung Memorial Hospital-Taipei, Taipei, Taiwan, 3Deparment of radiation oncology, Chang Gung Memorial HospitalLinkou, Taoyuan, Taiwan 1 Background: Definitive chemoradiotherapy(dCRT) is a curative treatment option for esophageal cancer and could be an alternative to esophagectomy. However, due to lack of effective diagnostic methods for the response evaluation, some patients who actually harbor residual disease after dCRT were falsely diagnosed as clinical complete response(cCR) and eventually exhibit relapse. The purpose of this study was to ix70 | abstracts Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology investigate the pattern, timing and risk factors for recurrence after cCR in esophageal squamous cell carcinoma(ESCC) patients after dCRT. Methods: Patients who had clinical Stage I–III ESCC and achieved cCR after dCRT between 2001 and 2015 were retrospectively analyzed. Factors associated with recurrence were analyzed using univariate and multivariate analyses. Local recurrence(LR) included the primary tumor while regional and distant recurrence was defined as non-local recurrence(non-LR). Results: There were 128 cCR patients with the mean age of 60.2(range: 3683). After a mean follow-up of 42 months, we identified 71(55.5%) recurrences (44 LR and 27 nonLR). LRs occurred significantly earlier then non-LRs.(Mean: 233 days versus 467 days, p ¼ 0.012). More than 90% LR were detected within 2 years compared with 3 years for non-LR. By multivariate analyses, patient age<60(hazard ratio[HR]:2.799; 95% confidence interval[CI]:1.2776.136; p ¼ 0.01) and pretreatment clinical N3 stage(HR:4.404; 95%CI:1.19716.206; p ¼ 0.026) were independent predictors for LR while no predictors were identified for non-LR. Conclusions: More than 50% of patients who achieved cCR after dCRT developed disease recurrence. Variables related to LR were: patient age<60 and pretreatment clinical N3 stage. Patients with high risk LR should be strictly followed with panendoscopy for the first two years to allow timely salvage treatment before disease progression renders them inoperable. Legal entity responsible for the study: N/A Funding: Chang Gung Memorial Hospital, Linkou Disclosure: All authors have declared no conflicts of interest. 225PD HER 2 over-expression in patients with esophageal squamous cell carcinoma: Correlation with response to neoadjuvant chemoradiation and survival M. Joudi Mashhad1, K. Anvari2, M. Silanian Toussi2, S.A. Aledavood3, B. Memar4 Radiotherapy Oncology Department, Mashhad University of Medical SciencesOmid Hospital Cancer Research Center, Mashhad, Iran, 2Radiation Oncology, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran, 3Cancer Research Center, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran, 4 Pathology department, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran 1 Background: This study was conducted to investigate the frequency of HER2 overexpressionin patients with Esophageal Squamous Cell Carcinoma (ESCC) and its correlation with pathologic response in cases undergoing neo-adjuvant chemoradiation and survival Methods: In this cross sectional study, 68 patients with non-metastatic esophageal SCC who had undergone neo-adjuvant chemotherapy containing cisplatin and 5FU in conjunction with radiotherapy (4000 cGy)between years 2007 to 2014 were evaluated. HER2 expression was assessed by Immunohistochemistry (IHC).The results were classified according to the Herceptest criteria (DAKO): negative (0/1þ), potential positive (2þ) and positive (3þ). HER2 score was also calculated for each specimen. Results:: Hercep test was positive in 42.8% of cases, among which 33.8% were 2þ and 8.8% were 3þ. Her2 score was above 100 in 32.8%. Complete pathologic response was observed in 32.3%. There was no significant difference in the rate of complete response between patients with positive and negative HER-2 over-expression (P- value ¼0.71) .There was also no significant correlation between Her2 score among groups with favorable and unfavorable response to chemoradiation (P-value¼ 0.796 and 0.743 respectively). There was no difference in overall survival in Her2 positive and negative groups (3 years survival was 45 and 54 months respectively, P-value¼0.32).Overall survival was significantly reduce in patients with Her2 score above 100 (P-value¼ 0.045) Conclusions: Her2 positive in ESCC had no effect in tumors biologic behaviors and its response to chemoradiation. Although no correlation was observed between Her2 expression and survival, Her2 score above 100 was associated with shorter survival. Legal entity responsible for the study: N/A Funding: This work was extracted from the MSIs radiation oncology thesis and is supported by Research Deputy of Mashhad University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 226P Neoadjuvant chemotherapy in locally advanced gall bladder cancer: A retrospective tertiary care centre experience A. Sahu1, V. Ostwal2, S. Patkar3, B. Chaudhuri3, S. Shrikhande3, M. Goel3, M. Ramadwar4, N. Shetty5 1 Medical Oncology, Homi Bhabha Cancer Hospital & Research Center, Visakhapatnam, India, 2Medical Oncology, Tata Memorial Hospital Centre, Mumbai, India, 3Surgical Oncology, Tata Memorial Hospital Centre, Mumbai, India, 4Pathology, Tata Memorial Hospital Centre, Mumbai, India, 5 Radiodiagnosis, Tata Memorial Hospital Centre, Mumbai, India Background: Only 10% of gall bladder cancers (GBC) present at an early-stage to be considered surgical candidates and for the rest the goal is palliation. Neoadjuvant chemotherapy (NACT) in locally advanced GBC remains an option still to be explored. Methods: This is a retrospective analysis of prospectively maintained data of 93 consecutive locally advanced GBC patients who were offered NACT with 3-4 cycles of Gemicitabine- Platinum based regimens (either oxaliplatin or cisplatin) between January 2013 to December 2015 at Tata Memorial Hospital. Locally advanced was defined as gall bladder (GB) mass invading liver > 2cm, GB mass adherent to pylorus, duodenum, hepatic flexure and pancreas, coeliac/gastrohepatic adenopathy/portocaval and peripancreatic nodes, bile duct invasion or porta hepatis invasion, vascular invasion – hepatic artery or portal vein, doubtful margin status if resection attempted and residual disease after laparoscopic cholecystectomy at an outside centre. The resectability rate and survival outcomes were analysed for these patients. Results: Median age of the cohort was 52 yrs (31 - 72). Male to female ratio was 1:3. Of 93 patients, 85 (91.3%) completed the scheduled number of cycles of NACT while it was stopped in 3 patients (3.2%) due to rapid clinical deterioration and 5 patients defaulted further follow up. The clinical benefit rate was 70.5%. The overall response rate was 50.6%. Thirty three of 93 patients underwent curative resection after NACT with a resection rate of 37.5%. The median follow up duration was 15 months. The median PFS for the whole cohort was 12.8 months with a 2 yr PFS of 30%. The median PFS of patients who underwent resection was 23 months as compared to 6 months of those who were inoperable (1 yr PFS – Resection done Vs inoperable – 76% Vs 20%; p value – 0.0001). The median overall survival was not reached for the whole cohort with 2yr OS of 57%. 2 yr overall survival in patients who underwent surgical resection as compared to those who were inoperable was 80% Vs 31%; p value – 0.0001. Conclusions: NACT gives a potential chance of cure by downstaging the tumor and making it amenable to resection. It is a feasible option with probable survival benefit which needs to be further evaluated in a larger set of patients. Legal entity responsible for the study: Tata Memorial Centre, Mumbai Funding: Tata Memorial Centre Disclosure: All authors have declared no conflicts of interest. 227P Efficacy of conversional radical surgery following upfront docetaxel, oxalipaltin and S1 (DOS) regimen for advanced gastric cancer with a single non-curable factor Y. Wang, Y. Yu, C. Yuehong, Q. Li, J. Hou, Y. Ji, Y. Sun, Z. Shen, F. Liu, N. Zhao, T. Liu Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China Background: Palliative chemotherapy is still the standard of care for incurable advanced gastric cancer. Several retrospective, single institutional studies have shown that the addition of gastrectomy to chemotherapy might improve patient survival among patients with metastatic gastric cancer with a single non-curable factor. We assessed the effectiveness of conversional radical surgery following docetaxel, oxalipaltin and S1 therapy for advanced gastric cancer with a single non-curable factor. Methods: This is a retrospective observational study. Patients with advanced gastric cancer with a single non-curable factor were performed upfront triplet regimen including docetaxel, oxalipaltin and S1. All patients received oral S-1 80 mg/m2 per day (80-120 mg/day total dose depending on the patient’s body surface area as follows: <1.25 m2, 80 mg; 1.25–1.5 m2, 100 mg; and >1.5 m2, 120 mg) on days 1-21 of every 3week cycle, oxlipatin 100 mg/m2 on day 1 of every 3-week cycle and docetaxel 40 mg/ m2 on day 1 of every 3-weeks cycle. Patients were assessed for response every 2 cycles by CT (computed tomography) scan. A multidisciplinary team reassessed resectability of primary site and metastatic site after 4 cycles. After R0 resection, adjuvant chemotherapy with the original regimen was initiated within 42 days of surgery for another 4 cycles and then S1 single agent till one year. Second-line treatment was recommended for the patients who had evidence of disease progress. The primary endpoint was the response rate. Secondary end points included the R0 resection rate, survival and adverse events. Results: From November 2012 to Feb 2016, 45 patients were enrolled. The response rate was 31.1% (14 patients achieve partial response) and disease control rate was 91.1% (27 patients achieved stable disease and 4 patients had progressive disease). After 4 cycles of chemotherapy, 25 patients achieved radical surgery of primary and metastatic site and one patient whose disease progressed received palliative gastrectomy because of bleeding. All the patients achieving partial response received surgery except for one who refused. After a median follow-up of 10 months (range 3.4–45.8 months), 13 patients doi:10.1093/annonc/mdw582 | ix71 abstracts showed disease progression (3 in the surgery group and 10 in the non-surgery group) or relapse, and 7 patients died (2 in the surgery group and 5 in the non-surgery group). Patients in the surgery group had much longer progression-free survival (not reached vs. 7.9 mo, P ¼ 0.000) and overall survival (not reached vs. 17.5 mo, P ¼ 0.035) compared with the non-surgery group. The most common adverse events were gastrointestinal issues and leukocytopenia which were mild and tolerable. Conclusions: For advanced gastric cancer patients with a single non-curable factor, conversional radical surgery of primary and metastasis sites following upfront DOS regimen showed survival benefit and could be a possible treatment strategy. Legal entity responsible for the study: N/A Funding: NSFC (Natural Science Foundation of China); Grant number: 81273187;NSFC (Natural Science Foundation of China); Grant number: 30972551; Disclosure: All authors have declared no conflicts of interest. 228P Significance of para-aortic lymph node dissection for advanced gastric cancer patients following DCS therapy S. Fushida, K. Oyama, J. Kinoshita, I. Ninomiya, T. Ohta Gastroenterological Surgery, Kanazawa University, Kanazawa, Japan Background: Although JCOG0405 revealed preoperative S-1 plus cisplatin chemotherapy followed by surgery was safety and effective, it was not clear for detailed consideration, such as the correlation between the number of metastatic lymph nodes and prognosis. In this study, we demonstrated the significance of para-aortic lymph node dissection (PAND) for advanced gastric cancer patients following DCS therapy. Methods: Between July 2005 and November 2015, we evaluated retrospectively 24 advanced gastric cancer patients with para-aortic lymph node metastasis diagnosed by thin slice helical CT scan, without hematological metastasis or disseminated metastasis (16a2b1: 14, þa: 10). Patients received two or three cycles of preoperative chemotherapy consisting of docetaxel and cisplatin (35mg/m2) on day 1 and 15 and oral S-1 (40mg/m2 twice daily) on day 1-14 every 4weeks. After chemotherapy, gastrectomy with systematic PAND (16a2b1) was performed. The lymph nodes with disappeared cancer cells due to chemotherapy were determined as follows: no evidence of cancer cells by HE staining; lymphoid follicles were disturbed by fibrosis and granulomatous changes. Results: Response rate was 92%, and pathological response rate was 77%. The adverse events related DCS therapy (G3/4) were 38% of neutropenia, 8% of diarrhea and 8% of anorexia. Gastrectomy with PAND required 396 min (median) of operation time and lost 1225 g of blood. Median number of dissected para-aortic lymph node was 13. Surgery related complications were anastomotic leakage in 2, chyle leakage in 2, and pancreas fistula in 1, postoperative bleeding in 1 and SSI in 1. The mean number of residual cancer cells in dissected para-aortic lymph node was 6, in which small lymph nodes without diagnosis as metastasis were contained. Three-years overall survival was 53%. The patients with 3 more than PAN metastasis or with expand lymph node metastasis beyond 16a2b1 showed significantly worse prognosis than patients without them. Conclusions: Although PAND following DCS therapy has underwent safely, this therapy should be only performed in specialized institutions. To improve prognosis, systematic PAND or basin dissection should be recommended rather than pick up dissection. Clinical trial indentification: UMIN000006036 Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. Annals of Oncology 229P A single arm, multicenter, phase II trial of oxaliplatin plus capecitabine in the perioperative treatment of locally advanced gastric adenocarcinoma in combination with D2 gastrectomy (NEO-CLASSIC) L. Tianshu1, Y. Yu1, Y. Sun2, Y. Min3, H. Cao4, L. Yingbin5, Y. Wang1 Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China, 2 Department of general surgery, Zhongshan Hospital, Fudan University, Shanghai, China, 3Department of General Surgery, Shanghai Ruijin Hospital, Shanghai Jiao Tong University, College of Medicine, Shanghai, China, 4 Department of Gastrointestinal Surgery, Shanghai Renji Hospital, Shanghai, China, 5Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 1 Background: Local advanced gastric carcinoma (LAGC) including stage IB, II and III disease is suggested to be potentially cured by R0 resection. Adjuvant chemotherapy such as oxaliplatin plus capecitabine or S1 can increase the overall survival of patients with early stage but not prolong the survival of patients with more progressive, later stage such as stage III gastric cancer. It’s needed to evaluate whether preoperative chemotherapy combined with D2 gastrectomy plus adjuvant chemotherapy can provide longer survival to those patients. In this study, we plan to evaluate the efficacy and safety of neoadjuvant chemotherapy with oxaliplatin plus capecitabine in more progressive LAGC. Methods: This single arm, open-label, multicenter, phase II trial included 54 patients from 4 clinical sites across China. Patients with newly diagnosed gastric adenocarcinoma, clinically diagnosed stage T2-3/NþM0 or T4aNþM0 according to CT/MRI scan, and judged to be resectable at laparoscopy were enrolled. Patients were treated by capecitabine (1000 mg/m2, bid, day 114 every 3 weeks) plus oxaliplatin (130 mg/m2, d1, every 3 weeks) . After receiving 4 cycles of preoperative XELOX, patients without progressive disease were given surgical evaluation and those who were supposed to be curable were given radical D2 gastrectomy; then the patients will receive another 4 cycles of chemotherapy within 8 weeks after resection. The primary endpoint was the response rate (ORR) of neoadjuvant chemotherapy. Secondary end-points included D2 gastrectomy rate, pathological response, 3-year progression free survival (PFS) rate, 5-year overall survival (OS) rate, health-related quality of life (HRQoL) and safety profiles. Results: Recruitment finished in Apr 2016. One patient underwent emergency gastrectomy before the first assessment because of tumor hemorrhage. Total 27 patients developed partial response according to Recist 1.1.The ORR was 50%, which met the prospective primary endpoint. The D2 gastrectomy rate was 87%. Conclusions: These findings suggest that neoadjuvant chemotherapy followed by D2 gastrectomy might be effective in later stage LAGC. Clinical trial indentification: NCT01880632 Legal entity responsible for the study: Tianshu LIu Funding: Shanghai Roche Pharmaceuticals Limited Disclosure: L. Tianshu, Y. Yu, Y. Sun, Y. Min, H. Cao, L. Yingbin: We acknowledge R . All other authors Shanghai Roche Pharmaceuticals Limited for providing XelodaV have declared no conflicts of interest. 230P Selective gastric cancer patients with peritoneal dissemination benefit from palliative gastrectomy after palliative chemotherapy: Results from two high-volume institutions R-C. Nie, S-Q. Yuan, X-J. Chen, Y-B. Chen Department of Gastric and Pancreatic Surgery, Cancer Centre Sun Yat-sen University, Guangzhou, China Background: To explore whether palliative gastrectomy is suitable for gastric cancer patients with peritoneal metastasis after palliative chemotherapy. Methods: A total of 200 patients were diagnosed with gastric adenocarcinoma with peritoneal metastasis and were treated with palliative chemotherapy afterwards between January 2000 and April 2014 at our centers. The clinicopathologic characteristics and clinical outcomes of the patients were analyzed. Results: This study included 34 patients in the gastrectomy group and 166 patients in the non-gastrectomy group. In the gastrectomy group, tumor were smaller (P ¼ 0.025), ascites were less (P ¼ 0.008), peritoneal seeding were less severe (P ¼ 0.005), the period of first chemotherapy was increased (P < 0.001) and the disease control rate (CRþPRþSD) (P < 0.001) was higher. The median overall survival (OS) of the patients in the gastrectomy group was longer than that in the non-gastrectomy group (22.33 versus 9.53m; P < 0.001). Patients receiving more than 8 periods of first-line chemotherapy has a significant longer median OS than those with those who received 58 periods and those with 1-4 periods (24.43 versus 12.53 versus 7.23m; P < 0.001). Subgroup analyses revealed that patients achieving disease control after chemotherapy benefited from gastrectomy (22.33 versus 11.80m; P < 0.001), while patients achieving no disease control did not (12.43 versus 8.67m; P ¼ 0.595). Also, patients receiving 8 periods of first-line chemotherapy (49.10 versus 20.57m; P ¼ 0.005) and 5-8 periods (21.93 versus 12.03m; P < 0.001) benefited from gastrectomy, and patients with 1-4 ix72 | abstracts Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology periods first chemotherapy did not (4.83 versus 7.23m; P ¼ 0.505). In the multivariate survival analysis, palliative gastrectomy (P ¼ 0.020) and chemotherapy (P < 0.001) remained as the good prognostic factors in predicting the overall survival. Conclusions: Palliative gastrectomy can prolong the survival of gastric cancer patients with peritoneal metastasis when patients achieve disease control after chemotherapy. In addition, the period of first-line chemotherapy should be more than 5 periods, particularly more than 8 periods. Legal entity responsible for the study: Run-Cong Nie Funding: National Natural Science Foundation of China (81302144) Disclosure: All authors have declared no conflicts of interest. 231P Nomogram to predict prognosis in thoracic esophageal squamous cell carcinoma after neoadjuvant radiotherapy or chemoradiotherapy W. Deng1, Q. Wang2, Z. Xiao1, L. Tan3, Z. Zhou1, H. Zhang1, D. Chen1, Q. Feng1, J. Liang1, J. He4, S. Gao4, K. Sun4, G. Cheng4, X. Liu4, D. Fang4, Q. Xue4, Y. Mao4, D. Wang4, J. Li4 1 Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China, 2Radiation Oncology, Sichuan Cancer Hospital, Chengdu, China, 3Radiation Oncology, 1st Hospital of Harbin Medical University, Harbin, China, 4Surgical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China on Days 1 and 22; capecitabine 1000mg/M2 from Day 1 to Day 14 and again from Day 22, followed by Radiotherapy by IMRT for a dose of 41.4 Gy/23 fractions alongwith concomitant chemotherapy with cisplatin 30 mg/M2 weekly, capecitabine 625 mg/M2 orally Day 1 to Day 5 for 5 weeks. After completion of chemoradiation patients were reevaluated for resection. If still unresectable, they continued with radiotherapy up to a total dose of 50.4 Gy and then four more chemotherapy . Results: Result of initial 42 patients with minimum follow up of 18 months is being presented. Treatment compliance was in 100% cases. 27/42 patients were adequately down staged for surgery and resection was done for all of them. Pathological complete response was noted in 12/27. Remaining 15/42 patients had partial regression but not to that extent to be considered for radical resection. At the end of therapy 12/15 had CR. 1 year OS was recorded in all 27 resected patients and in 12/15 patients who could not be resected. 1 year, 18 months and 24 months OS (and DFS) data for resected patients were 27/27 (25/27), 26/27 (21/27) and 26/27 (21/27) respectively. Similar data for unresected patients undergoing NACT followed by chemoradiation were 15/15 (13/15), 9/15 (8/15) and 4/15 (3/15). Conclusions: Addition of 2 cycles of induction chemotherapy prior to chemoradiation resulted satisfactory disease control and enabled radical resection in 65% patients. Main advantage of cisplatin þ capecitabine combination was less cost, less toxicity and less hospital stay for chemotherapy. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 233P Background: It is considered not accurate enough to adopt AJCC staging system to evaluate the survival of patients with esophageal squamous cell carcinoma after neoadjuvant radiotherapy or chemoradiotherapy. Our study aims to establish a nomogram for prognosis estimating and instruction about successive treatment. Methods: We retrospectively reviewed 407 patients who diagnosed with thoracic esophageal squamous cell carcinoma (TESCC) and received neoadjuvant radiotherapy or chemoradiotherapy from 1980 to 2014. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) of categorical age, sex, tumor length, treatment response, lymph node status, resection margin, proximal margin length and anastomotic leakage with overall survival (OS) were calculated using Cox proportional hazard model. Then, the nomogram and recursive partitioning analysis (RPA) model were established respectively, total scores according to each variables were calculated and stratified to predict OS respectively. Results: Four hundred and seven patients were followed-up over a median 26.0 months (49.9months for censor cases). The five year OS and disease free survival (DFS) were 36.7%, 36.1% with median survival time 31.0 and 23.0 months respectively. AJCC 2009 staging system did not performance well in distinguishing OS except IIB and IIIA(p ¼ 0.005). Patients were divided into 4 groups according to the total scores based on nomogram (group A: 180; group B: 180-270; group C: 270-340; group D: >340). The 5 year OS was 57.3%, 40.7%, 18.3%, 6.1%, respectively and DFS was 57.4%, 40.8%, 18.3%, 6.0%, each group shows statistically different prognosis. RPA model indicated that lymph node status, proximal margin length and treatment response were the best prognostic factors, but group 2 and 3 in the 4 groups were not statistically significant (p ¼ 0.574). Conclusions: The nomogram is a good predictor for prognosis in patients with TESCC after neoadjuvant radiotherapy or chemoradiotherapy. AJCC cancer staging system does not accurately identify each groups. RPA model is not good as nomogram in this patient group. Although need more studies to confirm, this nomogram indicates further treatment may be applied to the high risk subgroup. Legal entity responsible for the study: Zefen Xiao Funding: N/A Disclosure: All authors have declared no conflicts of interest. 232P Locally advanced esophageal cancer – evaluation of addition of chemotherapy prior to chemoradiation 1 2 1 S. Saha , A.G. Dastidar , P. Chatterjee Radiotherapy, Apollo Gleneagles Hospital, Kolkata, India, 2Radiotherapy, Institute of Post Graduate Medical Education and Research (I.P.G.M.E & R) & S.S.K.M Hospital, Kolkata, India 1 Background: As yet there is no consensus for locally advanced esophageal cancer patients, regarding the best modality of preoperative therapy. The study aims to explore the impact of pre-surgery treatment intensification by adding neoadjuvant chemotherapy prior to concomitant chemoradiotherapy and in addition to use IMRT to find any possible benefit in lowering surgical morbidity. Study end points are local control, achievement of operability, surgical morbidity and overall survival. Methods: This prospective study initiated in October 2013 for squamous cell carcinoma esophagus with T2 to T4a, Nþ, M0 disease (ECOG 2 or less) not amenable to radical surgery. All patients received 2 cycles of upfront chemotherapy with cisplatin 75 mg/M2 Volume 27 | Supplement 9 | December 2016 Intensive neoadjuvant chemotherapy followed by chemoradiation and intraluminal HDR brachytherapy in esophageal cancer F. Samiei1, S. Sarbaz2, N. Samiei3, N. Farzi3, M. Forootan4, S. Babak3, E. Karimzadeh3 1 Institute Cancer, Central Cancer Institute of Imam Khomeini Hospital, Tehran, Iran, 2Radiation Oncology, Novin Research Institute, Tehran, Iran, 3Radiation Oncology, Laleh Hospital, Tehran, Iran, 4Gastroenterology Research Center, Taleghani Hospital, Tehran, Iran Background: Esophageal cancer optimized treatment is under debate. Treatment failure in the majority of patients is local residue or recurrence mean while the systemic failure is important too.so the role of intensified strategy combining neoadjuvant chemotherapy with maximal local therapy(chemoradiation plus intraluminal brachytherapy) would be hopeful. Methods: We proposed to evaluate esophageal cancer patients in response to two treatment approach: A neoadjuvant chemotherapy (NCT) by docetaxel, cisplatin, 5FU B-NCT by DCF followed by CRT and consolidation by intraluminal HDR brachytherapy (BR). Between Sept 2007 and Sept 2011, seventy five non-metastatic patients who were not candidates for surgery. because of technical or medical limitation entered to study.The patients divided 2 groups: Group I:Relative localized disease(T12N1) Group II: Relative advanced disease(T3-T4 any N) In both groups, we used treatment A&B randomly, NCT scheduled for 4 cycle in both groupsfollowed by CRT(external beam 50Gy concurrentlywith 5FU or capecitabine). HDR brachytherapy delivered in 3 weekly sessions.The patients subgroups could summerized: Group I:IA(NCTþCRT), IB(NCTþCRTþBR) Group II:IIA(NCTþCRT), IIB(NCTþCRTþBR) Results: All 75 cases analysed (mean follow up: 32 months). The response rate(RR) and disease free survival (DFS) are shown: Table: 233P Subgroups No of cases RR(%) cases(%) 1 year DFS cases(%) 3 year DFS IA IB IIA IIB Total 17 17 21 20 75 12(70) 14(82) 9(43) 12(60) 47(62) 10(58) 12(70) 7(33) 9(45) 38(50) 7(41) 10(58) 4(19) 6(30) 27(36) Conclusions: Both stages of disease and treatment consolidation by HDR brachytherapy show significant effect on the outcome. We recommend for all patients to receiveNCT and CRT followed by HDR-BR. Legal entity responsible for the study: Emam Khomeini Hospital, Research Institute Cancer Funding: Emam Khomeini Hospital, Research Institute Cancer Disclosure: All authors have declared no conflicts of interest. doi:10.1093/annonc/mdw582 | ix73 abstracts 234P Improved nutritional status and prognosis in patients with malignant gastroduodenal obstruction using Niti-S duodenal stent M. Shimada, H. Iwase, N. Hirashima, N. Ryuge, N. Urata Gastroenterology, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan Background: Niti-S duodenal stent (Century Medical, Inc.) have been used as a modality for the palliative treatment in patients with malignant gastroduodenal obstruction since 2012. We investigated the efficacy, safety, nutritional condition and the prognosis treated with the Niti-S duodenal stent. Methods: We have treated 23 patients with inoperable malignant gastroduodenal obstruction using Niti-S duodenal stents since May 2012. We evaluated the technical or clinical success rate, procedure time, maintained the oral intake period and the nutritional status. Oral intake was assessed by the gastric outlet obstruction scoring system (GOOSS) and the nutritional status was measured by Onodera’s prognostic nutritional index (PNI) before and after treatment. We also investigated the stent patency, complications and the prognosis. Results: There were 15 males and 8 females and average age was 78.2 years old. The primary diseases were 14 gastric cancer, 4 pancreatic cancer, 2 bile duct cancer, 2 duodenal cancer and an ampullary cancer. Fifteen patients had carcinomatous peritonitis. The technical and clinical success rates were 100% and 87%. The average procedure time was 14.8 minutes. Four patients had double stenting with biliary stent. The GOOSS was significantly improved from 0.5 to 2.4 (p<0.001) after the stent placement. The average maintained the oral intake period was 87.6 days and survival time was 95.5 days. The PNI and the mean survival time (MST) was improved in the GOOSS 3 group compared with 2 or less group (PNI: 32.0 vs 22.8, p<0.01, MST: 111.7 days vs 34.2 days, p<0.05). Re-intervention was required in a patient. The major complication was not observed. Conclusions: Niti-S duodenal stent was effective and safe from malignant gastroduodenal obstruction. The patient’s nutritional status and prognosis were improved after the stent placement. Legal entity responsible for the study: Nagoya Medical Center Funding: Nagoya Medical Center Disclosure: All authors have declared no conflicts of interest. 235P Phase 1b study of nimotuzumab in combination with concurrent chemoradiotherapy in Japanese patients with locally advanced esophageal cancer T. Ura1, K. Kato2, W. Koizumi3, S. Iwasa2, C. Katada3, M. Azuma3, S. Ishikura4, Y. Nakao5, H. Onuma6, K. Muro1 1 Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, 2Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan, 3Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, Japan, 4Department of Radiology, Koshigaya Municipal Hospital, Saitama, Japan, 5Pharmacovigilance Department, Daiichi Sankyo Co., Ltd, Tokyo, Japan, 6Oncology Clinical Development Department, Daiichi Sankyo Co., Ltd, Tokyo, Japan Background: Nimotuzumab is a recombinant humanized IgG1 monoclonal antibody directed against EGFR. The synergistic antitumor effect of nimotuzumab with radiotherapy has been demonstrated in patients (pts) with head and neck cancer and glioma. EGFR is highly expressed in esophageal cancer as head and neck cancer, and therefore high efficacy of nimotuzumab for esophageal cancer was expected. This study assessed the safety, tolerability, efficacy, and PK of nimotuzumab in combination with chemoradiotherapy in Japanese pts with esophageal cancer. Methods: Japanese pts with stage II, III (excluding T4), and IV (only with supraclavicular lymph node) esophageal cancer, were enrolled. This was an open-label, dose-escalation study. Pts received nimotuzumab (level 1: 200 mg/week for 25 weeks, or level 2: 400 mg/ week for first 10 weeks and 400 mg biweekly for next 15 weeks), combined with cisplatin (75 mg/m2 on day 1), and fluorouracil (1000 mg/m2 on days 1 to 4) every 4 weeks for 4 cycles. Radiotherapy was administered concurrently at the dose of 50.4 Gy. PK samples and tumor samples for additional biomarker study were also collected. Results: A total of 10 pts were enrolled in level 1 (7 male, 3 female; median age 63 years, all pts were EGFR 3þ and with squamous cell carcinoma). Dose-limiting toxicities were observed in 2 pts (grade 3 infection and renal disorder) in level 1. An Independent Data Monitoring Committee judged it was acceptable to escalate to level 2; however, the sponsor of this study decided not to enroll any pts in level 2 because of a change in their development strategy. The common grade 3 or higher toxicities were lymphopenia (90%), leukopenia (60%), neutropenia (50%), and febrile neutropenia, decreased appetite, hyponatraemia, and radiation esophagitis (30% each). Neither treatment-related death nor grade 3 or higher skin toxicity was observed. Complete response rate was 50% (95% Cl, 16 – 84). Progression-free survival was 423 days (95% CI, 128 - 519). One- and 3-year survival rates were 80% (95% CI, 41 – 95) and 40% (95% CI, 12 - 67), respectively. ix74 | abstracts Annals of Oncology Conclusions: Nimotuzumab in combination with concurrent chemoradiotherapy was tolerable and effective for Japanese pts with esophageal cancer. Clinical trial indentification: This study was registered with JapicCTI-101319, first released on 25 Oct 2010. The trial protocol number is DE766-A-J102. Legal entity responsible for the study: Daiichi Sankyo Co., Ltd Funding: Daiichi Sankyo Co., Ltd Disclosure: T. Ura: Personal financial interests(Speaking):Merck Serono Co., Ltd, Ono Pharmaceutical Co., Ltd and Chugai Pharmaceutical Co., Ltd. K. Kato: Personal financial interests: Eli Lilly Japan. Institutional financial interests: Ono Pharmaceutical, Merckserono, MSD and Shionogi. W. Koizumi: Personal financial interests: Daiichi Sankyo Co., Ltd. S. Iwasa: Personal financial interests:DaiichiSankyo, EliLily JP, Chugai, MerckSerono, Otsuka. Institutional financial interests:DaiichiSankyo, EliLily JP, Chugai, MerckSerono, Ono, Taiho, AstraZeneca, Eisai, Astellas, Takeda, Bayer, Novartis, Yakult, MSD, Otsuka. Y. Nakao, H. Onuma: The employee of Daiichi Sankyo Co., Ltd. K. Muro: Personal financial interests(Speaking): Takeda, Chugai, Taiho, MerckSerono, Yakult and Eli Lilly. All other authors have declared no conflicts of interest. 236P Comparing chemo-radiotherapy with 5-fluorouracil and cisplatin versus thoracoscopic esophagectomy for cStage IIIII esophageal squamous cell carcinoma T. Kashiwada1, Y. Harada1, Y. Yoda2, H. Noshiro2, N. Aragane1, S. Kimura1 Division of Hematology, Respiratory Medicine and Oncology, Saga University Faculty of Medicine-Nabeshima, Saga, Japan, 2Surgery, Saga University Faculty of Medicine-Nabeshima, Saga, Japan 1 Background: Definitive chemoradiotherapy is one of the curative options for resectable esophageal squamous cell carcinoma with organ preservation. In this single-center observational study, we evaluated the efficacy of chemoradiotherapy (CRT) with cisplatin (CDDP) and 5-fluorouracil (5-FU) and thoracoscopic esohagectomy with or without preoperative chemotherapy for cStage II-III esophageal squamous cell carcinoma. Methods: Between April 2009 and December 2012, 85 cStage II-III esophageal squamous cell carcinoma were enrolled in this study. CRT group were CDDP 70 mg/m2 was administered on days 1 and 29, and 5-FU 700 mg/m2/day was administered on days 1–4 and 29–32. Fractionated radiotherapy was performed on days 1–21 and 29–49; a total dose of 60 Gy was delivered at the rate of 2 Gy per fraction. Surgical resection group were performed thoracoscopic esophagectomy with lymphadenectomy (>D2) with or without preoperative chemotherapy.Final analysis was conducted in June 2016. Survival was monitored for 3 years. Results: Overall survival (OS) of cStageIII patients with CRT was shorter than that of patients with thoracoscopic esophagectomy [hazard ratio, HR 0.431, 95% confidence interval, CI, (0.20-0.95)] and disease-free survival (DFS) also tended to be shorter in patients with chemo-radiotherapy [HR 0.606, (0.28-1.32)]. The OS of cStageII patients with CRT was nearly identical to that for patients with thoracoscopic esophagectomy [HR 0.621, (0.24-1.62)] and DFS showed the same tendency [HR 0.578, (0.25-1.34]. Conclusions: Surgical resection was confirmed to offer a superior survival benefit to the StageIII esophageal cancer, but there are several limitations to our study. This study was retrospective and determination factors of patients’ decision between surgery and CRT were may be affected from the therapeutic effect of preoperative chemotherapy, their performance status and surgical complication rate of the facility. Therefore, selection bias cannot be excluded.The optimal balance of risks versus benefits for the thoracoscopic esophagectomy with chemotherapy should probably be assessed more cautiously in the future. Legal entity responsible for the study: Saga University Funding: Saga University Disclosure: All authors have declared no conflicts of interest. 237P Prognostic characteristics of esophageal cancer patients with multiple primary cancers: A retrospective single institution study Y. Baba, K. Kinoshita, H. Sawayama, K. Mima, M. Iwatsuki, Y. Sakamoto, N. Yoshida, H. Baba Deapartment of Gastroenterological Surgery, Kumamoto University, Kumamoto, Japan Background: The incidence of multiple primary cancer in patients with esophageal squamous cell carcinoma (ESCC) is reported to be approximately 20% in Japan. The most well-known cancers are gastric, head and neck, and lung cancers. The presence of multiple primary cancers may be explained by the concept of ‘‘field cancerization,’’ in which exposure of the epithelium of the head and neck, esophagus, and lung to a common carcinogen (e.g., tobacco, alcohol) leads to multiple carcinomas. Clinical and prognostic characteristics of ESCC patients with multiple primary cancers has yet to be Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology elucidated fully. Thus, the presence of multiple primary cancers often complicates physicians’ decision-making in clinical practice. Methods: This retrospective single institution study included 538 consecutive patients who had undergone resection of ESCC. The Cox proportional hazard model was used to compute the hazard ratio (HR) for mortality. Results: 163 patients (30%) had multiple primary cancers (77 patients, metachronous; 86 patients, synchronous) at the time of surgery. Multiple primary cancer were associated with age, performance status, preoperative treatment, histology, clinical tumor stage, surgical procedure, curability, operation time, and postoperative treatment. In addition, there were a significant relationship of multiple primary cancer with alcohol use and Brinkman index (tobacco smoking). Patients with synchronous cancer had significantly shorter overall survival than those without multiple primary cancer (log-rank P ¼ 0.032; univariate HR ¼ 1.53, 95% confidence interval [CI] 1.02– 2.17, P ¼ 0.040; multivariate HR: 1.61; 95% CI: 1.08–2.36; P ¼ 0.020], while patients with metachronous cancer experienced similar prognosis to those without multiple primary cancer. The prognostic effect of synchronous cancer on overall survival was particularly prominent in patients with Stage I esophageal cancer (log-rank p ¼ 0.00017). Conclusions: Multiple primary cancer was associated with brinkman index, supporting the field cancerization—particularly when caused by tobacco smoking. The presence of multiple primary cancer was one of the independent prognostic factors in patients with ESCC. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 238P Efficacy and toxicity of carboplatin/paclitaxel based chemoradiation for localized esophageal cancer M. Qubtia1, Y. Ishaq1, F. Badar2, K. Munnawar1, A.S. Kazmi1 Medical Oncolgy, Shaukat Khanum Memorial Cancer Hospital and Reserch Centre (SKM), Lahore, Pakistan, 2Cancer Registry and Clinical Data Management, Shaukat Khanum Memorial Cancer Hospital and Reserch Centre (SKM), Lahore, Pakistan 1 Background: Tis study was carried out To establish the efficacy and safety of Carboplatin/paclitaxel combination for neoadjuvant and radical treatment of localized non-metastatic esophageal cancer in combination with radiation and surgery. Methods: Retrospective review of case records of patients registered with oesophageal cancer between September 2013 and October 2014, yielded 139 patients who received treatment with carboplatin/paclitaxel based regimen. Out of these 102 patients with non-metastatic disease, who received radical chemoradiation (CRT) were included for toxicity and efficacy analysis, in the form of radiological response rate, R0 resection rate, progression free survival (PFS) and overall survival (OS). Impact of surgery vs. no surgery was assessed on PFS and OS. Results: Males and females were 71(51.1%) and 68(48.9%) respectively, with squamous cell carcinoma being the predominant histology (92%). Majority of patient belonged to T3/4 and N1 stage. Grade III/IV thrombocytopenia, neutropenia, anaemia, febrile neutropenia requiring hospitalisation, non-hematologic toxicities were noted in 13(12.8%), 18(17.7%), 18(17.7%), 1(1%), 1(1%), patients respectively. Complete Radiological response, partial response, Stable disease, progressive disease were seen in 6(5.9%), 51(50%), 23(22.5%) 8(8.7%), respectively. Resection was done in 29 (28.4%). Complete and partial pathological response were seen 19(65.5%), 10 (34.4%), respectively. PFS at 40 and 80 weeks was 90%, 73%, respectively and OS at 80 weeks was 86%. PFS at 40 and 80 weeks was 100% and 90.5%, respectively with resection, while it was 86% and 65%, without resection (P value 0.015). OS at 40 and 80 weeks was 100% (both) with resection, while it was 96% and 79.5% weeks without resection. (P value 0.034). Conclusions: Carboplatin/paclitaxel based CRT is effective with acceptable toxicity profile in treating localised oesophageal cancer as both as Radical CRT and as a part of multimodality therapy. For definitive results long term follow up and prospective analysis are required. Legal entity responsible for the study: Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore, Pakistan Funding: Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore, Pakistan Disclosure: All authors have declared no conflicts of interest. 239P Primary squamous cell carcinoma of the stomach (PSCCS) – A systematic review and meta-analysis A.G. Thottian, B.P. Venkatesulu, S. Chaliyadan, G.K. Rath Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India Background: PSCCS is a rare entity with less than 150 cases reported in the literature. This study was undertaken to identify the demographic profile, patterns of care and survival data in this subset of stomach cancer. Methods: Full length papers of all cases of PSCCS reported and published in English from 1950 to 2016 were independently searched and retrieved by the authors from PUBMED, Google Search and Cochrane Library. Results: 32 studies with N ¼ 91 were found to be eligible for meta-analysis. Eligibility criteria included full length papers, case series and reports, published in English language between 1950 and 2016. Only cases in which no other synchronous malignancy except for PSCCS were included. Median age of the cohort was 65 years (Range 17 – 83). 72 (79.1%) were male and 19 (20.9%) were female. 63 (69.2%) patients were of Asian origin and 28 (30.8%) were of non-Asian origin. The maximum bulk of the tumour was noted in the fundus/cardia of the stomach (n ¼ 28, 35.4%), followed by body, pylorus/antrum and post gastrectomy stump. 20% of the patients were found to be metastatic upfront. 9 (9.9%) patients had identifiable risk factors for development of squamous cell carcinoma like radiation or corrosive injury, gastrectomy or cyclophosphamide intake. Surgery was the sole treatment in n ¼ 27 (33%), adjuvant or neoadjuvant chemotherapy was delivered in n ¼ 24 (29.6%) and palliative treatment in n ¼ 15 (18.5%). Adjuvant or neo adjuvant therapy significantly improved progression free survival (PFS) but not overall survival (OS). The chemotherapy regimen administered was heterogeneous and the most effective regimen could not be identified. OS ranged from 0 to 72 months with median of 12 months. 3 year OS was 43%. Only T stage was found to be a significant factor for OS in univariate analysis (p ¼ 0.029). Conclusions: PSCCS is a rare entity with limited data available on causation or management strategies. Adjuvant or neoadjuvant chemotherapy in addition to surgery improves PFS. Legal entity responsible for the study: AIIMS Funding: AIIMS Disclosure: All authors have declared no conflicts of interest. 240P Surgical outcome of the elderly with gastric cancer S. Kim, M.S. Kim Surgery, Chosun University Hospital, Gwangju, Republic of Korea Background: Owing to increased life expectancy, the number of elderly gastric cancer patients has grown. This study aimed to find the outcome of patients aged 80 years or older with gastric cancer through comparison of the clinicopathological characteristics, surgical outcomes, and oncologic outcomes. Methods: Between January 2006 and December 2013, 478 patients who had a surgery for gastric cancer were evaluated retrospectively. All patients were divided two groups: patients aged < 80 years old (n ¼ 446) vs. patients aged 80 or older (n ¼ 32). Results: There were no significant differences in gender, length of stay, operation time, depth of invasion, nodal metastasis, histologic type and tumor size between the two groups. But significant differences were revealed in ASA score, body mass index, serum albumin level. Postoperative morbidity, mortality and recurrence did not differ between curatively resected patients in the two groups. Conclusions: In very elderly gastric cancer patients, an active treatment including radical gastrectomy seems to be need. Legal entity responsible for the study: Sungsoo Kim Funding: Chosun University Disclosure: All authors have declared no conflicts of interest. 241P NAB-paclitaxel as third-line therapy after failure of gemcitabine and 5-fluorouracil (5-FU) based combinations in advanced gall bladder cancer patients V. Goel1, V. Talwar1, N. Patnaik2, S. Raina1, S. Singh1 Medical Oncology, Rajiv Gandhi Cancer Institute & Research Center, New Delhi, India, 2Pathology, UCMS & GTB hospital, Delhi, India 1 Background: In literature, there is no standard third-line chemotherapy, post gemcitabine and fluracil based chemotherapy regimens, in metastatic gall bladder cancer patients. So we have done this study to assess the efficacy and toxicity profile of single agent nab-paclitaxel as a third line chemotherapy in metastatic gall bladder cancer patients. Volume 27 | Supplement 9 | December 2016 doi:10.1093/annonc/mdw582 | ix75 abstracts Methods: In this prospective observational study, metastatic gall bladder cancer patients with performance status 2, who progressed on two-lines of therapy, were enrolled from May 2012 to july 2016. Single agent nab-paclitaxel (dose 125mg/m2) was administered on Day 1, 8 and 15 in a cycle of 28 days and i.e. until progression or unacceptable toxicity. Response evaluation was done after 2 cycles of chemotherapy. Results: A total of 34 patients were enrolled in this study. The median age of patients was 62 years (31–71 years), of which 20 (58.82%) were males and 14 (41.17%) were females. The median number of cycles could be given were 3.5 (0.5 – 9.6). 20 patients (58.82%) could be given more than 3 cycles of chemotherapy and only 3 patients (8.82%) in this study received more than 6 cycles of chemotherapy. Disease control rate was seen in 24 (70.58%) patients, with complete response in none, partial response in 13 (38.23%), stable disease in 11 (32.35%) and progressive disease in 10 (29.41%) patients. The median progression free survival was 3.12 months. The median overall survival was 4.9 months. The main Grade 3/4 side effects seen were hematological in 32.35% (n ¼ 11). 8 patients (23.52%) had Grade 1/2 peripheral neuropathy. Conclusions: Nab-paclitaxel is an effective and well-tolerated agent as a third-line option in metastatic gall bladder cancer patients. Further studies are required, especially in the Indian subcontinent. Legal entity responsible for the study: N/A Funding: RGCI&RC Disclosure: All authors have declared no conflicts of interest. 242P Effects of nal-IRI (MM-398) 6 5-fluorouracil on quality of life (QoL) of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine based therapy: Results from NAPOLI-1 R. Hubner1, A. Cubillo2, J-F. Blanc3, D. Melisi4, D.D. von Hoff5, A. Wang-Gillam6, L-T. Chen7, C. Becker8, K. Mamlouk9, B. Belanger10, Y. Yang11, F. de Jong12, J.T. Siveke13 1 Medical Oncology, Christie Hospital NHS Foundation Trust, Manchester, UK, 2 START Madrid, Centro Integral Oncologico Clara Campal, Madrid, Spain, 3 Oncology, Hôpital Saint-André, Bordeaux, France, 4Digestive Molecular Oncology, University of Verona, Verona, Italy, 5Medical Oncology, TGen and Honor Health, Phoenix/Scottsdale, AZ, USA, 6Division of Oncology, Washington University in St. Louis, St. Louis, MO, USA, 7Oncology, National Health Research Institutes - National Institute of Cancer Research, Tainan, Taiwan, 8 Market Access, Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA, 9 Medical Affairs, Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA, 10 Biostatistics, Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA, 11 Global HEOR, Oncology, Baxalta Inc., Cambridge, MA, USA, 12Medical Affairs, Oncology, Shire, Baxalta GmbH, Zurich, Switzerland, 13West German Cancer Center, University Hospital Essen, Essen, Germany Background: The randomized phase 3 NAPOLI-1 study showed that nal-IRI þ 5fluorouracil/leucovorin (5-FU/LV) significantly improved overall survival vs 5-FU/LV (6.1 vs 4.2 months; unstratified hazard ratio 0.67; P ¼ 0.012) in patients with mPDAC previously treated with gemcitabine-based therapy (Wang-Gillam et al., Lancet 2016). QoL was a secondary end point of NAPOLI-1. Methods: Patients were to complete the European Organization for Research and Treatment of Cancer quality-of-life core questionnaire (EORTC-QLQ-C30) at baseline, every 6 weeks, and 30 days after follow-up visit. The population analyzed included patients with a baseline and 1 post-baseline assessment. In a responder analysis, patients were classified as improved (10% improvement from baseline score maintained for 6 weeks), worsened (did not meet improvement criteria and died or had 10% worsening from baseline score), or stable (not improved or worsened) for each subscale. Pairwise treatment arm comparisons on response classification were performed for each subscale using Cochran-Mantel-Haenszel testing adjusted for multiplicity with a Benjamini-Hochberg correction. Results: Of 154 evaluable patients in this population, 69% (49/71) of patients in the nalIRI þ 5-FU/LV arm and 53% (44/83) in the 5-FU/LV arm had data at 12 weeks. Median baseline scores for Global Health Status (GHS), Functional and Symptom Scales were similar between arms. The median change in score at 12 weeks was 0 for both treatment arms for GHS and for all Functional and Symptom Scales except for physical functioning and fatigue. The between-arm differences for physical functioning and fatigue were not substantial. Also, there were no significant between-arm differences in the proportion of improved, worsened, or stable patients. Conclusions: In NAPOLI-1, nal-IRI þ 5-FU/LV–treated patients with data through 12 weeks tended to maintain their baseline QoL over the period, and no significant differences versus the 5-FU/LV–treated patients were observed. Study results are limited by the small number of patients and variability in QoL subscale scores. Clinical trial indentification: NCT01494506 Legal entity responsible for the study: Shire Funding: Shire ix76 | abstracts Annals of Oncology Disclosure: J-F. Blanc: Received honoraria from Baxalta. D. Melisi: Served on advisory board for Eli Lilly and received honoraria from Celgene and Roche. D.D. von Hoff: Served as consultant for AlphaMed. A. Wang-Gillam: Received research funding from Newlink, EMD, Pfizer, AstraZeneca, Pricision Biological, BioMed Valley, Halozyme, ChemoCentryx, OncoMed, ADURO, Millennium, Merrimack, Prometheus, and CTI, and served on ad boards for Pfizer and Merrimack. L-T. Chen: Received data monitoring board, statistician, and support of medical writer from Merrimack and honorarium from PharmaEngine, Inc. C. Becker: Employee of Merrimack. K. Mamlouk, B. Belanger: Employee of, own stock in, and have received reimbursement for travel/accommodations/ expenses from Merrimack. Y. Yang: Employee of and hold stock options in Baxalta Inc. F. de Jong: Employee of and own stock in Shire. J.T. Siveke: Served on ad board for Merrimack. All other authors have declared no conflicts of interest. 243P The effects of genomic polymorphisms in one-carbon metabolism pathways on survival of gastric cancer patients received fluorouracil-based adjuvant therapy T. Zhao Department of Oncology Nanjing First Hospital Nanjing Medical University, Nanjing First Hospital, Nanjing, China Background: Objective: 5-fluorouracil (5-FU) is widely used to treat patients with gastric cancer (GC). However, the response rate is quite heterogeneous. The single nucleotide polymorphisms (SNPs) and their interactions of genes in the one-carbon metabolism (OCM) pathway, including Methylenetetrahydrofolate reductase (MTHFR), Methionine synthase reductase (MTRR), Methionine synthase (MTR), and Thymidylate synthase (TS), significantly affect 5-FU metabolism. Methods: In this study, 650 stage II-III patients were recruited from 1998 to 2006. Among them, 251 received 5-FU-based chemotherapy and other 399 patients were untreated. The Cox regression analysis, log-rank tests and Kaplan–Meier plots were adopted in our study. Results: In the chemotherapy cohort, MTRR 66 GA þ GG genotypes decreased the risk of death (HR ¼ 0.657, 95% CI ¼ 0.446-0.967, p ¼ 0.031), however, the protect effect of MTRR 66 GA þ GG disappeared when GC patients simultaneously had MTHFR 677TT þ TC or MTR 2756GG þ GA genotypes (HR ¼ 0.871, 95% CI ¼ 0.443-1.713; HR ¼ 0.761, 95% CI ¼ 0.451-1.287). TS 50 -UTR 2R3R þ 3R3R genotypes also prolonged overall survival of patients treated with 5-FU (HR ¼ 0.498, 95% CI ¼ 0.2590.960, p ¼ 0.032). And this favorable prognosis obviously enhanced when GC patients simultaneously had TS 30 -UTR DD þ DI and TS 50 -UTR 2R3R þ 3R3R genotypes (HR ¼ 0.332, 95% CI ¼ 0.134-0.822, p ¼ 0.046). Conclusions: Our findings showed that the polymorphisms of MTRR 66 A > G and TS 5’-UTR 3R > 2R may be potential prognostic factors for GC patients receiving 5-FUbased regimens. Legal entity responsible for the study: N/A Funding: This work was partly supported by National 973 Basic Research Program of China (Grant No. 2013CB911300), Grants from National Natural Science Foundation of China (Grant No. 81572928) to Dr. Jinfei Chen; Disclosure: All authors have declared no conflicts of interest. 244P NOP14 promotes invasion and metastasis by maintaining mutant p53-induced oncogenic signaling in pancreatic cancer Y. Du1, L. You1, Z. Li1, C. Liu2, Z. Liu1, Y. Zhao1 General Surgery, Peking Union Medical College Hospital, Beijing, China, 2 Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China 1 Background: Mutant p53 (mutp53) proteins accumulate and promote invasion and metastasis in pancreatic ductal adenocarcinoma (PDAC). However, the mechanism underlying the sustained activation of mutp53 oncogenic signaling is currently unclear. Here, we investigate the function of NOP14 in PDAC metastasis by enhancing the mRNA stability of mutp53, thereby leading to blunted microRNA-17-5p/P21 signaling. Methods: NOP14 expression was evaluated in paired PDAC samples by immunohistochemistry analysis. Wound-healing, in vitro transwell and invasion assays were employed to investigate the impact of NOP14 on PDAC cell movement. In vivo invasion assays were conducted on established subcutaneously/orthotopically/ intravenously injected tumor mouse models to examine the function of NOP14 in PDAC metastasis. In addition, the functional targets of NOP14 were identified by RNA sequencing and quantitative real-time PCR analyses. Further, the correlations among NOP14, mutp53, and the related signaling molecules were assessed by RNA stability, chromatin immunoprecipitation, and immunoblotting assays. Results: Increased NOP14 expression was associated with PDAC progression. NOP14 overexpression promoted cell movement, whereas NOP14 inhibition decreased the invasive capacity of PDAC cells. In vivo invasion assays indicated NOP14 as a promoter Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology of PDAC metastasis. Mechanistically, microRNA-17-5p-mediated P21 signaling was validated as a functional target of NOP14, and NOP14 exerted its regulatory function by increasing the mRNA stability of mutp53 in PDAC cells. Conclusions: Our findings define a novel mechanism for understanding the function of NOP14 in PDAC metastasis. Targeting of NOP14 allows for the effective suppression of tumor cell invasion in a manner that is likely to involve mutp53-induced microRNA-17-5p/ p21 signaling, implicating a potential approach for attenuating metastasis in p53 mutant tumors. Legal entity responsible for the study: Yupei Zhao Funding: The National Nature Science Foundation of China Disclosure: All authors have declared no conflicts of interest. 245P SOX15 expression was associated with poor prognosis in patients with esophageal squamous cell carcinoma: An Iranian cohort study conducted over 10 years 1 2 2 3 4 S. Shahidsales , A. Moradi , F. Ghasemi , K. Anvari , S. Ahmadi-Simab , M.M. Forghanifard5, M.T. Boroushaki6, A. Avan2 1 Radiotherapy Oncology, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran, 2Department of Modern Sciences and Technologies, Mashhad University of Medical Sciences, Mashhad, Iran, 3Radiation Oncology, Mashhad University of Medical SciencesOmid Hospital Cancer Research Center, Mashhad, Iran, 4Cancer Research Center, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran, 5Department of Biology, Islamic Azad University, Damghan, Iran, 6Department of Pharmacology and Pharmacological, Mashhad University of Medical Sciences, Mashhad, Iran Background: WNT/B-CATENIN signaling pathway is one of the key dysregulated pathways in esophageal squamous cell carcinoma (ESCC), which has been reported to be modulated by sex-determining region Y-box (SOX) family genes. SOX15 is recently been identified as a novel tumor suppressor in pancreatic cancer with a potential role in modulating Wnt/b-catenin signaling. The aim of current study was to explore, for the first time, the expression pattern of SOX15 in an Iranian patient cohort with ESCC. Methods: Data in computer-based patient records (CPRs) of Mashhad University of Medical Sciences were used to retrieve all ESCC patients, during July 2004 to September 2014, from Khorasan providence, the second big providence of Iran. Based on the available tissue, one hundred and eight patients were recruited for current study. The stained sections were micro-dissected under a microscope, followed by RNA extraction. The expression pattern of Sox15 was evaluated by real time RT-PCR. Demographic and clinical information were compared across genotype using Pearson tests. OS and PFS curves were analyzed according to Kaplan–Meier method, and compared by log-rank and Wilcoxon tests. The significant prognostic variables in the univariate analysis were included in multivariate analyses, using Cox’s proportional hazards model Results: Our data showed that patients with low mRNA expression of SOX15 had statistically significantly shorter survival (eg, mean ¼ 43.5 months, 95% confidence interval [CI] ¼ 4.4 to 52.6; vs mean¼58.1 months, 95% CI ¼ 56.2 to 80.1; P ¼ 0.04, two-sided logrank test), and multivariable analyses confirmed prognostic relevance of this marker in the patient. In particular, SOX15 downregulation was significantly associated with risk of death (hazard ratio, HR ¼ 1.6, 95% confidence interval [CI], 1.2–2.6) in our population. Conclusions: These results define SOX15 as a novel prognostic factor for ESCC. Further functional analysis is warranted to determine its tumor-suppressor role in ESCC Legal entity responsible for the study: N/A Funding: Mashhad University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. 246P The association of plasma soluble major histocompatibility complex class I polypeptide-related sequence A (sMICA) level with the pathological complete response (pCR) in locally advanced esophageal squamous cell carcinoma (ESCC) H-Y. Kuo1, Y-C. Lin2, J-C. Guo3, T-C. Huang3, C-C. Lin3, K-H. Yeh3, A-L. Cheng3, C-H. Hsu3, C-C. Chang2 1 Oncology Division/Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu City, Taiwan, 2Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu City, Taiwan, 3Oncology Department, National Taiwan University Hospital, Taipei, Taiwan Background: MICA is a ligand for the NKG2D receptors expressed on NK cells and certain types of T cells. Under various types of stress, MICA is induced and shed from the cell surface into the circulation generating a soluble form (sMICA). The sMICA level has been reported to be associated with disease progression of several malignancies and its significance in ESCC patients is unknown. Methods: Thirty-one patients with locally advanced ESCC (all AJCC 6th ed. T3N01M0-1a) who had undergone neoadjuvant paclitaxel/cisplatin-based Volume 27 | Supplement 9 | December 2016 chemoradiotherapy (CRT) followed by esophagectomy in a prospective phase II clinical trial (Lin CC et al: J Clin Oncol 2013;31; suppl; abstr 4099) were included. Their plasma sMICA levels were measured by quantitative ELISA before CRT, after CRT, and after surgery, and then correlated with pCR rate and survival outcomes. Results: With a median follow-up of 51.0 months, the median recurrence-free survival (RFS) and overall survival (OS) of these patients was 23.7(95%C.I. 25.1-48.1) and 51.0 (95%C.I. 39.9-61.1) months. The median (range) of baseline, post-CRT and postsurgery sMICA level was 66.5 (26.1-457.5), 65.0 (25.2-534.6) and 66.9 (25.4-377.3) pg/ ml. Patients with low baseline sMICA, defined as less than the median level, had significantly higher pCR rate than those with high baseline sMICA [62.5% (10/16) vs. 20% (3/15), p ¼ 0.017]. The median RFS (33.9 vs. 22.9m, p ¼ 0.811) and OS (51.0 vs. 51.0m, p ¼ 0.827) were not significantly different between patients with low and high baseline sMICA levels. Table: 246P Baseline plasma sMICA level and pCR rate (n ¼ 31) Baseline plasma sMICA All High Low <60 pg/ml pCR rate 41.9% (13/31) 20.0% (3/15) 62.5% (10/16) 90.9% (10/11) Median RFS(m) Median OS(m) 23.7 22.9 33.9 23.7 51.0 51.0 51.0 51.0 Conclusions: In this relatively small cohort, the low plasma sMICA level was associated with an increased pCR rate in locally advanced ESCC treated with neoadjuvant CRT. Further confirmatory studies with a larger patient population are warranted. (The work was supported by the Grant of HCH105-021 and MOST 104-2320-B-007-002) Legal entity responsible for the study: National Taiwan University Hospital and HsinChu Branch, National Tsing Hua University Funding: National Taiwan University Hospital Hsin-Chu Branch, Ministry of Science and Technology Disclosure: All authors have declared no conflicts of interest. 247P Impact of the preoperative neutrophil-to-lymphocyte ratio in the short term outcomes of patients with gastric cancer R. Miyamoto, S. Inagawa, N. Sano, S. Tadano, M. Yamamoto Department of Gastroenterological Surgery, Tsukuba Medical Center Hospital, Tsukuba, Japan Background: Not only experimental evidence but also growing clinical evidence support an association between the systemic inflammatory response and the progression of various malignancies, including gastric cancers, colorectal cancers, lung cancers, demonstrating an inverse correlation with patient survival. The preoperative neutrophil-to-lymphocyte ratio (NLR) is known to be a strong predictor of mortality in patients with gastric cancer. However, the utility of preoperative NLR to predict short term outcomes in gastric cancer patients remains unclear. Therefore, the aim of our study was to determine whether the preoperative NLR is a predictive value of short term outcome in gastric cancer patients. Methods: One hundred resected gastric cancer patients were retrospectively enrolled. Median NLR was calculated, and 2.7 was set as cut-off value. The patients were then divided into two groups: high-NLR group (n ¼ 47) and low-NLR group (n ¼ 53). The patient characteristics and perioperative outcomes were respectively compared between the two groups. In addition to the preoperative NLR, we also employed the Estimation of Physiological Ability and Surgical Stress (E-PASS) scoring system and Glasgow prognostic score (GPS) as a predictor of postoperative complications. Results: Among low-NLR group and high-NLR group, significant differences were respectively observed in perfomance status (0.05 6 0.30, 0.30 6 0.69; p ¼ 0.018), EPASS score (0.20 6 0.25, 0.30 6 0.29; p ¼ 0.121), GPS (0.18 6 0.44, 0.38 6 0.60; p ¼ 0.003), TMN stage (p ¼ 0.001). In terms of postoperative complications, ClavienDindo’s Grade III-V complications [2 (3.7%), 11 (23.4%); p ¼ 0.015], and intraoperative blood loss (151 6 179, 248 6 403; p ¼ 0.022) among low-NLR group and high-NLR group. Conclusions: The present study indicated that the preoperative NLR influenced short term outcomes including postoperative complications and intraoperative blood loss in gastric cancer patients. The preoperative NLR is a useful predictive value of short term outcome in gastric cancer patients. Legal entity responsible for the study: Tsukuba Medical Center Hospital ethics committee approved this study. Funding: N/A Disclosure: All authors have declared no conflicts of interest. doi:10.1093/annonc/mdw582 | ix77 abstracts 248P Substantial RUNX3 expression and co-existence with EZH2 in esophageal cancer: a new finding in Indian esophageal cancer patients A.U. Rehman1, M.A. Iqbal2, S. Saikia3, P.K. Mishra4, S.S. Saluja4, S. Medhi3, S.A. Husain5 1 Biosciences, Jamia Millia Islamia, Delhi, India, 2Department of Biotechnology, Jamia Millia Islamia, Delhi, India, 3Department of Bioengineering and Technology, Gauhati University, Guwahati, India, 4GI Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education & Research, New Delhi, India, 5 Department of Biosciences, Jamia Millia Islamia, Delhi, India Background: Runt related transcription factor3 (RUNX3) is considered as a tumor suppressor gene (TSG) that functions through the TGF-b dependent apoptosis. Hypermethylation of CpG islands of RUNX3 promoter and overexpression of enhancer of zeste homolog 2 (EZH2) has been suggested to downregulate RUNX3 in cancer. Here, we studied the expression of RUNX3 and EZH2 in tumors along with adjacent normal mucosa from 58 esophageal cancer (CaEs) patients of India and its mechanism of downregulation in CaEs. Methods: mRNA level, protein expression and cellular localization of EZH2 and RUNX3 were analyzed using real-time PCR, Western blot and immunohistochemistry, respectively. DNA methylation was also assessed by methylation specific-PCR. Clinicopathological parameters were recorded and correlated with the EZH2 and RUNX3 expression. Results: Out of 58 patients, 89.6% were squamous cell carcinoma and 11.4% were adenocarcinoma. 91.3% patients had locally advanced tumor whereas 8.7% were metastatic. 10.3% patients had upper CaEs, 48.3% had in the middle third and 41.4% had esophageal cancer in the lower third region. Out of 58 CaEs 25(43.1%) patients had stage I or stage II cancer whereas 33 (56.9%) patients had stage III or stage IV cancer. However, none of these parameters were found to be significantly correlated with the RUNX3 or EZH2 expression. Compared to normal mucosa, a significant increase in expression of RUNX3 mRNA in 34/58 patients (p < 0.017) was observed. Out of remaining 24 cases having low RUNX3 mRNA, 20 patients had DNA hypermethylation at the promoter region of the RUNX3 (p < 0.0001). Western blotting of 20 patient samples revealed high protein expression of RUNX3 in 13 patients. The expression of EZH2 was not significantly upregulated compared to normal. However, a significant positive correlation between EZH2 and RUNX3 expression was observed (p < 0.03). Conclusions: The data of this study provide new insights into the biology of RUNX3 and questions our current understanding of the role of RUNX3 in cancer. Legal entity responsible for the study: Department Of Biotechnology (DBT NER BPMC) Funding: Department Of Biotechnoloy (DBT NER BPMC) Disclosure: All authors have declared no conflicts of interest. 249P Galectin-3 promotes cell proliferation and attenuates cytotoxic effect of paclitaxel via ERK signaling pathway in gastric cancer cells N. Serizawa1, A. Nagahara2, S. Yamashina1, Y. Inami1, S. Watanabe1 Gastroenterology, Juntendo University Hospital, Tokyo, Japan, 2 Gastroenterology, Juntendo University Shizuoka Hospital, Shizuoka, Japan 1 Background: Galectin-3 (gal-3), which is a b-galactosidase binding lectin, is highly expressed in gastric cancer cells and modulates cell proliferation. Paclitaxel, which stabilizes the microtubule, has much broader activity such as modulation of mitogenactivated protein kinase (MAPK) signaling pathway. Our aim in this study is to elucidate the mechanism by which gal-3 may contribute to cell proliferation and to assess whether silencing of gal-3 enhances the cytotoxic effect of paclitaxel on gastric cancer cell proliferation via MAPK pathway. Methods: MKN-45 (Human gastric cancer cell) was transfected with gal-3 or scrambled (scr) siRNA, and 48 hours later the following experiments were performed in each condition. Gal-3 expression was by western blotting. After 10 minutes of exposure to Epidermal Growth Factor (EGF), cell proliferation was assessed by CCK-8. Extracellular Signal-regulated Kinase (ERK) phosphorylation was tested as a downstream target by western blotting. Cell proliferation was tested by CCK-8 and ERK phosphorylation was tested by western blotting in the presence or absence of paclitaxel in each condition in order to assess downstream signaling pathway. Results: The number of proliferating cells was significantly lower in gal-3 siRNA transfected cells than those transfected with scr siRNA, suggesting that gal-3 plays a role in gastric cancer cell proliferation. After EGF exposure, phosphorylation of ERK was reduced in gal-3 siRNA transfected cells, indicating that gal-3 is inducing ERK mediated signaling pathway. When paclitaxel was used in combination with gal-3 or scr siRNA transfected cells, proliferating cells were significantly decreased in gal-3 siRNA/ paclitaxel combination compared to scr siRNA/paclitaxel combination, suggesting that silencing gal-3 enhances the paclitaxel effect on gastric cancer cell proliferation. ERK phosphorylation was reduced in gal-3 siRNA/paclitaxel combination compared to scr ix78 | abstracts Annals of Oncology siRNA/paclitaxel combination, indicating that gal-3 attenuates cytotoxic effect of paclitaxel via ERK signaling pathway in gastric cancer cells. Conclusions: Gal-3 promotes cell proliferation and attenuates cytotoxic effect of paclitaxel via ERK signaling pathway. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 250P Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer J. Chen Department of Gastric Cancer and Soft Tissue Sarcomas, Shanghai Cancer Center Fudan University, Shanghai, China Background: Circular RNAs (circRNAs) comprise a novel class of widespread noncoding RNAs that may regulate gene expression in eukaryotes. However, the characterization and function of circRNAs in human cancer remain elusive. The aim of this study was to assess the circRNA profile and to identify the functional and prognostic significance of circRNA in gastric cancer (GC). Methods: Ribosomal-depleted RNA sequencing and a bioinformatic analysis were performed to identify circRNA candidates. The expression of circRNA was examined in paired normal and cancerous gastric tissues. Molecular and cellular techniques were used to explore the biological function and mechanism of circRNA in GC cells. The prognostic significance was analyzed using the Kaplan-Meier method and the Cox proportional hazards model. Results: We identified at least 5500 distinct circRNA candidates and a series of circRNAs that are differentially expressed in GC tissues compared with matched normal tissues. We further characterized one circRNA derived from the PVT1 gene, which was termed circPVT1. The expression of circPVT1 is often upregulated in GC tissues due to the amplification of its genomic locus. circPVT1 may promote cell proliferation by acting as a sponge for members of the miR-125 family. The level of circPVT1 was observed as an independent prognostic marker for overall survival and disease-free survival of patients with GC. Conclusions: Our findings suggest that circPVT1 is a novel proliferative factor and prognostic marker in gastric cancer. Clinical trial indentification: 12/18/2016 Legal entity responsible for the study: N/A Funding: NSFC china Disclosure: All authors have declared no conflicts of interest. 251P Association of Epstein-Barr virus with prognosis of patients with esophageal squamous cell carcinoma: A retrospective cohort study S. Shahidsales1, A. Moradi2, F. Ghasemi3, K. Anvari1, S. Ahmadi-Simab4, M.T. Boroushaki5, A. Avan3 1 Radiation Oncology, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran, 2Department of Biology, Islamic Azad University, Damghan, Iran, 3Department of Modern Sciences and Technologies, Mashhad University of Medical Sciences, Mashhad, Iran, 4Cancer Research Center, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran, 5Department of Pharmacology and Pharmacological, Mashhad University of Medical Sciences, Mashhad, Iran Background: Esophageal squamous cell carcinoma (ESCC) is among the leading cause of cancer related death within gastrointestinal tumors. There is growing body of evidence showing the association of Epstein Barr Virus (EBV) infection with the development of malignancies including B-cell non-Hodgkin lymphoma, Hodgkin disease and Burkett lymphoma, although its potential association with ESCC is still controversial. Therefore in the present study we explored the association of EBV with pathological information and clinical outcome of 108 ESCC patients. Methods: This retrospective cohort study included 141 cases of ESCC identified at Omid hospital of Mashhad University of Medical Science between July 2005 to September 2014. The ESCC tissue was stained with H&E, follow by DNA extraction. The present of EBV was evaluated using an Epstein-Barr virus PCR detection Kit. Univariate/multivariate analyses were employed to investigate the association of EBV with overall survival and progression free survival. Results: Among the patients, 48% of patients were female, and 52% were male with mean age of 59.2611.1yr. 5.6%, 21.3%, and 71.3% of patients were T1, T2, T3, respectively, while 32.4% of patients had lymph node metastases. In order to explore whether patient characteristics might influence clinical outcome, we analyzed data on PFS and OS according to patients’ clinicopathological features. Tumor size, node and metastasis status, and stage were associated with shorter OS and PFS. Of note we observed the present of EBV in 6.5% patients, and 100% of EBV infected patients were Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology at T2 and T3, while 42.8% of these patients had lymph node positive. EBV positive patients were associated with more advanced stages Conclusions: our findings demonstrate the presence of EBV in 6.5% of Iranian patients and its potential link with tumor size, supporting further studies in multi-center setting to determine its association with development and progression of ESCC Legal entity responsible for the study: N/A Funding: Mashhad University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. 252P Expression of Ribophorine II (RPN2) is a new prognostic factor in human gastric adenocarcinoma. D. Fujimoto, T. Goi, H. Kurebayashi, S. Kato, M. Morikawa, K. Koneri, M. Murakami, Y. Hirono Department of First Surgery, University of Fukui Hospital, Fukui, Japan Background: The increased invasiveness of gastric adenocarcinoma is important for progression and metastasis. In recent molecular biological studies, Ribophorine II(RPN2) induces epithelial-mesenchymal transition and metastatic activity in highly metastatic breast cancer cells. However, no studies have evaluated the relationship between RPN2 expression, ability of cancer to invade/metastasis, and patient prognosis in gastric adenocarcinoma. Accordingly, we have examined these factors. Methods: Immunohistochemical staining was performed to detect RPN2 in the primary lesion and adjacent normal gastric mucosa of 242 gastric adenocarcinoma patients who underwent resection surgery. Additionally, we conducted clinicopathologic examinations and analyzed patient prognoses with the Kaplan-Meier method. Further, multivariate analysis was conducted using a cox-hazard model. Results: RPN2 expression was observed in 119 of 242 cases of gastric adenocarcinoma patients. RPN2 expression was associated with a higher incidence of depth of wall invasion, lymphnode metastasis, lymphatic invasion, venous invasion, peritoneal dissemination, and histopathological stage. In Stage II and III curative resection cases, where recurrence is the most serious problem, cases that expressed RPN2 had a significantly lower 5-year survival rate and higher recurrence rate compared to these cases with no RPN2 expression. In the multivariate analysis for prognosis, RPN2 expression was found to be an independent factor. Conclusions: RPN2 expression correlates with gastric adenocarcinoma cell invasion and could be one of the new prognostic factors in human gastric adenocarcinoma. Legal entity responsible for the study: N/A Funding: JSPS KAKENHI Grant number 26861065 Disclosure: All authors have declared no conflicts of interest. 253P The role of MiR-221 in regulating gastric cancer radiation sensitivity G. Li, Y. Deng, L. Liang Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China Background: The purpose of this study was to define the roles of miR-221 in determining sensitivity of gastric cancer to radiation therapy, to explore the underlying mechanism and to evaluate the potential of miR-221 as a biomarker for predicting radio-sensitivity. Methods: Tumor specimens from 8 patients with a histological diagnosis of gastric adenocarcinoma (stage IIIB/IIIC) which was unrescectable under original evaluation were used in the micro-RNA profiling and comparison. And these specimens were from our phase II study (NCT02024217). These patients never received any chemotherapy before radiation therapy. Human gastric cancer cell lines, MGC-803 and MKN28, were used in vitro (cell culture) studies. Transfection of tumor cells with the mimic or inhibitor of miR-221, and reporter gene assay, were performed to investigate the role of miR-221 in determining radio-sensitivity and the target gene. Results: Higher expression of miR-221 was observed in human gastric cancer specimens and cell lines that were insensitive to radiation therapy, as compared with sensitive cancer specimens and the cell lines. We also found that miR-221 negatively regulated the expression of PTEN. The role of miR-221 in conferring cellular resistance to radiation treatment was validated in cell culture models. The effect of miR-221 on radio-resistance was mediated through targeting the 3’-UTR of PTEN gene. Conclusions: The expression level of miR-221 in gastric cancer may serve as a biomarker for sensitivity to radiation therapy, and targeting miR-221 may mean a new approach to sensitizing gastric cancer to radiation treatment. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 254P Elucidation of the mechanism of high-lymph node metastasis density in gastric cancer-H19-PEG10 axis S. Ishii, K. Yamashita, T. Tanaka, N. Nishizawa, K. Yokoi, H. Katoh, M. Watanabe Surgery, Kitasato University School of Medicine, Sagamihara, Japan Background: Lymph node ratio (LNR) is the ratio of metastatic lymph nodes to the lymph node dissection, in recent years it has become known as a strong prognostic factor and considered for inclusion of new staging system in gastric cancer. However, there has been no comprehensive study to identify molecules that showed the expression and the mechanisms associated with LNR in advanced gastric cancer. Therefore, we aim to reveal the molecular mechanism and select molecules that indicate the expression associated with a high LNR in advanced gastric cancer. Methods: In pathological Stage III (JCGC13) advanced gastric cancer tumor specimens, the candidate genes associated with high LNR were selected using a microarray for patients with high LNR (n ¼ 4) and those with low (n ¼ 4), and non-cancerous gastric mucosa as a control (n ¼ 2). The identified candidate genes have been verified as an association with high LNR in 39 Stage III advanced gastric cancer patients. Results: Rigorous analysis of the microarray result identified 5 candidate genes as H19, PEG10, IGF2BP3, CD177, and PGA3. Correlation between the five candidate genes and LNR has been verified by semi-quantitative RT-PCR in clinical specimens 39 cases. H19 and PEG10 showed a high expression frequency and significant difference (82.4%vs36.4%, 70.6%vs40.9%, p ¼ 0.004, p ¼ 0.034, respectively) in high LNR group compared with low. Intriguingly, there was significant association in expression between H19 gene and PEG10 gene (p ¼ 0.0002). Conclusions: In recent years, H19 has been reported to be involved in proliferation, invasion, and metastasis through epithelial-mesenchymal transition (EMT). On the other hand, PEG10 also has been elucidated for relationship with proliferation and invasion, metastasis. Primary cancer with high LNR showed high expression of both genes, so therapeutic effects of both gene knockdown are promising to identify molecular target signals in gastric cancer with high LNR, which is a clinical concern. Legal entity responsible for the study: Kitasato University School of Medicine, Surgery Funding: Merck Serono Co., Ltd. Disclosure: All authors have declared no conflicts of interest. 255P Predictive value of ERCC1, ERCC2, ERCC4, and glutathione S-transferase P1 for FOLFIRINOX in unresectable pancreatic cancer S. Tezuka1, M. Ueno2, S. Ohkawa2, A. Hirotani2, Y. Totsuka2, S. Moriya2, S. Kobayashi2, M. Morimoto2, Y. Nakamura3, Y. Miyagi2, S. Maeda4 1 Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan, 2Department of Hepatobiliary and Pancreatic Oncology, Kanagwa Cancer Center, Kanagawa, Japan, 3Department of Molecular Pathology and Genetics, Kanagawa Cancer Center Research Institute, Yokohama, Japan, 4Department of Gastroenterology, Yokohama City University Hospital, Yokohama, Japan Background: FOLFORINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) is one of the current standard chemotherapy, along with gemcitabine plus nab-paclitaxel, for unresectable pancreatic cancer. However, it has a high level of toxicity including neutropenia and febrile neutropenia and has limitation in its indication. Presently, there are no predictive biomarkers for FOLFIRINOX. A correlation between increased excision repair cross-complementing 1 (ERCC1) expression and nonresponse to FOLFOX has been reported for colon cancer. Therefore, in this study, we examined the expression of ERCC1, ERCC2, ERCC4, and Glutathione S-TransferaseP1 (GSTP1) as predictive biomarkers related to sensitivity to platinum agents. Methods: The study population consisted of 34 patients (median age, 61 years) with unresectable pancreatic cancer who were treated with FOLFIRINOX. The expressions of ERCC1, ERCC2, ERCC4, and GSTP1 were examined using immunohistochemistry. The clinical outcome was investigated in terms of overall survival (OS), progression-free survival (PFS), response rate (RR), disease control rate (DCR), and the frequency of grade 3 or 4 neutropenia. Whether some background factors, such as ECOG performance status (PS) and neutrophil-to-lymphocyte ratio (NLR) contributed to clinical outcome was evaluated by the Cox proportional hazards model. Results: ERCC1, ERCC2, ERCC4, and GSTP1 were positive in 64%, 24%, 18%, and 64% of cases. There were no significant differences between outcomes and the expression patterns. The frequency of grade 3 or 4 neutropenia also did not correlate with the expression patterns. Multivariate analysis revealed that ECOG PS of 1 significantly impacted OS (HR: 9.50, 95% CI: 2.25–40.07, P ¼ 0.002) and PFS (HR: 4.95, 95% CI: 1.75–14.00, P ¼ 0.003) compared with PS of 0, and the NLR ⭌5 affected OS (HR: 6.02, 95% CI: 1.20–30.29, P ¼ 0.03). Conclusions: ERCC1, ERCC2, ERCC4, and GSTP1 were unlikely to be predictive biomarkers of FOLFIRINOX in this setting. Legal entity responsible for the study: Shun Tezuka doi:10.1093/annonc/mdw582 | ix79 abstracts Funding: Kanagawa Cancer Center Disclosure: All authors have declared no conflicts of interest. 256P Recombination signal binding protein for immunoglobulinkappa-J region (RBPJ) and Mastermind-like 3 (MAML3) are potential therapeutic targets for pancreatic cancer A. Yamasaki1, H. Onishi1, M. Nakamura2 Cancer Therapy and Research, Kyushu University Hospital, Fukuoka, Japan, 2 Deapartment of Surgery and Oncology, Kyushu University Hospital, Fukuoka, Japan 1 Background: We have reported that Hypoxia induces Smo transcription, which is driver gene of Hh signaling, and that hypoxia enhances invasion and proliferation of pancreas cancer cells through increased Smo transcription. We have also reported protein-bound polysaccharide-K (PSK) can reduce Smo transcription under hypoxia. However, the precise mechanism of hypoxia-induced activation of Smo transcription remains unclear. Our goal is to find pivotal factors which regulates hypoxia-induced activation of SMO transcription and to detect a new effective therapeutic target for pancreatic cancer. Methods: Three pancreatic cancer cell lines (ASPC1, SUIT2 and PANC1) were cultured under normoxic and hypoxic (1% O2) conditions. DNA microarray analysis was performed using cells cultured under normoxia and hypoxia. RNA interference and plasmid were used to knock down and overexpress each genes. mRNA expression was estimated by Real time RT-PCR, and Protein expression was by Western blotting. Proliferation assay, Matrigel invasion assay were performed to investigate cell functions. We used PSK to block Smo transcription. Results: 1) A transcriptional regulator, recombination signal binding protein for immunoglobulin-kappa-J region (RBPJ) and a transcriptional co-activator, Mastermind-like 3 (MAML3) were picked up for candidate genes. 2) Expressions of SMO, RBPJ and MAML3 were increased under hypoxia in pancreatic cancer cell lines. PSK reduced these expressions under hypoxia. 3) RBPJ and MAML3 inhibition under hypoxia led to decreased SMO and GLI1 expressions. 4) Overexpression of RBPJ under hypoxia led to increased SMO expression and PSK reduced this increased expression. 5) Overexpression of RBPJ under hypoxia showed increased invasiveness and proliferation. PSK reduced these invasiveness and proliferation. Conclusions: These results suggest that hypoxia promotes SMO transcription through upregulation of MAML3 and RBPJ to induce proliferation, invasiveness in pancreatic cancer, and that MAML3 and RBPJ can be a new therapeutic target for pancreatic cancer. In addition to that, PSK can be a promising drug for pancreatic cancer by down regulating these new targets. Legal entity responsible for the study: N/A Funding: JSPS KAKENHI grant number 26293289 Disclosure: All authors have declared no conflicts of interest. 257P Molecular mechanisms involved in the synergistic interaction of novel formulated curcumin with gemcitabine in pancreatic cancer cells A. Avan1, S. Shahidsales2, F. Ghasemi3, S. Ahmadi-Simab4, R. Mahdavian Zadeh5, A. Sahebkar6 1 Department of Modern Sciences and Technologies, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran, 2 Radiotherapy Oncology, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran, 3Department of Modern Sciences and Technologies, Mashhad University of Medical Sciences, Mashhad, Iran, 4Cancer Research Center, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran, 5Department of Medical Biotechnology, Mashhad University of Medical Sciences, Mashhad, Iran, 6Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer related death. Despite extensive efforts, the poor prognosis of this disease has not improved over the past decades. Thus, there is an urgent need to develop novel anticancer agents that either exert a better efficacy than gemcitabine or improve gemcitabine activity in the context of combinatorial regimens. Against this background, the anticancer activity of curcumin has been investigated in different tumor types. Here we explored the molecular mechanism underlying the antitumor effect of four novel forms of curcumin (phytosomal) alone or in combination with gemcitabine in PDAC Methods: The viability of MIAPaCa-2, PANC-1 and PANC-2 cells was determined using MTT assay as well as in 3 dimensional cell culture model. We performed migration and invasion assays in the cells, while the perturbation of cell cycle was assessed by FACS before and after therapy ix80 | abstracts Annals of Oncology Results: Curcumin inhibited PDAC cell growth with IC50 of 100 nM in MiaPaCa-2, and synergistically enhanced the antiproliferative activity of gemcitabine and pro-apoptotic activity of gemcitabine. We then explored the cytotoxic activities of three formulated forms of curcumin (phospholipidated curcumin, amorphous curcumin and turmeric oleoresin) in the cells. The results revealed that the cell growth inhibition was more pronounced with amorphous curcumin. Moreover curcumin decreased cell migration/ invasion, which was associated with increased E-cadherin and reduced MMP9 expression. Curcumin mediated tumor shrinkage in spheroid model, enhanced the percentages of cells in S-phase, and significantly increased apoptosis. Moreover, curcumin suppressed Wnt pathway via modulation of survivin, and CyclinD1 Conclusions: Our data provide novel insights into the ability of curcumin to interfere with cell-proliferation, induce apoptosis, reduce migration/invasion and synergistically interact with gemcitabine in PDAC cells, supporting further studies on the therapeutic potential of this agent in treatment of pancreatic cancer Legal entity responsible for the study: N/A Funding: Mashhad University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. 258P First-line chemotherapies with FOLFIRINOX or gemcitabine plus nab-paclitaxel for unresectable pancreatic ductal adenocarcinoma in Japanese daily clinical practice M. Yano1, T. Terashima2, T. Yamashita2, M. Miyazawa3, H. Mizuno4, Y. Nomura5, H. Omura6, Y. Takata7, N. Ooishi2, H. Shugo8, K. Yamada9, H. Takabatake10, H. Takatori11, Y. Hodo12, R. Nishino13, T. Hayashi14, E. Mizukoshi2, S. Kaneko2 1 Internal Medicine(Gastroenterology), Toyama Prefectural Central Hospital, Toyama, Japan, 2Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan, 3Gastroenterology, National Hospital Organization Kanazawa Medical Center, Kanazawa, Japan, 4Gastroenterology, Toyama City Hospital, Toyama, Japan, 5Internal Medcine, FukuiKen Saiseikai Hospital, Fukui, Japan, 6 Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan, 7 Gastroenterology, Tonami General Hospital, Tonami, Japan, 8 Gastroenterology, Municipal Tsuruga Hospital, Tsuruga, Japan, 9 Gastroenterology, Keiju Medical Center, Nanao, Japan, 10Gastroenterology, Japanese Red Cross Kanazawa Hospital, Kanazawa, Japan, 11 Gastroenterology, Public Central Hospital of Matto-Ishikawa, Hakusan, Japan, 12 Gastroenterology, Saiseikai Kanazawa Hospital, Kanazawa, Japan, 13Internal Medicine, Hakui Public Hospital, Hakui, Japan, 14Gastroenterology and General Surgery, Yawata Medical Center, Komatsu, Japan Background: FOLFIRINOX (FFX) and gemcitabine (GEM) plus nab-paclitaxel (GnP) have been available for unresectable pancreatic ductal adenocarcinoma (PDAC) treatment since December 2013 and December 2014, respectively, in Japan. We conducted a multi-center retrospective study to investigate first-line chemotherapies in daily clinical practice for unresectable PDAC over the last 4 years. Methods: We retrospectively reviewed the medical records of 530 patients diagnosed with unresectable PDAC between August 2012 and July 2015. Results: The median patient age was 73 years, and 54% were men; the ECOG performance status (PS) was 0 in 50%, 1 in 33%, and 2 or greater in 17%. The patients with primary PDAC were classified as having UICC stage III (20%) or IV disease (69%), and 9% had a postoperative recurrence. A total of 392 patients (74%) were treated with anti-tumor therapies: chemotherapy (87%), chemoradiotherapy (10%), or other (3%); the remaining patients were treated with supportive care. As first-line chemotherapy, among 153 patients diagnosed in 2012 and 2013, 58% were treated with GEM and 20% were treated with S-1; among 114 patients diagnosed in 2014, 47% were treated with GEM, 23% with S-1, and 20% with FFX; and among 75 patients diagnosed in 2015, 31% were treated with FFX, 25% with GnP, and 23% with GEM. The objective response rate based on RECIST v1.1 was 14.8% after treatment with FFX, 36.8% with GnP, and 4.6% with GEM. The median survival was 9.8 months after FFX treatment, 9.5 months after GnP, 6.2 months after GEM, and 2.0 months after best supportive care. Grade 3 or greater neutropenia, anemia, and thrombocytopenia were observed in 64%, 11%, and 9% of the patients treated with FFX; 45%, 25%, and 10% with GnP; and 15%, 7%, and 8% with GEM, respectively. Second-line chemotherapy was conducted in 80% of the patients in the FFX group, 67% in the GnP group, and 43% in the GEM group. Conclusions: The use of FFX and GnP as first-line chemotherapy for patients with PDAC has recently increased. These two regimens are feasible and improved the antitumor effect and patient prognosis in daily clinical practice in Japan. Legal entity responsible for the study: Kanazawa University Funding: Kanazawa University Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology 259P Thromboembolism incidence in patients with pancreatic cancer receiving chemotherapy: A single-institutional retrospective cohort analysis C. Matsuda Gastroenterology, Sapporo City General Hospital, Sapporo, Japan Background: Although cancer and its treatments are well-recognized risk factors for thromboembolism (TE), such as venous and pulmonary TE, there are very few data of the incidence of cancer associated TE in the Asian population. So we conducted a retrospective cohort study to investigate the TE incidence of pancreatic cancer (PC) patients (pts) receiving chemotherapy in a Japanese community hospital’s daily practice setting. Methods: All the patients received chemotherapy for GTC in our hospital from January 2008 to May 2015 were identified through medical records review extracted by our hospital data warehouse. We analyzed the incidences of TE by reviewing all the reports of contrast-enhanced computed tomography performed on each patient during chemotherapy and identified the association between several clinicopathological factors and TE incidence using chi-square tests and logistic regression. Results: One hundred sixty eight Japanese PC pts were analyzed on this study. Patient characteristics were as follows; male/female 94/74, median age 70.8 (range 40 -92), nonadjuvant (non-Adj)/adjuvant (Adj) setting113/55, tumor-bearing (TB)/non-TB pts 3/ 165, multiple primary (MP)/single primary (SP) pts19/149. The incident rate with TE in PC pts was 15.48% (n ¼ 168), respectively. In relation to the status of malignancy, the incidence of TE was 12.4% (n ¼ 113) and 21.8% (n ¼ 55) in non-Adj and Adj setting, 5.26% (n ¼ 19) and 16.7% (n ¼ 149) in MP and SP pts, respectively. Conclusions: We found that there were significantly higher incidences of TE in nonAdj and SP compared with Adj and MP pts, respectively. Although the ethnic differences of the TE incidence rate between Caucasian and Asian population were reported, the incidence of Asian population received cancer chemotherapy remains unclear yet. So further accumulation of data are necessary to establish a Guideline for Asian to prevent and manage TE occurred during cancer chemotherapy such as ESMO or ASCO guidelines. Legal entity responsible for the study: Michio Nakamura, Taichi Murai, Kazufumi Itaya, Takayuki Sone, Masataka Yagisawa, Yuta Koike, Ayana Endo, Yoko Tsukuda, Yuji Ono, Takahiko Kudo, Atsushi Nagasaka, Shuji Nishikawa Funding: Sapporo City General Hospital Disclosure: All authors have declared no conflicts of interest. 260P Functional assessment of elderly cancer patients F. Nagashima, J. Furuse Department of Medical Oncology, Kyorin University School of Medicine, Mitaka, Japan Background: The mission of the Geriatric Study Committee (GSC) of the Japan Clinical Oncology Group (JCOG) is to establish the methodological schemes for clinical trials of elderly cancer patients. We previously reported that continuous geriatric assessments (GAs) repeated every two months are feasible in elderly patients with various types of cancer. We performed a prospective study of continuous geriatric assessments (GAs) in elderly advanced pancreatic cancer with gemcitabine-based chemotherapy. We evaluated the usefulness of the GAs to predict the prognosis. Methods: The key eligibility criteria for enrollment in the study were pathologically confirmed unresectable pancreatic cancer, age of 70 years or more, ECOG PS 0-2, and no prior chemotherapy or radiotherapy. Patients received gemcitabine (GEM) monotherapy or GEM-based chemotherapy. We examined the GAs before treatment and after two months of treatment. We performed the GAs using Cancer-Specific Geriatric Assessment (CSGA) in Japanese version, Mini Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Vulnerable Elderly Survey (VES)-13. Results: Fifty-two patients were enrolled in the study. The median age was 78 years (range 70-87 years). Forty-one patients were treated with GEM monotherapy and 9 with GEM and nab-paclitaxel. 90% of patients (44/49) received chemotherapy over two months. Conclusions: In elderly patients with pancreatic cancer who received GEM based chemotherapy, continuous GAs (MMSE, FAB, CSGA and VES-13) were feasible. This study is ongoing, we will report the relationship between changes of scores in the GAs and clinical outcomes. Clinical trial indentification: UMIN000010666 Legal entity responsible for the study: N/A Funding: Agency for Medical Research and Development of Japan Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 261P Efficacy of chemotherapy in patients with unresectable or metastatic pancreatic acinar cell carcinoma: Potentially improved efficacy with oxaliplatin-containing regimen J. Cheon, C. Yoo, B. Kim, K-P. Kim, J-L. Lee, T.W. Kim, B-Y. Ryoo, H-M. Chang Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Background: Pancreatic acinar cell carcinoma (ACC) is a rare cancer of the exocrine pancreas. Because of its rare incidence, efficacy of chemotherapy in this patient population has been largely unknown. Therefore, we retrospectively analyzed the outcomes of patients with advanced pancreatic ACC who received chemotherapy. Methods: Between January 1997 and March 2015, 15 patients with unresectable or metastatic pancreatic ACC who received systemic chemotherapy were identified in Asan Medical Center, Korea. Results: Median age was 58 years (range, 29–72 years). Eleven (73%) and 4 (27%) patients had recurrent/metastatic and locally advanced unresectable disease. Median overall survival in all patients was 20.9 months (95% CI, 15.7–26.1 months). As first-line therapy, intravenous 5-FU or oral fluoropyrimidine were administered in 6 patients (40%), gemcitabine in 5 (33%), gemcitabine plus capecitabine in 2 (13%), and FOLFOX in 2 (13%). Objective response rate (ORR) was 33% and median progression-free survival (PFS) was 5.8 months (95% CI, 3.1–8.4). After progression, second-line chemotherapy was administered in 8 patients; 4 patients received FOLFOX and the other 4 patients received gemcitabine. ORR was 38%, and patients administered FOLFOX had significantly better PFS than those administered gemcitabine (median 6.5 vs. 1.4 months, p ¼ 0.007). The ratio of Time to tumor progression (TTP) at first-line chemotherapy to TTP at second-line chemotherapy was significantly higher in patients administered FOLFOX (4.07 [range, 0.87–8.30]) than in those administered gemcitabine (0.12 [0.08–0.25]; p ¼ 0.029). Conclusions: Our results suggest that oxaliplatin-containing regimens may have improved activity against pancreatic ACC. Legal entity responsible for the study: Jaekyung Cheon, Asan Medical Center Funding: N/A Disclosure: All authors have declared no conflicts of interest. 262P MRI and MDCT for the diagnosis of pancreatoduodenal zone tumors O.R. Teshaev1, M.K. Khodjibekov2, G.E. Rakhmonova2 General Surgery for GP, Tashkent Medical Academy, Tashkent, Uzbekistan, 2 Oncology and Radiology, Tashkent Medical Academy, Tashkent, Uzbekistan 1 Background: Entering of the MRCP (magnetic resonance cholangiopancreatography) and MDCT (multidetector computed tomography) methods in medical oncology increased chance of diagnosing and monitoring of treatment of the tumors of pancreatoduodenal area as the other organ pathologic conditions and tumors. Almost all pancreatoduodenal area tumors give same symptoms and same clinical future, MRCP and MDCT can concretize results of traditional methods such as ultrasonography and cholangiography. And also gives chance to choose right treatment plan. Methods: MRCP with pathologic correlation was provided for 92 patients, 19-85 year sold, with complication of biliousness, nausea, poor appetite and itching sensation of skin in radiology department of Tashkent medical academy and department of radiology of the Research Center of Oncology of the Uzbekistan. Results: MRCP shows stable biliary hypertension with different etiologies: they are 43.5% head of pancreas, 30% tumor of portal area, 12% tumors of distal common bile duct, 8% tumors was from papilla of duodenum, 4.5% after metastasis, 2% due to liver tumors. Tumor size varied with its location and origin of tumor. Main sings by MRCP was dilated hepatic bile ducts untill 23 mm with irregular border and wall thickness. Mostly stable changes were founded in right side of biliary tree, with obvious deformation of biliary tree. In one case changing of biliary tree with visible clinical evidence such as biliousness was in young lady after trauma MRCP shoved stricture due to conjunctive tissue. In all patients local lymph nodes was enlarged until 0.8-1.2 cm. 5 patients tumors of pancreas origin was antral area tumors. Infiltration of stomach wall diameter was 14-23 mm. 4 patients tumor spreads till bifurcation of common hepatic bile duct, with large intrahepatic bile ducts with 16 mm, wall of these ducts was linear like (weak), walls between bile duct and portal vein was poor due to inflammation. Signal intensity was very low on these areas. Conclusions: MRCP gives chance to detect changing in biliary system, liver tissue and other adjacent structures. Shows growing rate of tumor, location, and structure of it. Clinical trial indentification: In the Section of Gastrointestinal noncolorectal cancer diagnostics. Legal entity responsible for the study: Rakhmonova Gulbahor Funding: Tashkent medical academy Disclosure: All authors have declared no conflicts of interest. doi:10.1093/annonc/mdw582 | ix81 abstracts 263P Annals of Oncology 265P Clinical sequencing system for pancreatic cancer as a laboratory examination H. Hayashi1, S. Tanishima2, R. Mori2, Y. Kawamoto3, I. Kinoshita4, Y. Komatsu3, H. Dosaka-Akita4, H. Nishihara1 1 Division of Clinical Cancer Genomics, Hokkaido University Hospital, Sapporo, Japan, 2Department of Biomedical Informatics Development, Mistubishi Space Software Co., Ltd, Tokyo, Japan, 3Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan, 4Department of Medical Oncology, Hokkaido University Hospital, Sapporo, Japan Background: We have launched in-house clinical sequencing system called “CLHURC” and started clinical sequencing for cancer patients as a medical service in clinical practice from April 2016. Since then we have conducted comprehensive genetic testing against several cancer-related genes for patients with all type of cancer including pancreatic cancer. Methods: In our system, genomic DNA was extracted from both pancreatic cancer tissue and normal blood serum obtained from the patients along with in-house clinical biobank system having high-quality tissue control and processing. Therefore we can utilize good quality genomic DNA for sequencing even if the tissue sample was obtained in tiny amount with endoscopic ultrasound-guided fine-needle aspiration biopsy. Gene alterations were identified using in-house automated gene analysis system. Attaching a meaning to the gene alterations and recommended treatment based on genomic information were discussed at the team-conference consisting of medical oncologists, pathologists, clinical laboratory technologists, bioinformaticians and clinical geneticists. We consequently make out a report for individual patient with genomic information including actionable gene alteration, druggable gene alteration, variant of uncertain significance, microsatellite instability and mutation rate. The period from the initial visit to the reporting the results to the patients was aimed at achieving within 14 days. Results: We had performed a clinical sequencing using CLHURC system for 43 cancer patients in four months (from April 1 to July 31 2016). Of them, the number of pancreas cancer patients was seven. Actionable gene mutation was detected in all of them (7/7, 100%), however potentially druggable gene mutation was detected only in two of them (2/7, 30%). Incidental germline gene mutation was detected in one of them (1/7, 14%). Conclusions: Gene profile based treatment strategy and subsequent attempt to realize precision medicine for pancreatic cancer are steadily ongoing in an effort to achieve improved treatment outcome of the disease. Legal entity responsible for the study: Hideyuki Hayashi Funding: Hokkaido University Hospital Disclosure: All authors have declared no conflicts of interest. S. Labidi, M. Nasri, H. El Benna, N. Mejri, M. Afrit, H. Rachdi, H. Boussen Medical Oncology, Abderrahmen Mami Hospital, Ariana, Tunisia Background: We aim to report epidemiological features, outcome, and prognosis of cholangiocarcinoma in a Tunisian population and try to identify its potential prognostic factors. Methods: Data of 51 patients treated from 2012 to 2015 were collected from the department dataset, including: patient’s characteristics, radiologic and biologic findings, treatment modalities and outcome. Kaplan Meier method and Cox proportional hazards analysis were used to relate clinical variables to overall survival (OS). Results: Median age was 58 years (range 40- 89 years), 53% were males. PS was 0-1 in 74%, and an average BMI of 24.6 kg/m2. Serum CA19-9 and CEA were increased in 43% and 23.5% of cases respectively. Primary tumor sites were gallbladder in 45% of cases, the hepatic hilum in 22%, intrahepatic in 20% and low bile duct in 14% of cases. Only 9 patients underwent curative surgery, followed by adjuvant gemcitabine-based chemotherapy in 5 cases. Neoadjuvant chemotherapy was indicated for 13 patients (Gemox regimen 8 cases, Gemcis 3 cases and gemcitabine 2 cases). Disease was diagnosed at metastatic stage in 53% of cases, mostly to liver (78%) and peritoneum (30%). First line chemotherapy regimens were gemcitabine based in most cases (17/ 19cases). The median OS was 12 months for patients treated with curative intent, and 9 months in the palliative setting. Median time to progression was 4 months, and 40.7% of the patients could have a 2nd line treatment. In the univariate analysis, age less than 50 years (p ¼ 0.038, HR ¼ 3.2 [95% CI, 2.05-5.01]), good PS(0-1) (p ¼ 0.000, HR ¼ 1.03[95% CI, 1.02-1.067]), adjuvant chemotherapy (p ¼ 0.029, HR ¼ 4.78 [95% CI, 1.14-19.94]) and surgical treatment with curative purpose (p ¼ 0.018, HR ¼ 2.87 [95% CI, 1.198-6.884]), were significantly associated with OS . In multivariate analysis, surgical treatment with curative purpose was defined as a solo independent prognostic factor for OS (p ¼ 0.03, HR ¼ 9 [95% CI, 2.05-16.88]). Conclusions: BTC remain diagnosed in Tunisia at locally advanced and/or metastatic stages impairing the prognosis. For the rare early cases, our results provide novel evidence that surgical treatment with curative purpose is an independent survival factor for BTC patients. Legal entity responsible for the study: Abderahman Mami Hospital Funding: Abderahman Mami Hospital Disclosure: All authors have declared no conflicts of interest. 266P 264P Combined chemoradiotherapy in patients with locally advanced pancreatic cancer A. Ivanova, I. Gladilina, E. Voronchikhina Radiosurgery, N. N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation Background: Pancreatic cancer (PC) – the most serious oncological disease with a unfavorable prognosis. Every year in the world recorded more than 230000 primary patients, 98% of them die. Over the past 5 years, the incidence of pancreatic cancer has increased by 4.2% in men and 12.1% in women. Radical operation in patients with PC is possible to perform only 25% of cases. Among operated patients 5-year overall survival was 20%, and for locally advanced PC (LAPC) 5-year overall survival rate was 8.7%. One of the areas will improve the treatment of LAPC was the use of chemotherapy triplets in combination with stereotactic body radiotherapy (SBRT). Methods: During the period 2014-2016 in NN Blokhin CRC 48 patients with LAPC were treated with 6 courses of FOLFIRINOX and SBRT (dose per fraction 7.5 Gy, total dose 37.5 Gy). Among these patients was 32 male and 16 female. Most commonly patients complain of pain in the epigastric area intractable narcotic analgesics. In this study was evaluated toxicity by chemotherapy, objective response rate and quality of life. Results: 80% of patients had a hematologic toxicity I grade, 2 patients had a III grade. For all patients was conducted computed tomography, ultrasound after SBRT. After treatment pain disappeared in 23 patients and 11 patients had a decrease in pain intensity. The most common side effect after irradiation was a diarrhea I grade. Objective response rate was 70% after treatment. Conclusions: Combined chemoradiotherapy including FOLFIRINOX and SBRT is an effective, well-tolerated in patients with LAPC. Legal entity responsible for the study: NN Blokhin Cancer Research Center Funding: NN Blokhin Cancer Research Center Disclosure: All authors have declared no conflicts of interest. ix82 | abstracts Epidemiology, outcome and prognostic factors of biliary tract cancer in the Tunisian population Elevation of neutrophil-to-lymphocyte ratio before first-line chemotherapy predicts a poor prognosis of second line chemotherapy in gastric cancer D. Inoue1, A. Nakazono1, F. Hatao2, K. Imamura2, S. Namiki1 Depaetment of Gastroenterology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan, 2Department of Surgery, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan 1 Background: Previous studies have shown a high-level of evidence which supports the use of second-line chemotherapy in patients with gastric cancer, but not enough prognostic factors have been established. Recent studies suggested that the neutrophilto-lymphocyte ratio (NLR) was closely associated with cancer patient prognosis. The aim of our study is to examine the prognostic value of NLR in patients with gastric cancer, especially focusing on the relationship between NLR and the efficacy of secondline chemotherapy. Methods: This is a retrospective study, and the clinicopathological findings before the initiation of chemotherapy were analyzed. Selection criteria was as follows; patients who 1) received paclitaxel or irinotecan as a second-line chemotherapy in our hospital between January 2010 and June 2015, 2) had histologically confirmed unresectable gastric adenocarcinoma, 3) followed- up until death or for 180 days or longer. The primary endpoint was overall survival of second-line chemotherapy. NLR level of 3.0 was selected as cut-off value for validation. Kaplan-Meier survival plots were generated based on NLR level and the curves compared by using the log-rank test. The relationship between each baseline variable and long-term survival was investigated by univariate and multivariate Cox regression analyses. Results: There were 86 patients who met the selection criteria. In second line chemotherapy, the median OS was 9.9 months (95% CI, 6.0-13.8) in normal NLR patients as compared with 5.5 months (95% CI, 5.0-5.9) in elevated NLR patients (P ¼ 0.002). On the other hand, there were no statistically significant difference in first line, the median OS was 18.9 months (95% CI, 15.1-22.8) in normal NLR patients as compared with 14.6 months (95% CI, 11.2-18.0) in elevated NLR patients (P ¼ 0.157). The univariate and multivariate Cox regression analysis revealed that NLR was an independent predictive marker for second-line chemotherapy. Conclusions: The second-line chemotherapy may not be benefit if elevation of NLR was seen before the initiation of the first-line chemotherapy in patients with advanced gastric cancer. Legal entity responsible for the study: Tokyo Metropolitan Tama Medical Center Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology Funding: Tokyo Metropolitan Tama Medical Center Disclosure: All authors have declared no conflicts of interest. 267P Irinotecan monotherapy as third line treatment for advanced gastric cancer patients refractory fluoropyrimidine, platinum and taxanes harboring UGT1A1*1/*1. *1/*6 or *1/*28 N. Sugimoto, T. Yoshinami, T. Yagi, A. Hasegawa, F. Fujisawa, F. Imamura Clinical Onocology, Osaka Medical Center for Cancer and Cardiovascular Dideases, Osaka, Japan Background: Several randomized trials demonstrated the survival benefit in advanced gastric cancer (AGC) patients receiving second-line chemotherapy. RAINBOW study showed that ramucirumab with paclitaxel combination chemotherapy significantly increased overall survival time compared with paclitaxel alone, and be regarded as the standard second-line treatment for AGC. As a result, irinotecan monotherapy is considered to be a third-line treatment for AGC, but the efficacy and safety is still unclear, especially harboring UGT1A1 . Methods: The selection criteria were pathologically proven AGC; 20 years or older; refractory to fluoropyrimidine with platinum as first-line chemotherapy; refractory to taxanes as second-line chemotherapy; no prior irinotecan; performance status 0,1 or 2; able to oral intake; UGT genetic polymorphisms of UGT1A1*1/*1. *1/*6 or *1/*28; and adequate organ functions. Patients were administered irinotecan 150mg/m2 as thirdline every two weeks. until disease progression, unacceptable toxicity, or pts’ refusal between December 2010 and May 2016. Results: The analysis covered 20 patients over the period from December 2010 to May 2016. The median age was 68 years (range, 46-80); 16 males and 4 females; ECOG PS 0-1/2, 19/1; peritoneal dissemination þ/-, 14/6; number of metastatic sites 1-2/3or more, 15/5. Median progression-free survival was 74 days (95%CI 56-133) and median overall survival was 278 days (95%CI 131-431) from the initiation of irinotecan administration. Response rate and disease control rate was 10% and 45%, respectively. Median relative dose intensity was 86.2% (66.1 mg/m2/week); 4 pts needed dose reduction in the second course. The rate of grade 3 or 4 toxicity were leucopenia (15%), neutropenia (20%), anemia (15%), and febrile neutropenia (5%). Neither grade3 diarrhea nor treatment-related death was observed. Conclusions: This study suggests that irinotecan monotherapy as third-line has acceptable anti-tumor effect and manageable toxicity in AGC pts harboring UGT1A1. Legal entity responsible for the study: Naotoshi Sugimoto Funding: N/A Disclosure: All authors have declared no conflicts of interest. 268P Sarcopenia may be associated with the mortality in patients with hepatocellular carcinoma S.E. Kim, J.W. Park, C.K. Park Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea Background: Sarcopenia has known as an independent predictor of clinical outcomes in patients with hepatocellular carcinoma (HCC). In this study, we aimed to investigate the association of sarcopenia with the mortality in patients with HCC. Methods: A total of 193 HCC patients were subjected. All enrolled patients had a computed tomography at the level of the third lumbar (L3) vertebrae to determine the L3 skeletal muscle index. Sarcopenia was defined using previously established cutpoints. They were followed up for a median 12 months (range, 1-80). Results: Median age was 58 years (range, 36-86), 80% of patients were male, 62% Child –Pugh class A and 70% were positive for HBsAg. Only 23 patients (12%) could undergo curative treatment (surgical resection, liver transplantation, radiofrequency ablation) Sacopenia was present in 106 patients (55%). By univariate analysis, sarcopenia (OR ¼ 2.08; 95% CI 1.12-3.87: P ¼ 0.021), Child-Pugh score (OR ¼ 1.38; 95% CI 0.92191.12: P < 0.001), tumor number (OR ¼ 3.01; 95% CI 1.55-5.85: P ¼ 0.001), tumor size (OR ¼ 1.10; 95% CI 1.02-1.187: P ¼ 0.01), portal vein thrombosis (OR ¼ 3.00; 95% CI 1.45-6.21: P ¼ 0.003) and curative treatment of HCC (OR ¼ 0.13; 95% CI 0.04-0.39: P < 0.001) were associated with mortality. By multivariate analysis, sarcopenia (OR ¼ 2.13; 95% CI 1.01-4.54: P ¼ 0.021) and curative treatment of HCC (OR ¼ 0.26; 95% CI 0.08-0.87: P ¼ 0.029) were closely associated with mortality. There was no correlation with age, gender, cirrhosis, diabetes mellitus, prevalence of hepatitis surface antigen positivity, underlying renal function, body mass index, platelet count, baseline AFP level, Child-Pugh score, tumor size, tumor number and portal vein thrombosis. Conclusions: Our data suggested that sarcopenia and curative treatment of HCC may be closely associated with the mortality in HCC patients. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 269P Transarterial ethanol ablation combined with transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus B. Yang, Z. Liao Abdominal Oncology, West China Hospital, Huaxi, Sichuan University, Chengdu, China Background: Portal vein tumor thrombus (PVTT) can be detected in 30-62% of patients with Hepatocellular Carcinoma (HCC). HCC with PVTT is considered to have an extremely poor prognosis. The reported median survival for untreated HCC patients with PVTT is 2.7 months, whereas survival in patients without PVTT is 24.4 months. There are no effective treatment options for PVTT, especially end-stage PVTT (Vp3/ Vp4). Therefore, there is a critical need for an effective treatment strategy for PVTT(Vp3/Vp4). This prospective study aimed to evaluate the technical feasibility, effectiveness and safety of transcatheter chemoembolization (TACE) for tumors in the liver parenchyma plus transarterial ethanol ablation (TEA) for PVTT(Vp3/Vp4). Methods: A cohort study was carried out with 21 patients in the TACEþTEA group under the supervision of cone beam computed tomography and 22 patients in the TACE group. Treatment included transcatheter delivery of a lipiodol–ethanol mixture (LEM, 1:1 ratio by volume) for TEA and epirubicin–lipiodol emulsion (50 mg) for TACE. Results: Mean survival was 7.2 months in the TACEþTEA group (1.81 6 0.93 courses) and 3.9 months in the TACE group (1.86 6 1.08 courses) (p ¼ 0.006). Patients treated with TACEþTEA had better overall survival (at 3-months, 6-months and 12-months, respectively) compared to patients treated with TACE alone (90.2% vs 86.4%, 79.6% vs 59.1% and 53.1% vs 18.8%; p ¼ 0.006). The rate of PVTT regression was higher in the TACEþTED group (89.5%) than in the TACE group (20%) (P < 0.001). TACEþTEA also complained with more complications than TACE, which may can be came from destruction the PFA of ethanol. Fifty-one complications occurred in the TACEþTEA group, while 47 complications occurred in the TACE group (P ¼ 0.481). Conclusions: We found that occluding the arterial supply to PVTT with the help of TEA not only resulted in recanalization of the portal vein, but also significantly improved survival. Based on the results of this study, TACE combined with TEA was more effective than TACE alone for treating HCC with PVTT. TEA for treating PVTT is safe, feasible and prolongs overall survival. Legal entity responsible for the study: This study was sponsored by National Nature Science Foundation of China (81470141) Funding: This study was sponsored by National Nature Science Foundation of China (81470141) Disclosure: All authors have declared no conflicts of interest. 270P Benzyl-isothiocyanate induces apoptosis and inhibits migration and invasion of hepatocellular carcinoma cells in vitro M. Li, M. Zhu, W. Li, J. Guo Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Hainan, China Background: Despite consideration of benzyl isothiocyanate(BITC) is applied to prevention and therapeutic of cancer, the role of BITC in inducing apoptosis and inhibiting migration and invasion of hepatocellular carcinoma (HCC) cell is still unclear. In this study, we aims to explore the effects of BITC on the growth and migration and invasion of HCC cells in vitro.Despite consideration of benzyl isothiocyanate(BITC) is applied to prevention and therapeutic of cancer, the role of BITC in inducing apoptosis and inhibiting migration and invasion of hepatocellular carcinoma (HCC) cell is still unclear. In this study, we aims to explore the effects of BITC on the growth and migration and invasion of HCC cells in vitro. Methods: Human HCC cell lines, Bel 7402 and HLE, were treated with an optimal concentration of BITC for 48 hours, and the growth and apoptosis of HCC cells were detected using the MTT method, fluorescent microscopy and flow cytometry. The migratory and invasive abilities of HCC cells were detected by Transwell assay, the MMP2 and MMP9 enzymatic activities were assayed by gelatin zymography, and the expression of apoptosis-related proteins and metastasis-related proteins was detected by Western blotting. Results: MTT, fluorescent microscopy and flow cytometry analyses indicated that BITC inhibits growth and promotes apoptosis of HCC cells; BITC has a significant inhibitory effect on the migration and invasion of HCC cells. BITC stimulated expression of caspase-3/8 and PARP-1 and suppressed expression of survivin, MMP2/9 and CXCR4. BITC also inhibited the enzymatic activities of MMP2 and MMP9. Conclusions: BITC was able to induce apoptosis and suppress the invasive and migratory abilities of Bel 7402 and HLE cells. The mechanism by which BITC is involved in these processes may include up-regulating the expression of apoptosisrelated proteins and down-regulating the expression of metastasis-related proteins. BITC may be a novel chemotherapy for HCC patients. Legal entity responsible for the study: Mengsen Li doi:10.1093/annonc/mdw582 | ix83 abstracts Funding: the National Natural Science Foundation of China Disclosure: All authors have declared no conflicts of interest. 271P Target therapy treatment patterns on advanced gastrointestinal stromal tumor (GIST) patients: a nation-wide cohort study in Taiwan I-J. Chiang1, C-Y. Yang2, Y-Y. Chen3, W-T. Fang4 Graduate Institute of Data Science, Taipei Medical Unversity, Taipei, Taiwan, 2 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, 3 Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung, Kaohsiung, Taiwan, 4Taiwan Division, Pfizer Limited, Taipei, Taiwan 1 Background: Imatinib and sunitinib are two reimbursed targeted therapies for advanced GIST in Taiwan. A national-wide study was performed to evaluate the targeted therapies in GIST treatment among Taiwanese population. Methods: We conducted a nationwide retrospective cohort study based on data from the National Health Insurance Research Database (NHIRD) between January 2005 and December 2010. All 1186 patients enrolled had histology-confirmed GIST with first-line imatinib (400mg qd) and follow-up more than one year. We estimated recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) probabilities with the Kaplan-Meier method. The proportional hazards assumption was verified by tests of correlations with time and examination of residual plots, and only variables that were deemed statistically significant were included in the final Cox model. Results: With a median follow-up for surviving patients of 42 months, the median PFS of the cohort was 31 months since first-line imatinib. Cox proportional hazards multivariate analysis demonstrated directly switching to sunitnib was significant (hazard ratio: 0.77; 95% CI: 0.55-1.08; p < 0.001) prognostic factor for post-imatinib OS (59 months vs. 47 months). The whole cohort was divided into three groups. Group A (n ¼ 585) had complete surgical resection and began imatinib treatment once recurrence confirmed. Group B (n ¼ 419) received imatinib therapy within 3 months after operation. Group C (n ¼ 182) was patients who were considered as unsuitable for operation. The median RFS of Group A was 16 months (95% CI 15-18) and the median OS after complete resection was 84 months. The cohort also demonstrated that PFS and OS of switching to sunitinib were longer than that with imatinib dose escalation after switching. Conclusions: Taiwanese advanced GIST patients who failed first-line treatment still gained benefit from either imatinib dose escalation or a switch to sunitinib. Significant improvement in PFS using sunitnib directly as switch maintenance in advanced GIST. Clinical trial indentification: In 1995, Taiwan launched a single-payer National Health Insurance program, and as of 2007, 22.60 million of Taiwan’s 22.96 million population were enrolled in this program. Each year, the Bureau of National Health Insurance, Taiwan, collects data, including registration files and original claim data for reimbursement, from the National Health Insurance, and sorts it into data files. These data files are de-identified by scrambling the identification codes of patients, medical institutions and physicians and sent to the National Health Research Institutes, Taiwan, to form the original files of the NHIRD. Therefore, these files contain all the records of individuals enrolled in the National Health Insurance program, and they are available for research purposes only. Legal entity responsible for the study: Taipei Medical University Funding: Pfizer Limited, Taiwan Division Disclosure: All authors have declared no conflicts of interest. 272P Annals of Oncology loss [weighted mean difference (WMD)¼-16.25 ml, 95% confidence interval (CI: 29.25,-3.25, p ¼ 0.270)], smaller incision length (WMD¼ -2.74, 95% CI:-4.60, 0.89;p<0.01). Bowl recovery was similar between 2 groups and overall length of hospital stay was equal (WMD¼-0.28,95% CI:-0.76, 0.20, p ¼ 0.761). The complication profile was similar with equality in anastomosis leakage (WMD¼0.83;95% CI:0.36,1.90;p¼0.686) and stricture (WMD¼0.98;95%CI:0.44,2.18;p¼ 0.847) as well as bleeding (WMD¼1.55;95%CI:0.45,5.35;p¼0.745). No inferiority in the number of retrieved lymph node (WMD¼1.41;95% CI:-0.45,3.28; p ¼ 0.296) as well as proximal margin (WMD¼0.11,95%CI: -0.11,0.33; p ¼ 0.346) was noticed. Conclusions: TLTG is shown by this meta-analysis to be efficient and safe in the short term outcome. Future studies should evaluate oncological outcomes with adequate long-term follow-up, preferably in randomized trials. Legal entity responsible for the study: National Cancer Center-Korea Funding: National Cancer Center-Korea Disclosure: All authors have declared no conflicts of interest. 273P K. Shingo, K. Kuribayashi, E. Fujimoto, Y. Koda, Y. Negi, E. Shibata, T. Otsuki, K. Mikami, T. Nakano Respiratory Medicine, Hyogo College of Medicine, Nishinomiya, Japan Background: Malignant peritoneal mesothelioma (PM) is a relatively rare disease accounting for 10% of all mesotheliomas that occur in the mesothelial cells of the pleura, peritoneum, pericardium, and tunica vaginalis testis, and its prognosis is poor. A standard therapy for malignant PM has not been established. Conventional therapies are employed for malignant PM in clinical settings; however, the treatment outcomes are unknown. This was a retrospective study to evaluate the effects of primary chemotherapy of CDDP þ PEM on patients with PM. Methods: Twenty-one subjects who were pathologically and definitively diagnosed with PM and received 2 or more cycles of first-line combination chemotherapy of CDDP þ PEM were included in this study. Treatment outcome was assessed using CT images based on RECIST. FDG-PET images obtained before and after the treatment were used for cases that were difficult to assess based on CT findings. Results: The median age of the patients was 60.6 years (32–76 years), and 13 men and 8 women were included. Histological types included 20 epithelial and 1 biphasic types while clinical conditions included 5 cases of ascites retention, 6 mass forming, and 10 mixed types. In assessment of tumor reduction effects, 2, 9, and 5 subjects achieved a CR (10%), PR (42%), and a SD (24%), respectively, and PFS and MST were 10.1 and 16.7 months, respectively. Epithelial and ascites retention predicted favorable outcome of chemotherapy. Conclusions: While PM is generally considered an extremely treatment-resistant malignant tumor, classical first-line therapy of CDDP þ PEM allowed us to demonstrate a response rate of 52% and PFS of 10 months or longer. Although this was a retrospective study, these results are more favorable than those observed for patients with primary mesothelioma in the pleura. Therefore, first-line systemic chemotherapy of CDDP þ PEM can be considered effective for patients with PM. Legal entity responsible for the study: Hyogo College of Medicine Funding: Hyogo College of Medicine Disclosure: All authors have declared no conflicts of interest. Meta-analysis of intracorporeal or extracorporeal anastomosis after laparoscopic total gastrectomy for gastric cancer: Which is better? A.T.T. Nguyen GCSP, National Cancer Center, Gyeonggi-do, Republic of Korea Background: Totally laparoscopic total gastrectomy (TLTG) is still uncommon because of the difficult of esophago-jejunostomy technique laparoscopically which almost depends on surgeon. So far, the benefit as well as the reality of TLTG is under controversial. The aim of this study was to determine the useful extent of this procedure. Methods: The literature on comparative studies of TLTG versus LATG up to now were extensively retrieved from database PubMed, Cochrane library, EMBASE. The operation times, blood loss, time to flatus, time to first oral intake, postoperative hospital stay, postoperative complications especially anastomosis leakage and anastomosis stenosis were analyzed. The statistical analysis was performed with STATs 13.0 software. Results: Nine studies met the inclusion criteria for meta-analysis. Odds ratios (ORs) and weighted mean differences (WMDs) were calculated with 95% confidence intervals (CIs) to evaluate the effect of TLTG. Compare to LATG, TLTG experienced less blood ix84 | abstracts Cisplatin in combination with pemetrexed in the treatment of patients for advanced malignant peritoneal mesothelioma: Retrospective study of 21 cases 274TiP A randomized phase 2 study of nanoliposomal irinotecan (nal-IRI, BAX2398)-containing regimen in Japanese patients with metastatic pancreatic adenocarcinoma (mPAC) T. Ioka1, M. Ueno2, H. Ueno3, S. Kabir4, T. Tokudome5, M. Ikeda6 Hepatobiliary and Pancreatic Oncology, Pancreatic Cancer Center, Osaka General Medical Center, Osaka, Japan, 2Department of Hepatobiliary and Pancreatic Oncology, Kanagwa Cancer Center, Kanagawa, Japan, 3 Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan, 4Clinical R&D, Oncology, Shire, Cambridge, MA, USA, 5 Clinical R&D, Oncology, Shire Tokyo, Tokyo, Japan, 6Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Chiba, Japan 1 Background: The global, phase 3 study (NAPOLI-1) demonstrated that nal-IRI, a liposomal formulation of irinotecan (BAX2398, MM-398), in combination with 5-FU/ LV significantly improved overall survival (OS) in patients with mPAC previously treated with gemcitabine-based therapy compared with 5-FU/LV (6.1 vs 4.2 months; unstratified hazard ratio 0.67; [95% CI 0.49–0.92; P ¼ .012]). The most frequent grade 3 adverse events in the nal-IRIþ5-FU/LV–treated patients were neutropenia Volume 27 | Supplement 9 | December 2016 Annals of Oncology (27%), diarrhea (13%), vomiting (11%), and fatigue (14%) (Wang-Gillam A. Lancet. 2016). Trial design: The ongoing open-label, phase 2 study (ClinicalTrials.gov, NCT02697058) is designed to evaluate the safety, PK, and efficacy of nal-IRIþ5-FU/ calcium levofolinate in Japanese patients with mPAC that progressed or recurred after prior gemcitabine-based therapy. This 2 part study involves a safety run-in (part 1) and a randomized, open-label study (part 2). Key eligibility criteria include: age 20 years; pathologically confirmed pancreatic cancer; metastatic disease with at least 1 measurable lesion as defined by RECIST v1.1 guidelines; documented disease progression after prior gemcitabine-containing therapy; KPS 70; no known metastases to the central nervous system; and adequate hematologic, hepatic, and renal functions. The primary objectives of part 1 are to assess the safety and tolerability of nalIRIþ5-FU/calcium levofolinate and to characterize the PK of nal-IRI in at least 6 patients. In part 2, an additional 74 patients will be randomly assigned 1:1 to nal-IRIþ5FU/calcium levofolinate alone (arm A) or 5-FU/calcium levofolinate (arm B) with progression-free survival as the primary objective. Secondary objectives of part 2 include characterization of PK and safety, and between-arm comparison of objective Volume 27 | Supplement 9 | December 2016 abstracts response rate, OS, time to treatment failure, disease control rate, CA19-9 response, and patient-reported outcomes using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire core module (EORTC-QLQ-C30) and patient diary. This study is currently recruiting patients at 16 sites in Japan. Legal entity responsible for the study: Shire Japan KK Funding: Shire Japan KK Disclosure: T. Ioka: Taiho, Astrazeneca, Yakult Honsha, Baxata and JCRO Speaker’s bureau; Taiho, Yakult Honsha, Daiichi Sankyo, Eisai, Mochida and Fuji Film Research fundings; Merk Serono, Taiho, Astrazeneca, Glaxo Smithkline, Nihon Zouki and Zeria. M. Ueno: Honoraria: Abbott; AstraZeneca; Boston Scientific; Kyowa Hakko Kirin; Lilly; Novartis; Taiho Pharmaceutical; Yakult Honsha; Research: AstraZeneca; Daiichi Sankyo; Eisai; Merck Serono; Taiho Pharmaceutical; Zeria Pharmaceutical. H. Ueno: Honoraria: Taiho Pharmaceutical Co., Ltd. Research Funding: Taiho Pharmaceutical Co., Ltd; NanoCarrier Co., Ltd.; Baxalta Japan Limited. S. Kabir, T. Tokudome: Shire employee. M. Ikeda: Honoraria: Taiho, Research funding: Taiho. doi:10.1093/annonc/mdw582 | ix85 Annals of Oncology 27 (Supplement 9): ix86–ix89, 2016 doi:10.1093/annonc/mdw583 Genitourinary tumours, non-prostate 275P Clinical outcomes of second transurethral resection in nonmuscle invasive high grade bladder cancer: a retrospective, multi-institutional, collaborative study N. Kamiya1, H. Suzuki1, T. Suyama2, M. Kobayashi3, S. Fukasawa3, N. Sekita4, K. Mikami4, N. Nihei5, Y. Naya2, T. Ichikawa5 1 Urology, Toho University Sakura Medical Center, Sakura, Japan, 2Urology, Teikyo University Chiba Medical Center, Sakura, Japan, 3Urology, Chiba Cancer Center, Chiba, Japan, 4Urology, Chibaken Saiseikai Narashino Hospital, Narashino, Japan, 5Urology, Chiba University, School of Medicine, Chiba, Japan (OS: 22.0 vs. 13.9 months for GC and MVAC, respectively, P ¼ 0.073), while there were no significant difference in survival between these two regimen for non-intense TIL (OS: 13.8 vs. 13.7 months for GC and MVAC, respectively, P ¼ 0.742). Conclusions: Our study confirmed the prognostic roles of stromal TIL for patients with mUC treated with cisplatin based chemotherapy. An external cohort was needed to validate our conclusion. Legal entity responsible for the study: N/A Funding: by myself Disclosure: All authors have declared no conflicts of interest. 277P Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: A systematic review and meta-analysis abstracts B. Malik Medical Oncology, Dow University of Health Sciences, Karachi, Pakistan Background: To evaluate the impact of second transurethral resection (TUR) on the clinical outcome of non-muscle invasive high-grade bladder cancer and to identify predictors of pT1 or deeper and residual tumor at the second TUR, a retrospective, multi-institutional collaborative study was conducted. Methods: 198 patients with non-muscle invasive high-grade bladder cancer in 5 medical institutions were enrolled from 2006 to 2013. All patients underwent second TUR within 1.5 months (mean) after the first resection. Clinicopathological findings of the first and second TURs were compared. Cancer-specific survival and recurrence-free survival were evaluated. Furthermore, univariate and multivariate analyses for predictors of residual cancer at the second TUR were performed using a logistic regression model. Results: At the second TUR, no tumor was found in 111 (56%) patients; 87 (44%) had residual cancer. Five pT1 patients at the first TUR (3%) were upstaged to pT2. One pTa patient at the first TUR (1%) was upstaged to pT1. Twelve G2 patients at the first TUR (6%) had tumor upgraded to G3. Patients in the less than pT1 group at second TUR had significantly better survival than those in the pT1 or deeper group. The number of tumors at the first resection was an independent risk factor for pT1 or deeper tumor at the second TUR. Conclusions: Second TUR is a valuable procedure for accurate staging of non-muscle invasive high-grade bladder cancer. The number of tumors at the first TUR was a significant independent predictor of pT1 or deeper tumor at the second TUR. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 276P The survival impact of stromal tumor-infiltrating lymphocytes for patients with metastatic urothelial carcinoma treated with cisplatin-based chemotherapy M-C. Hsieh, H-S. Huang, Y-L. Su, P-H. Chiang, C-H. Huang Hematology and Oncology, Chang Gung Memorial Hospital-Kaohsiung, Kaohsiung, Taiwan Background: Urothelial cancers usually recur distantly rather than loco-regionally. In patients with pT2 and pT3/pT4 tumors, local recurrence has been observed in 3–4% and 11–16%, respectively, whereas distant failure has occurred in 10–27% and 19–35%, respectively. Despite local therapy most patients with muscle invasive transitional cell carcinoma (TCC) of the bladder die of systemic relapse, indicating a need for effective adjunctive systemic treatment. We determined whether neoadjuvant chemotherapy improved overall survival. This study evaluated the role of neoadjuvant combination chemotherapy with gemcitabine/cisplatin (GC) in improving the outcome of this group of patients. Methods: A total of 44 patients (84% Male, 16% Female) with newly diagnosed bladder cancer (T3-4, N0-2, M0) were subjected to an initial 3 cycles of GC, then managed according to response. Patients were assessed clinically after each cycle and by Interim CT scan after 3 cycles of chemotherapy and those who achieved complete or partial response underwent radical cystectomy. Results: We enrolled 63 patients, 19 of whom were found to be ineligible; thus, 44 were assigned to receive neoadjuvant chemotherapy followed by surgery. Average size of the largest tumor was greater that 30mm in 77% patients. According to Computed Tomographic findings 70% patients belonged to stage T4A. The overall response rate to GC was 50%, and incomplete response was achieved in 25%, whereas 25% patients were lost to follow up. Twenty two patients who had a complete response, underwent cystectomy and diversion. It was observed that those patients who underwent radical cystectomy with ureterosigmoidostomy had increased serum creatinine in comparison to patients who had ileal conduit. Conclusions: The size of the effect is modest and combination chemotherapy can be administered safely without adverse outcomes resulting in delayed local therapy. Further efforts to identify the patients most likely to benefit from neoadjuvant therapy are necessary to optimize its use. Legal entity responsible for the study: Babar Malik Funding: SIUT Disclosure: All authors have declared no conflicts of interest. 278P Background: The prognostic role of stromal tumor-infiltrating lymphocytes (TIL) has been established among various cancers. This study aims to determine the survival impact of TIL in metastatic urothelial carcinoma (mUC) treated with cisplatin-based chemotherapy. Methods: A total of 164 mUC patients were included in the present analysis, consisting of 109 upper tract urothelial carcinoma and 55 urothelial carcinoma of bladder. The slides of primary tumors were collected to evaluate the percentage of TIL. TIL of each specimen was defined as intense and non-intense. The primary end point was overall survival (OS). Multivariate analysis was conducted to assess the prognostic factors. Chemotherapy response of gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin plus cisplatin (MVAC) were also compared between dense and non-dense TIL. Results: The median follow-up duration was 13.75 months. There were 99 intense TIL and 65 non-intense TIL. Patients harboring non-intense TIL trended to have more than one metastatic sites as compared with those with intense TIL (P ¼ 0.059). The median OS was 16.7 and 13.7 months for intense and non-intense TIL, respectively (P ¼ 0 .007). In multivariate analysis, intense TIL was an independent prognostic factor to better OS after correcting with confounding factors (hazard ratio: 0.76, 95% confidence interval: 0.62-0.90, P ¼ 0.002) . There were marginal survival benefits toward GC for intense TIL Sequential chemotherapy with gemcitabine plus carboplatin, followed by additional docetaxel for advanced upper-tract urothelial cancer patient with impaired renal function T. Yoneyama, T. Tanaka, T. Narita, M. Oikawa, K. Hagiwara, T. Yoneyama, A. Imai, S. Hatakeyama, Y. Hashimoto, T. Koie, C. Ohyama Urology, Hirosaki University, Hirosaki, Japan Background: GC therapy may be a promising regimen for advanced upper-tract urothelial cancer as well as for advanced bladder cancer. However, cisplatin is proved to be too toxic for the patients with impaired renal function. We retrospectively evaluated the effectiveness and adverse events (AEs) of a sequential chemotherapy with gemcitabineþcarboplatin(GCarbo) followed by GCcarboþ docetaxel (GCarboD) for advanced upper-tract UC whose eGFR was 60 ml/min/1.73m2 or below. Methods: We treated seventy-four patients with advanced upper-tract urothelial cancer (UTUC) at our clinic between August 2004 and December 2015. 55 patients (37 men and 19 women) whose eGFR were 60 ml/min/1.73m2 or below were enrolled. The average age was 71.0 (50–89), and average eGFR was 43.4 (11.6–59.7) ml/minute/ 1.73m2. Mean observation period was 27.7 (3–100) months. The patients received 2 C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts Annals of Oncology courses of GCarbo consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCcarbo was performed. If this regimen did not induce any tumor size reduction, we switched to 2 courses of GCarboD (D; 70mg/m2) treatment as second-line treatment. Results: GCarbo regimen yielded 4 cases (7.3%) of CR, 25 (45.5%) of PR, and the average duration of response of 16.1 (2–98) months. GCarboD treatment was administered in 14 cases, and yielded 2 (14.3%) PR and a duration of response was 39.5(7-72) months. The median survival period was 14.3 months. As for AEs with GCcarbo regimen, there were 18 (45.0%) of G3/4 blood toxicity, whereas only 5 (12.5%) developed digestive symptoms. In GCarboD regimen, there were 14 (92.9%) of blood toxicity and 5 (35.7%) of gastrointestinal AEs. Conclusions: Although the present study is small and preliminary, the present sequential chemotherapy is safe and active for advanced UTUC with impaired renal function. GCarbo regimen achieved acceptable response rate (52.8%). The median overall survival of 14.3 months is acceptable when eGFR of 43.7 ml/min/1.73m2 for the subjects is took into consideration. However, GCarboD had limited effectiveness for non-responder of GCarbo. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 279P Quality of life during gemcitabine plus cisplatin or gemcitabine plus carboplatin for urothelial carcinoma S. Hatakeyama, T. Yoneyama, Y. Hashimoto, T. Koie, C. Ohyama Urology, Hirosaki University, Hirosaki, Japan Background: To compare the quality of life, safety, and efficacy of gemcitabine plus cisplatin (GCis) and gemcitabine plus carboplatin (GCb) therapies in patients with urothelial carcinom Methods: Between June 2013 and March 2016, 120 urothelial carcinoma patients received two courses of first-line chemotherapy were enrolled. We prospectively evaluated quality of life (QOL) using the QLQ-C30 questionnaire on days 1, 3, and 15 in each cycle, and used QOL differences before and after chemotherapy as the primary endpoint. Secondary endpoints included, toxicity, safety, weight loss, renal function decline, immune cell responses, and tumor responses. Results: Of 120 patients, 100 patients completed QOL questionnaires. Numbers of patients for QOL analyses in GCis and GCb groups were 43 and 57, respectively. The mean age was significantly greater in the GCb group. Significantly worse appetite loss, role, constipation, nausea/vomiting, and physical scale scores were observed in the GCis group. In immune cells responses, lymphocytes and cytotoxic T cell recovery was observed in the GCb group. Neutrophil-to-Lymphocyte ratio (NLR) significantly decreased in the GCb group. No significant differences in tumor responses were identified between the groups. Conclusions: Both GCis and GCb regimens were safe and active and were free of severe adverse events. However, the GCb regimen may be associated with a better QOL status and immune cell responses. Clinical trial indentification: This study was registered as a clinical trial: UMIN000020784 Legal entity responsible for the study: Hirosaki University Funding: The Japan Society for the Promotion of Science Disclosure: All authors have declared no conflicts of interest. 280P The study of drug resistant in bladder cancer and its modulation by phytochemicals J.R. Zhuo Pathology, National Defense Medical Center, Taipei, Taiwan Background: Bladder cancer is one of the top ten most frequent cancers and over 50% patients usually experience tumor recurrence. Drug resistance (DR) is the most common cause of treatment failure and obstacle to gemcitabine (GCB) therapy clinically. Phytochemicals are considered as therapeutic agents in downregulatingthe DR in cancer. Hence, we supposed that phytochemicals could overcome and prevent the DR of urothelial cell carcinoma (UCC). Methods: GCB-DR UCC cells were obtained by long-term culture of UCC cells, T24 under low concentration of GCB. The drug tolerability of GCB-DR cells was confirmed by MTT assay. The DR-related (ABC families) and apoptotic pathways (caspase-3, bcl2, and cleaved PARP) were elucidated by Q-PCR, western blot, and flow cytometric methods individually. Subsequently, the effect of various phytochemicals on the GCB-DR cells were elucidated by MTT assay first, and related signal pathway changes were clarified using Q-PCR, western blot, and flow cytometric methods. Volume 27 | Supplement 9 | December 2016 Results: We successfully cultured GCB-resistant UCC cell line, T24-GCB and verified drug sensitivity to GCB by the MTT assay in which the half-maximal inhibitory concentration (IC50) was higher than parental T24 cells (157.1 6 25.2 vs 0.4 6 0.4 nM, p < 0.01). We found mRNAs performance of ABCC2 was increased (1.88 60.49 fold, p ¼ 0.065) but ABCB1 (0.01 6 0.01 fold, p < 0.01) was conversely significant decreased in T24-GCB cells by Q-PCR method. We found drug-resistance protein expressions were similar to mRNA expressions, ABCC2 was significant increased (1.12 6 0.03 fold, p < 0.05) but ABCB1 (0.20 6 0.09 fold, p < 0.01) was conversely significant decreased in T24-GCB by western blot method. The GCB IC50 was steady in variant passage (p1, 157.1 6 25.2; p42, 168.3 6 1.0 nM, p ¼ 0.48) of GCB exposed T24-GCB cells. The cytotoxicity of T24-GCB cells was enhanced in quercetin 10 lM (25.4% 6 4.0% vs 20.7% 6 3.5%, p < 0.01) and 30 lM (20.7% 6 3.4% vs 8.0% 6 1.0%, p < 0.01) treatment when compared with T24 cells. Conclusions: GCB-DR was caused by upregulating of ABCC2, and quercetin could enhance the cytotoxicity in T24-GCB cells. But the underlying mechanisms of cytotoxicity enhanced by quercetin, downregulation of ABCB1 mRNA and protein, and combination efficacy of GCB with quercetin in T24-GCB cells need to be evaluated in further studies. Legal entity responsible for the study: N/A Funding: Tri-Service General Hospital Disclosure: All authors have declared no conflicts of interest. 281P Adrenal tumor and its successful management; a chinese experience & report K.J. Kunwar, P. Adhikari, Z. Fuqing Urology, Wuhan Union Hospital (of Tongji Medical College of HUST), Wuhan, China Background: With the advancement in imaging modalities, adrenal tumor is commonly encountered in outpatient clinics. The treatment for benign tumor and small size tumor can be deferred with close follow up, but large tumors, due to there being higher chance of adrenocortical carcinoma & clinically problematic pheochromocytoma, need definite surgical treatment. Minimally Invasive adrenalectomy has definitely an edge over other modalities of treatment. Therefore this study summarized the outcome of surgical treatment for adrenal tumor Methods: A restrospective study was done of those who underwent adrenalectmy [Open (Group-I) and laparoscopic (Group-II) along with 1 year follow up. The main area of focus was surgical outcome, complications, patients status after 1 year post treatment. The following parameters were also evaluated; size, operative time, blood loss, analgesics, oral intake, mobilization & hospital stay. Comparable findings were tabled. Results: A total of 125 adrenalectomy (Open & Laparoscopic) was successfully completed with the average tumor size: Group-I: 4.5cm (3-10) and Group-II: 3.2cm (28), duration of the operation (112 6 28 min vs 87.1621 min, p < 0.01), blood loss (100.8.8631 ml vs 43624 ml, p < 0.01), analgesics (5.3260.49 vs 3.1660.5 days, p < 0.01), ambulation (1.5460.54 vs 1.160.30 days, p < 0.01), oral intake (2.160.60 vs 1.0860.57 days, p < 0.01), hospital stay: (8.362.8 vs 4.6 6 1.04 days, p < 0.01). On one year follow up, CT scan revealed no recurrence of tumor and no mortality is reported. Table: 281P Patients (n) Age (Mean) Size Operation time Blood loss Oral-intake Anelgesics Ambulation Hospital stay GROUP-(I) open Adrenalectomy GROUP-(II) Minimally Invasive 25 45.2 4.5cm(3-10) 112 6 28 100.8 6 31 2.1 6 0.60 5.32 6 0.49 3.54 6 0.78 8.3 6 2.8 100 39.06 3.2cm(2-8) 87.1 6 21 43 6 24 1.08 6 0.57 3.16 6 0.5 1.1 6 0.30 4.6 6 1.24 P VALUE p < 0.01 p < 0.01 p < 0.01 p < 0.01 p < 0.01 p < 0.01 Conclusions: Proper pre-operative work up to make an uneventful peri-operative and post-operative period is the basic foundation for successful adrenalectomy. With experience hemorrhage can be minimized, hemodynamic instability can be tackled and the large size of the tumor is not a contraindication for the selection of the laparoscopic approach. Thus, Minimally invasive adrenalectomy is safe, effective and can be termed as the gold standard in the treatment of adrenal tumor. Legal entity responsible for the study: N/A doi:10.1093/annonc/mdw583 | ix87 abstracts Funding: N/A Disclosure: All authors have declared no conflicts of interest. 282P Clinico-pathological characteristics and outcome in recurrent renal cell carcinoma P. Tiwari1, L. Kumar1, G. Singh2, S. Thulkar3, A. Seth4 Medical Oncology, All India Institute of Medical Sciences, New Delhi, India, 2 Pathology, All India Institute of Medical Sciences, New Delhi, India, 3 Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India, 4 Urology, All India Institute of Medical Sciences, New Delhi, India Annals of Oncology 284P Clinical outcome of the treatment for residual masses after chemotherapy for metastatic germ cell tumors R. Jikuya1, A. Hashizume2, T. Tatenuma1, N. Mizuno3, K. Muraoka4, M. Kawai2, A. Takizawa4, T. Kishida1 1 Urology, Kanagawa Cancer Center, Yokohama, Japan, 2Urology, Kimitsu Chuo Hospital, Chiba, Japan, 3Urology, Yokohama Sakae Kyosai Hospital, Yokohama, Japan, 4Urology, International Goodwill Hospital, Yokohama, Japan 1 Background: Recurrences in renal cell cancer (RCC) affects approximately one-third of patients after curative nephrectomy. However, studies from Indian subcontinent are scarce. We retrospectively analysed data of patients suffering from RCC over last one decade to find relapse rate and pattern in Indian cohort from our centre. Methods: All patients with RCC who underwent nephrectomy from 2004 to 2013 at our centre were included. Recurrence free survival (RFS) was calculated from date of surgery to date of recurrence or death. Cox Regression Model (Univariate and multivariate) was applied to identify significant prognostic factors. Results: Overall 292 patients were included in the analysis. Median age was 50 years (range-19 to 84 years). Male: female ratio was 3:1. Radical and partial nephrectomy were performed in 275(94.2%) and 14(4.8%) patients respectively. Clear cell was most common histological subtype (72%). T1, T2, T3 and T4 stage were detected in 89(30.7%), 86(29.8%), 105(36.2%) and 12(4.2%) patients respectively. One hundred and thirty six patients (46.6%) had recurrence. Eighty six patients (61.8%) relapsed at distant sites, 14(8.82%) patients relapsed at loco-regional site whereas 36 (25%) had both distant and loco-regional recurrence. Median time to develop recurrance was 18 months. Approximately 19% patient had disease reappearance after five year. Factors predicting Shorter RFS in multivariate analysis were weight loss (P ¼ 0.004), Fuhrman grade 3 or 4 (P < 0.0001), Presence of necrosis (P < 0.0001) and higher tumor stage (P ¼ 0.005). Conclusions: Compared to previous studies, our patients had higher rates of recurrence in general and loco-regional recurrence in particular. However, predictive factors remain similar. Legal entity responsible for the study: All India Institute of Medical Sciences Funding: N/A Disclosure: All authors have declared no conflicts of interest. 283P Treatment outcomes and toxicity of sunitinib in advanced renal cell carcinoma patients N.M. Saied, Z.M. Abdelhafeez, M.M. Ezz Eldin, N.A. Mosalam Oncology, Ain Shams University Faculty of Medicine, Cairo, Egypt Background: Between November 2012 and December 2014, 30 patients with histologically confirmed advanced renal cell carcimona (RCC) were treated with sunitinib at Ain Shams Clinical Oncology Department. Medical records were retrospectively reviewed for clinicopathologic characteristics such as age, sex, histology, Eastern Cooperative Oncology Group (ECOG) performance statussites of metastasis, laboratory findings, tumor progression and patient survival. Any Eastern Cooperative Oncology Group (ECOG) performance status was permitted. Both treatment schedules were included. Each patient was classified according to the Memorial Sloan–Kettering Cancer Center (MSKCC) risk scoring system . Methods: Thirty patients were enrolled in the study; aged 25 years or older. All patients received oral sunitinib 50 mg per day on a 4-weeks-on–2-weeks-off schedule or on 2weeks on 1 week off schedule. Safety was assessed regularly. Tumour measurements were scheduled per local practice. Results: A total of 30 patients received sunitinib. Median treatment duration and follow-up were 8 and 13 months. Objective response rate was 34%. Median progressionfree survival (PFS) and overall survival (OS) were 9 months and 11months . Median PFS in subgroups of interest: aged 60 years (20%), 8 months; compared to 10 months in age group 60 years. Eastern Cooperative Oncology Group performance status 0 or 1 (80%), 10 months;compared to 5.5 months in patients with ECOG 2 or 3. LN metastases (40%), 11 months and 8 months in patients with no LN metastasis. The most common grade 3/4 treatment-related adverse events were fatigue (13%), hand and foot syndrome, and anemia (each7%), diarrhea and nausea (each 3%). Conclusions: Final analysis of the sunitinib reterospective study provided a good opportunity to evaluate the long-term side effects of a tyrosine kinase inhibitor used worldwide in mRCC. Efficacy and safety findings were consistent with previous results. Legal entity responsible for the study: Ain Shams Oncology Department Funding: Ain Shams Oncology Department Disclosure: All authors have declared no conflicts of interest. ix88 | abstracts Background: For advanced germ cell tumor (GCT), chemotherapy combined with resection of residual mass is recommended to achieve long term disease free survival. However, surgery for the residual mass was often difficult, and some cases were observed without surgery. The objective of this retrospective study was to assess the clinical outcome of metastatic germ cell tumor with residual mass after chemotherapy in our hospital. Methods: From 1989 to 2016, 119 patients of metastatic germ cell tumor had been treated with chemotherapy. In this cohort, 72 patients who had residual tumors after chemotherapy were followed for up to 26 years (median; 64 months). Generally patients underwent chemotherapy until tumor marker became negative, then we followed our policy; 1) For seminoma, we observed residual masses irrespective of their size 2) For non-seminoma a) residual mass under 2cm were observed, b) residual mass over 5cm were performed extirpation, c) residual mass 2-5cm; extirpation were considered depending on the presence of teratoma component or rate of shrinkage after chemotherapy. Results: Of 72 patients 16 were pure seminoma, 56 were nonseminoma and 18 were nonseminoma with teratoma. Twenty one were IGCCC good, 28 were intermediate and 23 were poor. After chemotherapy tumor marker was positive in 5 patients. Forty seven had residual tumors in retroperitoneal lymph node (RPLN), 2 in lung, 5 in mediastinum lymph node, 7 in RPLN and lung, 4 in other lesion. After chemotherapy 36 were observed, 24 underwent RPLND and 12 underwent other surgery. Six in 36 observed patient had relapses (17%). Among them, 3 patients died of disease but other 3 were treated with additional chemotherapy and were alive without disease. Pathological diagnosis of 36 patients who received surgery were cancer in 12, teratoma in 8 and no viable cell in 16. Nine in 36 who received surgery had relapse (25%). Among them, 4 were died of disease (1 with cancer, 1 with teratoma, 2 with no viable cell). Conclusions: Our conservative policy resulted in long term disease specific survival. Although some patients may omit the residual mass resection, long term careful follow up will be necessary. Legal entity responsible for the study: Kanagawa Cancer Center Hospital Funding: Kanagawa Cancer Center Hospital Disclosure: All authors have declared no conflicts of interest. 285TiP DANUBE: A Phase 3 randomised study of first-line durvalumab (MEDI4736) 6 tremelimumab vs standard of care (SoC) chemotherapy (CT) in patients (pts) with Stage IV urothelial carcinoma (UC) S.H. Park1, D. Castellano2, D.P. Petrylak3, M.D. Galsky4, M.S. van der Heijden5, Y. Loriot6, O. Ogawa7, W-P. Su8, W. Huang9, W. Levin9, S. Ferro9, Y. Ben9, J. Bellmunt10, T. Powles11 1 Department of Medicine, Samsung Medical Center, Seoul, Republic of Korea, 2 Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain, 3Department of Medicine, Yale University, New Haven, CT, USA, 4 Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA, 5Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands, 6Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France, 7Department of Urology, Kyoto University, Kyoto, Japan, 8Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, 9Global Medicines Development, AstraZeneca, Gaithersburg, MD, USA, 10Bladder Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA, 11Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK Background: Standard first-line treatment options for metastatic UC (cisplatin-based CT or carboplatin-based CT for cisplatin-ineligible pts) are associated with suboptimal long-term outcomes. New first-line therapies are urgently needed. Immune checkpoint blockade is a promising anticancer strategy that has shown activity in CT-resistant UC. Targeting both programmed cell death-1 (PD-1) and cytotoxic T-lymphocyteassociated antigen-4 (CTLA-4) checkpoints may provide for non-redundant pathway blockade and potential additive or synergistic effects. Durvalumab is a selective, highaffinity, engineered human IgG1 mAb that blocks programmed cell death ligand-1 (PDL1) binding to PD-1 and CD80. Tremelimumab is an anti-CTLA-4 lgG2 kappa mAb. In a Phase 1/2 study (NCT01693562), single-agent durvalumab showed preliminary evidence of activity across multiple tumour types, including UC. Manageable tolerability was reported in a Phase 1b study of durvalumab and tremelimumab Volume 27 | Supplement 9 | December 2016 Annals of Oncology combination regimens in advanced NSCLC, with clinical activity observed in patients with high and low/no tumour PD-L1 expression (NCT02000947). Trial design: DANUBE is a randomised, open-label, multicentre, global Phase 3 study (NCT02516241) assessing durvalumab 6 tremelimumab vs SoC CT in treatment-naı̈ve pts with unresectable and/or metastatic UC. Pts will be randomised 1:1:1 to durvalumab 1500 mg i.v. q4w for up to 12 months; durvalumab 1500 mg i.v. q4w þ tremelimumab 75 mg i.v. q4w for 4 doses, followed by durvalumab 1500 mg i.v. q4w for up to 12 months; or SoC (cisplatin þ gemcitabine or carboplatin þ gemcitabine) for up to 6 cycles (stratification factors: cisplatin eligibility, PD-L1 expression and visceral metastasis). The primary endpoint is investigator-assessed progression-free survival (RECIST v1.1). Secondary endpoints include overall survival; proportion of pts alive and progression free at 12 months, objective response rate, duration of response and disease control rate using investigator assessment; time to second progression; healthrelated quality of life; pharmacokinetics; immunogenicity; and safety and tolerability. Recruitment is ongoing. Clinical trial indentification: NCT02516241 Legal entity responsible for the study: AstraZeneca PLC Funding: AstraZeneca Volume 27 | Supplement 9 | December 2016 abstracts Disclosure: D.P. Petrylak: Consulting/Advisory/Travel/Accommodation/Expenses/ Honoraria: Bayer, Bellicum Pharmaceuticals, Dendreon, Sanofi, J&J, Exelixis, Ferring, Medivation, Pfizer, OncoGenex, Progenics, Millennium, Celgene. M.D. Galsky: Consulting/Advisory: AZ, Genentech Research funding: BMS, Merck. M.S. van der Heijden: Consulting/Advisory: AZ/Medimmune, Roche/Genentech, Astellas, Bayer (paid to institute) Research funding: Astellas Pharma (Institute) Travel/ Accommodation/Expenses: MSD, Astellas. Y. Loriot: Honoraria: Astra Zeneca, Astellas, Roche, Janssen, Sanofi Consulting or advisory: Astra Zeneca, Astellas, Roche, Research funding: Astellas, Sanofi Travel, accommodations, expenses: Astellas, Roche, Sanofi. W. Huang: Employment: AstraZeneca Stock: AstraZeneca. W. Levin: Employment: AstraZeneca. S. Ferro: Employment: AstraZeneca Stock/Ownership: Amgen. Y. Ben: Employment: AstraZeneca Stock/Ownership: AstraZeneca. J. Bellmunt: Employment: Dana Farber Cancer Institute Honoraria: paid consultancy/adboard for AstraZeneca, Pfizer, Novartis, Genentech and Merck Research funding: Takeda, Novartis and Sanofi Travel/Accommodation: Expenses: Pfizer and Pierre Fabre. T. Powles: Honoraria: Roche/Genentech, Novartis, BMS Consulting/Advisory: Roche/Genentech; Novartis; BMS; Merck Research Funding: AZ; Roche/Genentech, GSK. All other authors have declared no conflicts of interest. doi:10.1093/annonc/mdw583 | ix89 Annals of Oncology 27 (Supplement 9): ix90–ix93, 2016 doi:10.1093/annonc/mdw584 Conclusions: ENZ showed significant efficacy over PL and was generally well tolerated. As the difference in PK in this study vs other studies is small and not clinically relevant, ENZ 160 mg dosing is appropriate in the Asian population. The trial was stopped early as it reached its primary objective. Clinical trial indentification: NCT02294461 Legal entity responsible for the study: Astellas Pharma, Inc. Funding: Astellas Pharma, Inc. Disclosure: Y-S. Pu: The author declares that Astellas Medical Inc. sponsored the clinical research. S. Yamada: The author declares that they own stocks in, and are an employee of, Astellas Pharma Inc. All other authors have declared no conflicts of interest. Genitourinary tumours, prostate 286P Efficacy, safety and pharmacokinetics (PK) of enzalutamide (ENZ) vs placebo (PL) in chemotherapy-naı̈ve patients (pts) with progressive metastatic castration-resistant prostate cancer (mCRPC): An Asian multinational study abstracts D. Ye1, H. Ahn2, Y-S. Pu3, W. Han4, L-P. Xie5, S-P. Huang6, H-C. Wu7, L. Ma8, J. Qi9, F. Zhou10, G. Sun11, L. Chen12, B. Xue13, S. Yamada14, M. Saito15, K. Suga16, Y. Sun17 1 Urology, Fudan University, Shanghai Cancer Centre, Shanghai, China, 2 Urology, University of Ulsan Asan Medical Centre, Seoul, Republic of Korea, 3 Urology, National Taiwan University Hospital, Taipei, Taiwan, 4Urinary, Hunan Cancer Hospital, Hunan, China, 5Urology, The First Affiliated Hospital of Medical School of Zheijiang University, Zheijiang, China, 6Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, 7Urology, China Medical University Hospital, Taichung, Taiwan, 8Urology, Peking University Third Hospital, Beijing, China, 9Urology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China, 10Urology, Sun Yat-sen University Cancer Centre, Guangdong, China, 11Urology, The Second Hospital of Tianjin University, Tianjin, China, 12Urology, 307th Hospital of Chinese People’s Liberation Army, Beijing, China, 13Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China, 14Biostatics Group, Japan-Asia Data Science, Astellas Pharma Inc., Tokyo, Japan, 15Clinical Pharmacology, Astellas Pharma Inc., Tokyo, Japan, 16Japan/Asia Clinical Development/Global Development, Astellas Pharma Inc., Tokyo, Japan, 17Urology, Changhai Hospital, Shanghai, China 287P Metronomic cyclophosphamide in metastatic castrate resistant prostate cancer: Experience from a tertiary cancer care center D. Dabkara, S. Ganguly, J. Ghosh, P. E, B. Biswas Medical Oncology, TMC - Tata Medical Centre, Kolkata, India Background: In PREVAIL, pts with progressive mCRPC had significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) on ENZ vs PL (Beer TM et al, N Engl J Med, 2014). The efficacy, safety and PK of ENZ vs PL were evaluated in a similar patient population in China, Taiwan and South Korea. Methods: Pts with asymptomatic/mildly symptomatic progressive mCRPC were randomised 1:1 to ENZ (160 mg/day) or PL. Interim results are presented. The primary end point was time to prostate-specific antigen (PSA) progression. Secondary end points were OS (randomisation to death) and rPFS (randomisation to radiographic progression or death). Safety and PK (pts in China only) were also assessed. Results: 409 pts were randomised; 209 ENZ/200 PL, with similar baseline characteristics. Median time to PSA progression was 7.5 months for ENZ vs 2.9 for PL (hazard ratio [HR] 0.36; 95% confidence interval [CI] 0.27, 0.50; p < 0.0001). Median OS was not yet reached (NYR) for ENZ and PL (HR 0.35; 95% CI 0.17, 0.70; p ¼ 0.0021). Median rPFS was NYR for ENZ and 4.7 months for PL (HR 0.28; 95% CI 0.19, 0.42; p < 0.0001). Median time on treatment was 6.6 months for ENZ; 3.7 for PL. Slightly more ENZ than PL pts reported 1 treatment-emergent adverse event (TEAE) [84.7% vs 80.5%]. More PL than ENZ pts reported 1 serious TEAE (24.5% vs 17.2%); grade 3 TEAE (29.5% vs 24.4%) and TEAE leading to treatment discontinuation (17.0% vs 12.9%). Seventeen pts were evaluable for PK analysis of ENZ, metabolite 2 (M2), and ENZ þ M2 after single and multiple doses of ENZ (Table). Background: Many agents have showed survival advantage in metastatic castrate resistant prostate cancer (mCRPC). Despite this improvement survival is poor, especially in subgroup of elderly patients who are not fir for cytotoxic chemotherapy. Small published reports have showed activity of oral cyclophosphamide in mCRPC in this setting. Methods: This is a single institutional data review of mCRPC treated between December’12 and May’16 with oral cyclophosphamide (50-100 mg/day) 6 oral prednisolone. mCRPC failed or not fit for docetaxel and/or abiraterone were included in this study. Monthly prostate-specific antigen (PSA) was monitored and toxicity of cyclophosphamide was recorded. PSA response was defined as 50% reduction from pre-cyclophosphamide value. Median follow-up was calculated from the day of starting cyclophosphamide and last date of follow-up or death, whichever is later. Results: Total 18 patients were included with median age-74.5 years (range: 59-83). Site of metastasis was bone in 15, bone and distant lymph nodes in 2 and rectum in 1 patient. Median duration of androgen deprivation was 21 months (range: 3-42.9). Precyclophosphamide treatment was docetaxel only in 2, abiraterone only in 6, sequential treatment with docetaxel and abiraterone in 5, and no cytotoxic treatment after mCRPC in 5 patients. Median cyclophosphamide exposure was 2 months (range: 0.9-13.5) after median follow-up of 5.8 months. Over all PSA response rate was 44%: 5 patients had PSA response and 3 patients had stable PSA. Median PSA progression-free-survival with cyclophosphamide was 4.7 months (range: 0.9-13.5). Five patients had durable PSA response of 9.9, 10.1, 10.5, 12.1 and 13.5 months, respectively. No grade 3 or 4 toxicity was observed with cyclophosphamide. Conclusions: Oral metronomic cyclophosphamide was found to be effective and well tolerated therapy in mCRPC after failure or not fit for docetaxel and/or abiraterone. In few patients, cyclophosphamide induced durable PSA response. This finding needs further evaluation in a prospective manner. Legal entity responsible for the study: N/A Table: 286P Day 1 n Cmax, lg/mL tmax, h AUC†, lg*h/mL Day 85 ENZ M2 ENZþM2 ENZ M2 ENZþM2 17 4.18 (1.49) 1.56 (1.59) 43.4 (10.9) 17 0.176 (0.0883) 22.6 (5.69) 2.28 (1.29) 17 4.2 (1.48) 2.62 (5.61) 45.7 (11.5) 17* 19.7 (2.87) 0.764 (0.589) 410 (69.5) 17* 14.9 (3.71) 5.69 (10.3) 309 (73) 17* 33.6 (4.84) 4.54 (9.13) 719 (108) Results are shown as arithmetic mean and arithmetic standard deviation. *n ¼ 16 for AUC parameter. † AUC calculated from 0-24 hours on Day 1 and 0 hours to the time of next dosing on Day 85. AUC, area under the curve; Cmax, maximum observed concentration; ENZ, enzalutamide; M2, metabolite 2; tmax, time after drug administration when maximum concentration is reached. C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts Annals of Oncology Funding: N/A Disclosure: All authors have declared no conflicts of interest. 288P Castration-resistant prostate cancer: Results of chemotherapy treatment in the real life practice C. Bandidwattanawong1, K. Pornchaichanakit2 Medical Oncology Unit, Department of Internal Medicine, Bangkok Metropolitan Administration Medical School and Vajira Hospital, Bangkok, Thailand, 2Internal Medicine, Bangkok Metropolitan Administration Medical School and Vajira Hospital, Bangkok, Thailand 1 Background: Thailand will be an aging society soon. More and more castrationresistant prostate cancer (CRPC) cases have been diagnosed. When TAX 327 study was published in 2004, the docetaxel/prednisolone regimen has been the standard treatment. However, the Thai Government has allowed re-imbursement for every patients since 2011. We still do not know what the outcomes are in the real-life setting. Methods: Data from written and electronic medical records of patients with CRPC diagnosed at Vajira Hospital from January 1, 2011 to December 31, 2015 were retrospectively extracted and analysed. Baseline characteristics included ages and PS at diagnosis and when CRPC developed, Gleason score at diagnosis, patterns of treatments at earlier stages and when CRPC developed and PSA when CRPC developed and subsequently after treatments of CRPC. Primary endpint was to determine the overall survival (OS). Secondary endpoints were to find out treatment tolerability, PSA response rate based on PSWG criteria and independent prognostic factors of survival benefit. We compared our results with the original TAX 327’s. Results: There were 41 CRPC cases in our cohorts. At the diagnosis of CRPC, the median age (95% CI) was 74 (66-76) and median PSA level was 127 (71-225). All of them had bone metastasis. Twenty one of them had documented Gleason score and the median was 8. Thirty seven of them had PS 0-2 and were treated with the docetaxel/ prednisolone regimen. Thirty two of the 37 patients could tolerate the recommended dose. The median cycles of treatment was 8. PSA response rates were 67.7% PR, 22.6% SD and 9.7% PD. Median survival was 15 (8–21) months. Compared with TAX 327, we found that our patients were older with higher risks (higher Gleason score at diagnosis and higher PSA level when CRPC developed). PSA response was the only prognostic factor of survival. Conclusions: In the real-life practice, CRPC cases are more severe and debilitated. The docetaxel/prednisolone regimen is tolerated in well selected cases even at extreme ages. We advocate that PCWG PSA response criteria should be used. To optimize cost and benefit, a medical oncologist should discontinue the chemotherapy, if no PSA response is observed after 3-4 cycles. Clinical trial indentification: COA 63/2559 Legal entity responsible for the study: Research Facilitation Division, Faculty of Medicine Vajira Hospital Funding: Research Facilitation Division, Faculty of Medicine Vajira Hospital Disclosure: All authors have declared no conflicts of interest. 289P The treatment outcome of metastatic prostate cancer patients treated with androgen deprivation therapy in University Malaya Medical Centre P. Yehgambaram1, A. Alip2, M. Saad2 Clinical Oncology, University Malaya Medical Center, Kuala Lumpur, Malaysia, 2 Clinical Oncology, University of Malaya Faculty of Medicine, Kuala Lumpur, Malaysia 1 Background: Androgen deprivation therapy (ADT) remains the mainstay of treatment in patients with metastatic prostate cancer. The majority of the patients will become castrate resistant within two years of ADT initiation. We studied the treatment outcome of patients with metastatic prostate cancer treated with ADT at University Malaya Medical Centre (UMMC) and evaluated the prognostic factors affecting the outcomes. Methods: Metastatic prostate cancer patients who were diagnosed and treated with ADT from January 2004 to January 2014 at UMMC were included in this study. The data was derived from both urology and oncology clinic notes. Treatment outcomes analysed were overall survival and time to prostate specific antigen (PSA) progression. Overall survival (OS) was calculated using Kaplan Meier method. Cox proportional hazards regression model was used to determine the factors influencing the time to PSA progression and overall survival. Log rank test was performed to assess the differences between the groups. Results: One hundred seventy six patients were included in this study and they had a median follow of 36months. The median time to PSA progression was 17months (95% Confidence interval [CI] 13.3 – 20.7) and median OS after ADT initiation was 50months (95% CI 41.4 -58.6) respectively. The median nadir PSA was 1.44ng/ml and the median time to PSA nadir (TTPN) was 9months. In multivariate analysis, presence of visceral metastasis, initial PSA of 100-500ng/ml and >500ng/ml, nadir PSA>4ng/ml and time to PSA nadir <6months independently predicted shorter time to PSA Volume 27 | Supplement 9 | December 2016 progression (p < 0.05). Furthermore, high disease burden and TTPN < 6 months as well as presence of visceral disease associated with poorer OS (p < 0.05). Conclusions: Visceral metastasis and shorter time to PSA nadir significantly affected time to PSA progression and led to poor survival in metastatic prostate cancer patients treated with androgen deprivation therapy in UMMC. Legal entity responsible for the study: University Malaya Medical Centre Funding: University Malaya Medical Centre Disclosure: All authors have declared no conflicts of interest. 290P Initial outcome of definitive intensity modulated RT in treatment of bone oligometastatic prostate cancer X. Qi, X-S. Gao, H.Z. Li, S.B. Qin, M. Zhang, X.M. Li, Q.G. Wang, X.Y. Li, M.W. Ma Radiation Oncology, 1st Hospital Beijing University, Beijing, China Background: The aim of this study was to evaluate the PSA response rate, biochemical relapse-free survival, and toxicity in bone oligometastatic prostate cancer patients who had undergone definitive intensity modulated radiotherapy (IMRT) for both primary tumor and all metastatic lesions. Methods: From 10/2011 to 9/2015, 22 prostate cancer patients with bone oligometastases (no more than 5 metastatic lesions) were treated. Metastatic lesions were documented by positive bone scan or CT scan or MRI. All patients received IMRT, 40-76Gy in 10-38 fractions (median dose: 60Gy) to metastatic lesions, 45-46Gy to the whole pelvis (for 14 patients, 63.6%) and 72-76Gy to the prostate and seminal vesicles. All patients received MAB using a LHRH agonist or orchiectomy together with an oral anti-androgen before and during RT. After RT, all patients received continuous ADT except one due to cardiovascular disease. Survival was calculated using the KaplanMeier method. Results: A total of 49 bone metastatic lesions were identified in these 22 patients. The median number of metastatic lesions per patient was 2 (range 1-5). 29 (59.1%) lesions were localized in the pelvis, 14 (28.6%) in the spines, 3 (6.1%) in the femurs and 3 (6.1%) in the ribs. The median follow-up was 17 months (range: 2-48 months). The median duration of ADT before RT was 5 months and the median pre-RT PSA was 0.7ng/ml. PSA response rate: 20 patients had a PSA decline 2 months after RT, and 13 of them decreased to < 0.1ng/ml (59.1%). The rate of biochemical relapse-free survival (bRFS) rates at 1-year and 2-year based on the nadir plus 2 ng/mL definition were 85.7% and 71.4%, respectively. 3 patients occurred biochemical failure at 2, 13 and 24 month after RT respectively. They all received the second line ADT and one of them developed lung metastases after 23 months of ADT. Additionally, no acute or late grade 3 GI or GU toxicity was recorded. Conclusions: Our study suggests that definitive IMRT is well tolerated and results in good PSA response and biochemical control in patient with bone oligometastatic prostate cancer. However, the long-term survival outcomes need to be further explored. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 291P PD-L1 over expression may predict disease aggressiveness in prostate cancer Y. Hashimoto, A. Imai, S. Hatakeyama, T. Yoneyama, T. Koie, C. Ohyama Urology, Hirosaki University, Hirosaki, Japan Background: Dramatic and long-lasting anti-tumor effects of immune checkpoint blockade has surprised the world. In the era of immunotherapy, it has been reported that tumor PD-L1 protein expression is associated with higher grade tumors and a lower survival rate for several neoplasms. It has been reported that programmed death-ligand 1 (PD-L1) expression is generally low in prostate cancer. However, no detailed investigation of this low expression has been conducted. A recent report has found that enzalutamide-resistant prostate cancer expressed high levels of PD-L1. In this study, we investigated PD-L1 expression in prostate cancer. Methods: PD-L1 mRNA expression was compared across 492 prostate cancer cases, 404 bladder cancer cases and 534 renal cell carcinoma cases based on The Cancer Genome Atlas (TCGA). Furthermore, we conducted PD-L1 immunostaining of 110 clinical samples with the SP142 assay, of which 103 were from total prostatectomy and seven were from biopsies. One hundred and five cases were diagnosed as adenocarcinoma, four as ductal adenocarcinoma, and one as signet ring cell carcinoma. Results: Comparison of PD-L1 mRNA expression based on the TCGA revealed that PD-L1 expression was significantly lower in prostate cancer than in bladder cancer and in renal cell carcinoma (p < 0.001). The SP 142 assay detected high levels of PD-L1 expression in only 2 (1.8%) cases of the 110 clinical samples. One of the cases had lung metastasis and the other had bone and lymph node metastases. Conclusions: The present study showed that PD-L1 expression is very low in prostate cancer. The SP142 assay detected PD-L1 expression in only two cases and both had doi:10.1093/annonc/mdw584 | ix91 abstracts metastatic sites. These findings suggest that there may be an association between PD-L1 expression and prostate cancer metastasis. Legal entity responsible for the study: N/A Funding: Japanese Society for the Promotion of Science Disclosure: All authors have declared no conflicts of interest. 292P Inhibition of endothelial cell-specific molecule-1 promotes the tumorigenicity and metastasis of prostate cancer cells Y-H. Hsieh Department of Biochemistry, School of Medicine, Chung Shan Medical University, Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan Background: Endothelial cell-specific molecule-1 (ESM-1) is a secretory proteoglycan comprising a mature polypeptide of 165 amino acids and a single dermatan sulfate. The ESM-1 protein has been involved in proliferation and metastatic progression in multiple tumors. The aim of this study was to evaluate the biological role of ESM-1 in prostate cancer. Methods: ESM1 expression has been determined by western blotting, qRT-PCR, and immunohistochemistry in the human prostate cell lines PC3, DU145, LNCaP, and 22Rv, and in human prostate tissue array. In this study, we identified shRNA-ESM1 to determine the role of ESM1 in prostate-cancer cell proliferation, migration, and invasion. Cell proliferative ability was measured by MTT, colony-formation, and cellcycle analysis. The role of ESM1 in prostate-cancer cell migration and invasion was analyzed by cell-migration assay and Matrigel invasion assay. The effect of ESM1 knockdown on tumorigenicity and metastasis were assessed in a subcutaneous xenograft and in vivo metastasis assay model. Results: We found that ESM1 knockdown in prostate cancer cells resulted in increased cell proliferation and colony formation ability response evidenced by decreased expression of p21 and increased expression of cyclin D1 in prostate cancer cells. Moreover, we revealed that knockdown ESM1 also induced the epithelial-mesenchymal transition (EMT), motility and invasiveness in accordance with the upregulated the MMP-9 expression, while downregulated the TIMP-1 expression. Recombinant human (Rh) TIMP-1 significantly attenuated ESM-1-mediated cell migration and invasion. Additionally, ESM-1 knockdown increased in vivo tumorigenicity and metastasis of prostate cancer cells. Conclusions: These findings provide the first evidence that the imbalance of MMP-9/ TIMP-1, is one of the regulation mechanisms by which ESM-1 promotes tumorigenicity and metastasis of prostate cancer cells Legal entity responsible for the study: N/A Funding: Chung Shan Medical Hospital, Taichung, Taiwan Disclosure: All authors have declared no conflicts of interest. 293P Serum free testosterone predicts a positive prostate biopsy in patients with PSA levels of 4-10ng/ml without any clinical findings Y. Ishizuya, T. Ujike, A. Kawashima, A. Nagahara, K. Fujita, R. Imamura, H. Kiuchi, Y. Miyagawa, M. Uemura, N. Nonomura Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan Background: Elevated PSA is the most common indication for prostate biopsy, an aggressive intervention that has become increasingly common in recent years. The incidence of unnecessary biopsy has also increased and should be avoided. However, it is a difficult decision to recommend prostate biopsy for patients who have a PSA value within the gray-zone and no other clinically suspicious findings, as no guidelines exist for this situation. Many studies have reported the utility of serum total testosterone (TT) measurement in prostate cancer screening, but these findings remain controversial. In this study, we focused on not only TT, but also serum free testosterone (FT), to investigate whether TT and FT values can predict a positive prostate biopsy. Methods: Among 218 patients who underwent prostate biopsy at our hospital from July 2014 to May 2016, we selected for this study 100 patients whose PSA values were 410ng/ml and whose digital rectal examinations (DRE) were negative. The primary endpoint was cancer detection. We assessed TT and FT values, age, PSA, prostate volume (PV), and PSA density (¼PSA/PV, PSAD) as clinical factors. Results: Forty-one patients (41.0%) were diagnosed with cancer. In univariate analysis, age and PSAD were significantly higher in the positive biopsy group compared with the negative biopsy group (p < 0.05). However, PV and FT were significantly lower in the positive biopsy group (p < 0.05). TT and PSA were not significantly different between the positive and negative biopsy groups. Multivariate logistic regression analysis revealed that PSAD and FT were independent predictors of cancer detection (p < 0.05). Subsequently, we developed a predictive model based on PSAD and FT values. Using this model, the area under the receiver-operator characteristics curve (AUC) for the ix92 | abstracts Annals of Oncology probability of detecting prostate cancer was 0.75, while the AUC for PSA was 0.61 and the AUC for PSAD was 0.70. Conclusions: In addition to higher PSAD, which is a well-known predictor, serum FT level is an independent risk factor for prostate cancer detection, whereas serum TT is not. These results can assist clinicians in deciding whether prostate biopsy should be carried out. Legal entity responsible for the study: Osaka University Graduate School of Medicine Funding: Osaka University Graduate School of Medicine Disclosure: All authors have declared no conflicts of interest. 294P Over diagnosis of prostate cancer in Eurasian men by PSA and PHI: example of heterosis Y. Xie1, E.E. Iskakova2, Q. Yang1, N. Sakenova1, Y. Chen3, Z.T.H. Tse4, Y. Huang5, S. Wu5 1 Department of Biology, Nazarbayev University, Astana, Kazakhstan, 2Module of Pathological Anatomy, Kazakh National Medical University, Astana, Kazakhstan, 3 Engineering, Vanderbilt University, Nashville, TN, USA, 4College of Engineering, University of Georgia, Athens, GA, USA, 5Department of Urology, Shenzhen University Luohu Hospital; Shenzhen Following Precision Medical Research Institute, Luohu Hospital Group, Shenzhen, China Background: Prostate-Specific Antigen (PSA) and prostate health Index (PHI) which combines PSA, free PSA and p2PSA has been applied in clinics but the accuracy in Kazakhstan patients are largely unknown. Due to long history of migration between Asia and Europe, Kazakhstani men may have the heterosis genetic background and super elevation of PSA or PHI which may not be linked to cancer. Methods: We recruited 222 male aged 50-66 to test PSA levels in 2015 in Kazakhstan. Chi-square, Pearson’s and Spearman’s correlations were calculated. Results: We found 91.45% patients showed super-high PSA levels more than 4ng/ml ranging from 4-20 ng/ml and only 8.55% patients (19 individual) showed lower PSA level ranging from 1.7 to 3.9 ng/ml. 17 patients with PSA levels less than 4ng/ml have no prostate cancer. Only 25.68% patients with PSA over 4ng/ml have cancer with Gleason score ranging from 6-8. Majority of patients (65.77%) have no cancer. Moreover, very few patients (2 cases) showed PSA lower than 4ng/ml but with cancer. PHI, the new method of detecting 3 forms of PSA, is also not correlated to adenocarcinoma (P ¼ 0.4301). In patients with PHI>27ng/ml, 87.5% patient have no adenocarcinoma; while PHI<27ng/ml, 75% patients have no adenocarcinoma. Furthermore, in prostate cancer patients (N ¼ 59), there is no significant correlation between PSA and Gleason grade (R ¼ 0.1138) confirmed by pathological biopsy. Table: 294P PSA levels in Kazakhstan patients PSA (ng/ml) Number Adenocarcinoma No cancer <4 >4 90-100 40-80 30-39 20-29 10-Jan 9 8 7 6 5 4 PHI (ng/ml) <27 >27 19 2 57 17 146 Adenocarcinoma 1 11 No cancer 3 70 5 5 4 5 27 13 14 24 28 32 43 Number Conclusions: Kazakhstani men may have higher levels of PSA than 4ng/ml but no adenocarcinoma. The PSA and PHI screening generated false positive rate is much higher than the correct positive diagnosis. In this cohort study, it is estimated that only one quarter of patients can get benefit from the PSA screening to predict the cancer. Heterosis in Eurasian men but not cancer might be related to the hyper-expression of PSA which causes the large scale over diagnosis. Our data suggest that unique diagnosis markers are urgently need for predication and avoiding biopsy for Eurasian men. Legal entity responsible for the study: Elzira E. Iskakova Funding: N/A Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology 295P 296P High dose rate (HDR) brachytherapy for prostate cancer in the early stages M. Bobkov The Second Radiotherapy Dept., Tula Regional Oncological Dispensary, Tula, Russian Federation Background: The treatment of prostate cancer in the early stages by surgical methods may not be performed in all patients. In this case, we can use a highly innovative method of radiotherapy of prostate cancer - HDR brachytherapy. Methods: Selection of patients for HDR brachytherapy was carried out in accordance with the following criteria: - A form of localized prostate cancer (T1-3N0M0); - Serum PSA levels at the time of selection to less than 20 ng/ml; - The volume of the prostate prior to treatment of less than 50 cm3; - Gradation by Gleason score 7 or less; - The absence of severe bladder outlet obstruction of the urinary tract (the volume of residual urine less than 50 ml); - The absence of a history of severe comorbidity, is a contraindication to the conduct of anesthesia. Results: During the use of HDR brachytherapy techniques in prostate cancer 40 patients were treated at Tula Regional Oncology Center. Total 54 brachytherapy session werecompleted. The average age of patients was 67 years (min - 56 years, max - 79 years). Clinically significant complications of brachytherapy were reported in 2 patients: 1 case (2.5% of the total number of patients) - long-term gross hematuria with symptoms of acute cystitis and urethritis; in 1 case (2.5% of the total number of patients) - an acute urinary retention. The average length of stay of patients treated by brachytherapy was 12 bed-days. During follow up biochemical recurrence was observed in 1 (2.5% of the total) of the patients - the PSA 3.78 ng/ml in August 2016, nadir 1.89 ng/ml. Conclusions: 1. Prostate cancer is one of the most important medical and social problems. 2. Brachytherapy is an innovative prostate cancer treatment and one of the most effective methods of treatment. 3. The use of brachytherapy of prostate cancer in Tula Regional Oncology Center proved to be economically more viable compared with external beam radiation therapy by reducing the length of stay of the patient in the hospital. 4. 97.5% of patients treated in Tula Regional Oncology Center by HDR brachytherapy recorded no biochemical (based on PSA) or local (for MRI) recurrence. Legal entity responsible for the study: Tula regional oncology disp. Funding: Tula regional oncology disp. Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 Efficiency of intermittent androgen blockade in patients with advanced prostate cancer M.N. Tashmetov1, S.K. Yusupov2 Oncology, Tashkent Medical Academy, Tashkent, Uzbekistan, 2Oncology, City Oncology Centre, Tashkent, Uzbekistan 1 Background: One of the methods to prevent the development of hormone-resistant prostate cancer (PC) is intermittent androgen blockade (IAB). The concept of IAB is in a temporary androgen blockade, in which stem tumor cells are partially preserved. When a certain response is achieved, antiandrogen therapy is stopped to allow the growth of new clones of androgen-sensible cancer cells. Then treatment is resumed. The mechanism of this method is based on the activity of the remaining stem tumor cells, which cause the growth of androgen-dependent colony, receptive to re-hormonal treatment. Methods: The study included 235 patients with advanced prostate cancer who were treated at the City Cancer Center, Tashkent city. Patients were divided into 2 groups: group 1 (n ¼ 49) – patients underwent surgical castration; group 2 (n ¼ 186) - patients received combined hormone therapy. All patients from group 2 were treated in the mode of intermittent therapy with - LHRH agonist - goserelin acetate 3.6 mg in the form of a depot injection 1 time per month and the injection form of cyproterone acetate 300 mg 2 times a month in combination with bisphosphonates. Results: The study included 235 patients with advanced prostate adenocarcinoma. In group 1 (n ¼ 49), where patients received orchiectomy, the average age of patients was 77.08 6 1.12 years. In 18 patients (36.7 6 6.88%) the prevalence of tumor process was T2NxMx, 26 patients (53.1 6 7.12%) - T3NxMx, 5 patients (10.2 6 4.32) - T3NxMx. 19 patients (38.7 6 6.96%) were detected to have skeletal bone metastases, retroperitoneal and iliac lymph nodes. Conclusions: The results of our research confirm the effectiveness of hormone therapy IAB in comparison with the traditional method of surgical castration. Our certain methods of selecting the optimal mode of hormonal therapy, depending on prognostic factors has led to improved health outcomes and quality of life of patients with advanced prostate cancer. Herewith, determination of the period of the second cycle start of hormone therapy is decided individually for each patient based on the PSA level before treatment and on the extent of tumor spread, dynamics of clinical symptoms, tolerance to androgen blockade. Legal entity responsible for the study: Yusupov Sherali Khasanovich Funding: Tashkent city oncology dispanser Disclosure: All authors have declared no conflicts of interest. doi:10.1093/annonc/mdw584 | ix93 Annals of Oncology 27 (Supplement 9): ix94–ix103, 2016 doi:10.1093/annonc/mdw585 Gynaecological cancers 297O Stratifying ovarian cancer based on AXL signaling for therapeutic targeting R.Y-J. Huang1, J. Antony1, T.Z. Tan1, J. Low2, M. Choolani3, J.P. Thiery1 Cancer Science Institute of Singapore, Singapore, 2Gynaecologic Oncology, National University Cancer Institute, Singapore, 3Obstetrics & Gynaecology, National University of Singapore, Singapore abstracts 1 Background: Ovarian cancer (OC) is a complex disease demonstrated by the heterogeneity in gene expression molecular subtypes (GEMS). Kinome enrichment analysis identifies a receptor tyrosine kinase (RTK) AXL as a top-ranking kinase in the EMT-driven, poor prognosis Mes GEMS. The Gas6/AXL pathway initiates a recurrent and sustained ERK response exclusively for Mes GEMS, which contributes to an increase in motility and signal amplification via extensive crosstalks with other RTKs. This inherent amplification of oncogenic signaling makes Mes GEMS more sensitive to AXL inhibition. Thus, identifying Mes GEMS OC patients by utilizing the AXL signaling network warrants further investigation. Methods: A gene signature of top 30 genes correlating with AXL was derived from the gene expression microarray analysis of 3500þ OC data points. This gene signature was further correlated with GEMS, EMT score, and patient outcomes. This AXL gene signature was further explored with the TCGA reverse phase protein array (RPPA) data to identify relevant AXL signaling nodes correlated with GEMS. The reproducibility was further validated by an independent cohort. Results: The AXL signature was found to be significantly overexpressed in Mes GEMS. The AXL signature showed positive correlation with the ovarian-specific EMT score (Rho ¼ þ0.4148, p ¼ 5.23e-65). This AXL signature correlated with overall survival (OS) with high AXL signature conferring a worse OS with a hazard ratio (HR) of 1.263 (p ¼ 0.0096) and 1.58 (p ¼ 0.003) when using the cut-off at median or lowest-highest quadrants, respectively. In addition, in OC, the AXL signature was also significantly overexpressed in the omental metastasis (p ¼ 0.0078) and in platinum-resistant relapsed tumours (p ¼ 0.0059) compared to their paired primary tumours. Analysing the TCGA RPPA data shows higher phosphorylation of MAPK in Mes GEMS (p ¼ 0.0282). The increased pERK in Mes GEMS is validated by western blotting in an independent cohort of GEMS-stratified OC samples. Conclusions: In conclusion, molecular stratification of OC by GEMS enables the identification of AXL and its related signaling network being a crucial player in Mes GEMS. Stratifying OC patients based on GEMS and AXL signaling for AXL inhibition is a rational option. Legal entity responsible for the study: National University of Singapore Funding: National Research Foundation of Singapore Disclosure: All authors have declared no conflicts of interest. 298O The clinical significance of deregulated cyclin E1 in high grade serous ovarian cancer (HGSOC) D. Aziz1, D. Etemadmoghadam2, G. Au-Yeung3, A. Muranyi4, I. Gresshoff1, M. Christie1, R.A. Hutchinson1, D. Ferraro1, S. Stanislaw4, L.A. Henricksen4, A. Tubbs4, K. Shanmugam4, D. Bowtell5, P.M. Waring1 1 Pathology, University of Melbourne, Parkville, VIC, Australia, 2Cancer Genomics, PeterMacCallum Cancer Centre, Parkville, VIC, Australia, 3Medical Oncology, Peter MacCallum Cancer Center, Melbourne, Australia, 4Medical Innovation, Ventana Medical Systems, Inc., Tucson, AZ, USA, 5Cancer Genomics and Genetics Program, Peter MacCallum Cancer Centre, Melbourne, Vic, Australia Background: Cyclin E1 protein is highly expressed in 30% of HGSOC, and while CCNE1 amplification provides a plausible mechanism in about half of cases, the driver and the clinical impact of high expression in non amplified cases is poorly understood. A possible mechanism is disrupted degradation of cyclin E1, which is normally promoted by FBXW7 and the proteasome pathway. Inactivation of FBXW7 is rarely due to mutations in ovarian cancer but is still possible due to epigenetic or enzymatic (USP28) inactivation of FBXW7 by deubiquitination of its substrates (cyclin E1). We sought to define the likely drivers and significance of deregulated cyclin E1 in 262 HGSOC samples obtained from patients enrolled in the Australian Ovarian Cancer Study (AOCS). Methods: We used tissue microarrays and VENTANA BenchMark ULTRA to perform dual ISH (19q12 probe spanning the CCNE1 gene and INSR probe as chromosome 19 surrogate) and immunohistochemistry to detect cyclin E1 (Santa Cruz), FBXW7 (Spring Bioscience) and USP28 (Sigma Aldrich). Results: Both CCNE1 amplification and USP28 expression significantly correlated to cyclin E1 expression (p < 0.0001, p < 0.0001 respectively) while FBXW7 did not (p ¼ 0.2). CCNE1 amplification and high cyclin E1 expression were both exclusive of BRCA1 mutation (p < 0.0001, 0.0070), had significant correlations with overall survival (OS, months), (28.3 vs. 45.6, P ¼ 0.028, HR 0.6; 30.9 vs. 45.6, P ¼ 0.028, HR 0.67 respectively). However, in non-amplified high cyclin E1 cases, no impact on OS and PFS was noted. Similarly, FBXW7 and USP28 had no impact on PFS. However, in the high USP28 subgroup, a statistically significant difference in OS between high and low cyclin E1 expression (33.6 vs. 55.8, HR 0.5, p ¼ 0.008) was noted. A trend towards worsened OS in low FBXW7 subgroup was reported for high vs low cyclin E1 expressers (30.9 vs. 48.5, HR 0.6, p ¼ 0.07). Conclusions: High expression of cyclin E1 in HGSOC is likely due to gene amplification as well as disrupted degradation by enzymatic inactivation of FBXW7. High expression of cyclin E1 in conjunction with CCNE1 gene amplification and/or high USP28 expression are associated with unfavorable outcomes. These findings may be of importance for targeted therapy development in HGSOC. Legal entity responsible for the study: The University of Melbourne Funding: Ventana Medical System Disclosure: D. Aziz, D. Etemadmoghadam, G. Au-Yeung, A. Muranyi, I. Gresshoff, M. Christie, R.A. Hutchinson, D. Ferraro, S. Stanislaw, L.A. Henricksen, A. Tubbs, K. Shanmugam, D. Bowtell, P.M. Waring: Ventana Medical Systems are providing funding to undertake this project 299O Genomic Signature identifying origins of EOC from Fallopian tube and ovary epithelium L-J. Di1, D. Hao1, J. Wang1, J. Li1, L. Wang2 Faculty of Health Sciences, University of Macau, Macau, China, 2Faculty of Health Medicine, University of Macau, Macau, China 1 Background: The molecular mechanism of epithelial ovarian cancer (EOC) is poorly understood. As a result, the treatment and overall survival of EOC have improved little for decades. Although large-scale genomic analyses have identified the recurrently altered pathways in EOC, the most essential knowledge about EOC, including the tissue origin, the classification of clinically associated subtypes are still largely unknown. Methods: Data retrival from public accessible database covering clinical patient tumor samples. The data include the gene expression analyzed by microarray and RNA-seq, the patient survival information, the disease prognostic information etc. The analysis of the clinical data is using standard bioinfomatic tools. The experiments were performed following standard procedures. Results: A comprehensive list of datasets covering multiple levels of genomic data have been collected to identify the tissue origin for different histological types of EOC, and confirmed that both ovary epithelium and fallopian tube accounts for the majority of EOCs. Based on the collected datasets, we also applied a meta-analytic strategy and have defined two new clinically associated subtypes of high-grade serous ovarian cancer which, coincidentally, almost equivalent to the EOC classification by tissue origin defined by genomic data. Based on these analysis, we were able to predict some target genes which show significant correlation to the risk of cancer patient and by taking advantage of phamacogenomics data, we also identified the drugs that targeting the pathways related to these genes. Preliminary experiments in ovarian cancer cell lines demonstrated the therapeutic effect of these drugs. Conclusions: To our knowledge, this is for the first time that clinical genomic data is used to analyze EOC in a perspective of establishing new genomic signatures with clinical utility and identifying novel targets to improve the treatment of EOC. This research is funded by FDCT/025/2014/A1, FDCT/088/2014/A2, MYRG2015-00037FHS, MYRG2015-00167-FHS, MYRG2016-00251-FHS. Legal entity responsible for the study: University of Macau Funding: University of Macau, and Foundation for development of Science and technology in Macau Disclosure: All authors have declared no conflicts of interest. C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts Annals of Oncology 300O Assessment of the effectiveness of cervical cancer screening 1 2 R. Gvamichava , T. Beruchashvili Screening, National Screening Center, Tbilisi, Georgia, 2Management, National Screening Center, Tbilisi, Georgia 1 Background: According to the US Center for Disease Control (CDC 2013), a reliable statistical tendency of decreasing cervical cancer incidence and mortality caused by this disease has beenrecorded in the United States over the recent 40 years that isrelated tohigh rate coverage of the female population by Pap-test screening. This tendency is proved by American Cancer Society (ACS, 2012).According to Gold M.A. (2006), 7080% decrease of cervical cancer incidence has been achieved by Pap test screening in developed countries. According to the Norwegian Cervical Cancer Screening Program (NCCSP, 2014), screening has contributed to 25% decrease of cervical cancer incidence and 50% decrease of mortality caused by this disease in Norway.According to Nanda K. et al. (2000) data, in case of cervical cancer CIN 2/3, Pap test sensitivity and specificity vary within the range 47% - 62% and 60% - 85% correspondingly. Methods: We have studied the cost-effectiveness of cervical cancer screening program, based on5 year period data (2010 – 2014): 66,324 women received gynecological examination and Pap test and 12,147 received colposcopy, targeted biopsy and morphological analysis. In 2013, 13 584 women received cervical cancer screening, among them 7,416 womenat the National Screening Center (NCC). The indicators of diagnostic effectiveness of gynecological examination, Pap test, colposcopy and combination of a Pap test and colposcopy have been studied based on NCC data with a purpose of assessment. Results: In 2013, the prevalence of cervical severe dysplasia(CIN3) and intraepithelial carcinoma (CIS) per 1,000 female population eligible for screening constituted 9,8% and cancer prevalence was 6,1%. The study has found that making of alterations in a screening guideline and re-adjusting of a target group from 25-59 to 30-64 age group will increase the number of detected cervical cancer cases and decrease needed expenditures: in case of 50% coverage of a target group by 93,000 GEL and by 130,000 GEL in case of 70% coverage. Conclusions: Making of alterations to the screening guideline and readjusting of a target group to 3064 age group will significantly enhance the costeffectiveness of cervical cancer screening. Legal entity responsible for the study: National Screening Center Funding: National Screening Center Disclosure: All authors have declared no conflicts of interest. 301O Exploring perceptions of cervical cancer in Dhaka, Bangladesh N.T. Islam1, A. Lofters2, A. Nessa3, M. Vahabi4, O. Ginsburg5, T. Ishaque6 Department of Medicine, St. Michael’s Hospital University of Toronto, Toronto, ON, Canada, 2Dept of Family and Community Medicine, St. Michael’s Hospital University of Toronto, Toronto, ON, Canada, 3Dept of Obstetrics and Gynecology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, 4Daphne Cockwell School of Nursing, Ryerson University, Toronto, ON, Canada, 5Clinical Public Health Division, Women’s College Research Institute, Toronto, ON, Canada, 6Research and Evaluation Division, BRAC University, Dhaka, Bangladesh 1 Background: The goals of this study were to assess knowledge of cervical cancer symptoms and risk factors and to identify barriers to cervical cancer screening among women being seen in a colposcopy center in urban Dhaka, Bangladesh. Methods: This was a descriptive, exploratory study. We administered an eight-question survey to 50 women at an outpatient gynecology clinic at Bangabandhu Sheikh Mujib Medical University (BSMMU), a colposcopy center in Dhaka, Bangladesh. The survey included both open-ended and closed-ended questions which assessed knowledge of cervical cancer (including risk factors, symptoms, prevention, and treatment), use of visual inspection with acetic acid (VIA) testing, and reasons for non-testing. Results: The majority of women correctly identified postcoital bleeding, irregular bleeding, and constitutional symptoms (fever, weight loss) as symptoms of cervical cancer. The majority of women also correctly identified multiparity, multiple sexual partners, early age at first intercourse, human papilloma virus (HPV), and cigarette smoking as risk factors. However, most women did not recognize lack of condom use as a risk factor for cervical cancer. The majority of women surveyed believed cervical cancer was preventable but most felt that it was not curable. Only 21 of the 50 women had previously undergone VIA testing. Of these 21 women, all stated they would return for repeat testing. Of the 29 women who had never had VIA testing, the most common barriers identified included not knowing what VIA testing was and the assumption that if a woman has no symptoms, she does not need to undergo VIA testing. Conclusions: The 50 women in this study displayed relatively strong knowledge of symptoms and risk factors for cervical cancer. However, the most common barrier to VIA testing continues to be lack of knowledge about the test itself and lack of knowledge about the use of VIA testing in primary prevention (i.e. screening is targeted at asymptomatic women). Bangladesh is in dire need of a national cervical cancer screening program to reduce mortality from this very preventable and treatable disease. Volume 27 | Supplement 9 | December 2016 Legal entity responsible for the study: St. Michael’s Hospital and Bangabandhu Sheikh Mujib Medical University (REB approval obtained from both institutions) Funding: N/A Disclosure: All authors have declared no conflicts of interest. 302PD Targeted sequencing of a specific gene panel detects a high frequency of ARID1A and PIK3CA mutations in endometrioid and clear cell ovarian cancer T-K. Er1, Y-F. Su2, C-C. Wu3, C-C. Chen4, E-M. Tsai2 Department of Laboratory Medicine, Asia University Hospital, Asia University, Taichung, Taiwan, 2Department of Obstetrics and Gynecology, Chung-Ho Memorial Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, 3 Department of Pathology, Chung-Ho Memorial Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, 4Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan, Kaohsiung, Taiwan 1 Background: Epithelial ovarian cancer is the fifth leading cause of cancer death among women with significant morbidity and mortality. Studies showed that many genetic factors play an important role in the development of epithelial ovarian cancer. The aim of this study was to assess the mutational profile in epithelial ovarian cancer using formalin-fixed, paraffin-embedded (FFPE) tumors from a Taiwanese population by performing targeted sequencing of 9 cancer-associated genes. Methods: Targeted sequencing was performed in 32 formalin-fixed, paraffin-embedded (FFPE) tumor specimens, consisting of matched paired samples from 16 epithelial ovarian cancer patients. A custom panel was designed to target 9 cancer genes. Genetic alterations in the 9 cancer-associated genes were detected using a deep sequencing (>1000X) approach. All the deleterious mutations were then reconfirmed using Sanger sequencing. Results: ARID1A, PIK3CA, and KRAS were most frequently mutated genes. Most remarkably, ARID1A mutations and PIK3CA mutations, which accounted for 56.3% and 50% of tumors, respectively. Other genes including MLH1 (6.3%) and CREBBP (6.3%) were identified in our population. Notably, we identified coexistent ARID1A- PIK3CA mutations (43.8%) and ARID1A-KRAS mutations (12.5%), respectively, in tumors. Conclusions: In summary, our study shows the feasibility of performing targeted sequencing using formalin-fixed, paraffin-embedded samples. Further studies are needed to elucidate the mechanism of chromatin remodeling and PI3K/AKT pathway to its critical role of tumor development and progression in ovarian malignancy and to investigate new cancer therapy targeting. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 303PD Genetic characterization of ovarian carcinoma patients in Taiwan C.J. Chen1, C-H. Chen1, Y-J. Lu1, K.T. Tan1, H-C. Chen1, A. Chao2, T-H. Wang2, S-J. Chen1 1 Clinical Sequencing, ACT Genomics Co. Ltd., Taipei, Taiwan, 2Obstetrics and Gynecology, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan Background: Ovarian cancer is the ninth most common cancer worldwide and the fifth most frequent cause of cancer-related deaths in women. However, therapeutic options for patients with recurrent diseases are extremely limited. This study aims to identify molecular changes that characterize the three main ovarian cancer subtypes (serous, endometroid and clear cell) and to explore genetically-guided therapeutic strategy for each subtype. Methods: 85 patients with ovarian cancer who were unselected for their family history of malignancies were included in the study. The histological subtypes included serous (n ¼ 36), endometroid (n ¼ 26), and clear cell (n ¼ 23) carcinomas. Formalin-fixed paraffin-embedded samples obtained from the primary tumor of each patient were used for genetic analysis. Mutational status and copy number of 409 cancer related genes were determined using next-generation sequencing. Results: Non-synonymous mutations and copy number alterations were detected in all tumor samples. TP53 is the most frequently mutated gene in ovarian carcinoma with more frequent occurrence in the serous (80.6%) and endometroid (61.5%) subtypes. In the serous subtype, BRCA1/2 and DNA damage repair pathway was the most commonly altered cellular pathway, occurring in 44% of the patients. Alterations in the PI3K/AKT/mTOR signaling cascade were the most commonly observed genetic aberrations detected in the endometroid and clear cell subtypes. Of which, genetic alterations of the PIK3CA (26.9% in endometroid; 39.1% in clear cell) and PTEN (26.9% in endometroid, but none in clear cell) genes are more frequently detected. Overall, alterations in actionable pathways were detected in more than 80% of tumor samples. Conclusions: Our results suggest that genetic aberrations should be taken into considerations to support the treatment selection for serous, endometroid and clear cell doi:10.1093/annonc/mdw585 | ix95 abstracts ovarian carcinoma. In addition, genetic alterations in PTEN could be used to differentiate between the endometroid and the clear cell subtypes. Legal entity responsible for the study: Shu-Jen Chen Funding: ACT Genomics Co. Ltd. Disclosure: All authors have declared no conflicts of interest. 304PD Treatment approach and prognosis of pediatric and adolescent non-epithelial malignant ovarian tumors: A retrospective prognosis analysis B. Zhang1, P. Liang2, X. Zhang1, S. Li3, G. Xu1 Gynecology and Obstetric, 2nd Affiliated Hospital Sun Yat-sen University, Guangzhou, China, 2Gynecology and Obstetric, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China, 3Gynecology and Obstetric, 1st Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China 1 Background: Non-epithelial malignant ovarian tumors are rare in the pediatric and adolescent population. Because of the rarity of the disease, few studies with a large sample size are available, and survival and prognostic factors in this specific group of patients are poorly known. Methods: This was a retrospective study of 170 girls (median age at presentation of 14 years) diagnosed with primary non-epithelial malignant ovarian tumors between 1990 and 2014 at the Sun Yat-sen Memorial Hospital and Cancer Center of Sun Yat-sen University. Symptoms, pathological data, treatments, and outcomes were obtained retrospectively from the medical records. Results: Most (85.29%) tumors occurred in patients aged 10-18 years and most cases were FIGO stage I (70.0%). The predominant pathological type was germ cell tumors (87.06%). All patients underwent surgery, and 80 (47.06%) underwent conservative incomplete staging surgery (unilateral salpingo-oophorectomy or tumor excision). The 5-year progression-free survival (PFS) was 59.2%.The 5-year overall survival (OS) was 88.7%. Surgical hospital (HR ¼ 0.388,95%CI¼0.213-0.706, P ¼ 0.002) was independently associated with PFS. Recurrence state (HR ¼ 163.26,95%CI¼1.32120181.875, P ¼ 0.038) was independently associated with OS. Conclusions: Ovarian cancers in children and adolescents have features of good prognosis. Girls who received first operation in tertiary hospitals had better PFS. Patients who did not suffer recurrence had better OS. Legal entity responsible for the study: Sun Yat-sen Memorial Hospital Funding: N/A Disclosure: All authors have declared no conflicts of interest. 305PD Clinical profile of germ cell tumor of ovary - A single centre experience S. Ganguly1, B. Biswas1, D. Dabkara1, P. E1, J. Ghosh1, J. Bhaumik2, D. Midha3 Medical Oncology, TMC - Tata Medical Centre, Kolkata, India, 2Gynaec oncology, TMC - Tata Medical Centre, Kolkata, India, 3Oncopathology, TMC - Tata Medical Centre, Kolkata, India 1 Background: Germ cell tumor of ovary (GCT) constitutes around 3% of all ovarian neoplasms. Methods: Patients with newly diagnosed ovarian GCT who were being treated in our institute from July’ 2012 to June’2016 were included in this study. Mode of presentation, histology, treatment outcomes and toxicity of the treatment were recorded. Results: Eighteen patients were treated during this time period with median age of 28 years (range 12 -51 years). Most common mode of presentation was pain abdomen (66%), followed by abdominal distension (22%). Yolk sac tumor (YST) was the most common histology in 11 patients (61%) and the stage at presentation was I in 11(61%), II in 1(0.5%), III in 4(22%) and IV in 2(11%). Two patients didn’t undergo surgery. All patients except two (stage IA dysgerminoma) were treated with chemotherapy (BEP in 13 and EP in 4). Four patients with YST had post treatment elevation of serum Alpha fetoprotein (AFP) level. Two of them had slow resolution of AFP over time. Two patients had persistently elevated AFP levels for which salvage chemotherapy was given. One patient developed grade 4 neuropathy with slow resolution of AFP level and one was lost for follow up Most common toxicity was febrile neutropenia in 9 patients (50%). Two patients developed grade 4 neuropathy. After a median follow up of 17.7 months (range 2.9-41.5 months), median progression free survival (PFS) has not been reached and 3 year PFS is 86.7%. Conclusions: Ovarian GCT is a highly curable malignancy with multimodality treatment including surgery and cytotoxic chemotherapy with acceptable toxicity. The challenges remain in limiting long-term treatment related toxicity. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. ix96 | abstracts Annals of Oncology 306PD Patterns of care of cervical cancer in the elderly: A qualitative review of all published literature B.P. Venkatesulu, S. Mallick, A.G.F. Thoyattan, G.K. Rath Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India Background: Cancer uterine cervix is the fourth most common cancer worldwide among women. However, there is limited data about elderly patients of cervical cancer and there is gross under-representation of elderly patients in clinical trials. Hence, optimal therapy of such patients is not well formulated. Methods: We conducted this systematic review of current evidence to assess age specific issues that arise in cervical cancer patients and possible ways to counteract them. Results: A total of 17338 publications are reported in PubMed till July, 2016 pertaining to cervical cancer. Out of these only 24 publications (full length paper or Meeting proceedings) reported about clinical outcome of elderly patients with cervical carcinoma. These publications report data for a long period of time and as early as 1949. In these publications, out of 14479 patients aged 60 years of age, 11279 (77.89%) received external beam radiation. Concurrent chemotherapy has been used in 11 publications. Brachytherapy usage has been reported in 19 publications. In few studies brachytherapy was not used because of fear of toxicity. Overall, Low dose rate (LDR) was the most common modality followed by High dose rate (HDR). The authors have showed technical reasons (48.7%), Comorbidities 69.4% and patient refusal (38.3%) as causes for not delivering brachytherapy. 5 year OS have been found to be inferior to the non-elderly cohort and ranges from 27%-69% for elderly compared to 58%-75% in the non-elderly population. Dismal 11% 5 year OS has been reported for patients treated with suboptimal radiation dose compared to 74% treated with chemo radiotherapy followed by brachytherapy in the elderly. Conclusions: Gross under-representation of patients above 65 years in clinical trials has resulted in treatment dilemmas in the elderly. With advent of Comphrensive geriatric assessment tools and importance of biological age, elderly cervical cancer patients should get treatment protocols similar to their adult counterparts with emphasis on toxicity limitation and enhancing quality of life by integrating newer radiation technology, biological response modifiers and targeted therapy. Legal entity responsible for the study: Bhanu Prasad Venkatesulu Funding: All India Institute of Medical Sciences Disclosure: All authors have declared no conflicts of interest. 307PD Results of high dose rate interstitial- brachytherapy in the treatment of locally advanced carcinoma cervix: A single institution experience S.D. Shamsundar, K. Aradhana, R. Nanda, B. Thejaswini, G.V. Giri, A.S. Udaykrishna, H.B. Govardhan Radiation Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India Background: Chemoradiotherapy in addition to brachytherapy plays a major role in the treatment of patients with locally advanced carcinoma cervix. However, Intracavitatory brachytherapy (ICBT) is not feasible in all patients for various reasons, and these are the patients considered for High dose rate Intestitial Brachytherapy (HDR-ISBT). The aim of this study was to report the outcome and toxicity profile of patients undergoing HDR- ISBT Methods: Between January 2009 and December 2013, 103 patients with locally advanced carcinoma cervix (International Federation of Gynecology and Obstetrics{FIGO} stage IIB-IVA), were treated with external beam radiotherapy (EBRT) of 45 to 50 Gy at 1.8 to 2 Gy per fraction over 5 to 6 weeks, along with or without concurrent chemotherapy (cisplatin). All patients received HDR-ISBT boost of 3 fractions, 6 to 7 Gy per fraction after EBRT Results: Majority of the patients belonged to FIGO stage III 68/103(66.02%), stage IIB 31/103(30.1%) and only 4/103 (3.88%) stage IVA. The most common indication for HDR ISBT was cervical os not negotiable 56/103(54.36%), followed by residual parametrial disease 33/103(32.03%), anatomy not fit for ICBT 10/103(9.70%), no documented reason 4/103(3.88%) The Median follow up was 37 months, the three year disease free survival and overall survival are 58.25% and 61.1% respectively. Grade III/IV rectal toxicity was seen in 11/103(10.67%) patients and grade III/IV bladder toxicity was seen in 5/103(4.8%) patients. The response to EBRT was the only factor affecting the survival of patients in multivariate analysis. Conclusions: Locally advanced cervical cancer patients in whom ICBT is not possible, chemoradiotherapy followed by HDR ISBT achieves good survival rates with acceptable toxicity. Legal entity responsible for the study: S.D.Shamsundar Funding: Self funded Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology 308PD Cervical cancer burden in the Radiation Oncology Unit, Mandalay General Hospital A.A. Myint1, S. Mon2, T.T. Aye2, S.S. Htay2 Radiation Oncology Unit, Mandalay General Hospital, Mandalay, Myanmar, 2 Oncology Department, Bahosi Medical Centre Bahosi Housing Complex, Yangon, Myanmar 1 Background: Mandalay General Hospital (MGH) is a 1000 bedded public tertiary care centre and serves as the main teaching hospital for the University of Medicine, Mandalay, Myanmar. Oncology services provided at MGH include medical oncology and radiation oncology. We explored the case load and studied the profile of patients with carcinoma cervix at radiation oncology unit, MGH in 2015. Methods: The Cancer Registry for MGH was interrogated and cervical cancer cases registered from January 2015 to December 2015 were then selected and a retrospective chart review was conducted. Data regarding patients’ age, parity, date of diagnosis, Staging, histological diagnosis obtained were reviewed. Summary statistics were used to describe results. Results: A total of 553 women with carcinoma cervix were identified; median age was 53.24 years (range 27 yrs- 84 years). Age under 45 were 19.3% (n ¼ 107). Regarding risk factors, 35.08% (n ¼ 194) patients were Parity 3 -5, 25.31% (n ¼ 140) were Parity 6-9, 13.20% (n ¼ 73) were Parity 0-2, 2.35% (n ¼ 13) were Parity 10-13 and missing data of 24.05% (n ¼ 133). Histopathological diagnosis reported as Squamous Cell carcinoma were 72.33% (n ¼ 400), Adenocarcinoma were 11.74% (n ¼ 65). Stage distribution were 12.2% with Stage I, 6.69% with Stage II, 58.58% with Stage III, 6.69% Stage IV and 15.57% with missing data about stage. Conclusions: Cervical cancer is the second commonest cancer among female malignancies registered in radiation oncology unit, MGH. More than half of patients with carcinoma cervix were still presented at an advanced stage and a relatively high number of patients having gave birth to three or more children were seen. Thus, health education of public awareness of cervical cancer should be extensively promoted to improve early detection and access to proper treatment to reduce cervical cancer mortality in Myanmar. Legal entity responsible for the study: Radiation Oncology Unit, MGH Funding: Radiation Oncology Unit, MGH Disclosure: All authors have declared no conflicts of interest. 309PD Features of cervical cancer in HIV-infected and uninfected women in association with human papilloma virus M.N. Tashmetov Oncology, Tashkent Medical Academy, Tashkent, Uzbekistan Background: Annually 470000 new cases of cervical cancer are registered around the world and more than 270 000 of them are fatal. According to statistical data in the Republic of Uzbekistan, it is also observed the increased cervical cancer morbidity in women, mostly of reproductive age, with an average annual growth of 1.2%. In the analysis of the incidence of cervical cancer in the city of Tashkent in the period from 2010 to 2015 it was found that the number of newly detected patients in 2010 amounted to 121 cases, but by 2015 this igure had risen to 176 cases, besides which the frequency of advanced stages of malignancies had increased. Methods: The study included 89 patients with cervical cancer associated with HPV, of them, the main group 49 (55.1%) patients were HIV-infected, and 40 (44.9%) patients were HIV-uninfected and made up the control group. Patients underwent treatment in clinic of Tashkent City Oncology Dispensary and in Republican Center of AIDS in the period from 2005-2015. Age of patients ranged from 25-70. Results: Analysis of the results of examinations and treatment of 89 (100%) patients who were at different stages of cervical cancer according to data of colposcopy, cytology, viral load of HIV revealed that among 49 HIV-infected patients, in 25 (51%) cases was found T4, in 18 (37%) patients T2-T3, and the other 6 (12%) patients had T1 stage of disease. Conclusions: The detection rate of late stages of cervical cancer (stage T4) among HIVinfected women compared with HIV-negative increased 5 times (51% and 10%, respectively). HIV-positive patients were mainly infected with both HPV 16 þ 18 (80%). The tumor process is accompanied by the development of endogenous intoxication and decrease in immune strength of cancer patients, therefore the presence in a patient of HIV infection associated with HPV can lead to rapid progression of malignant neoplasms. Legal entity responsible for the study: Tashkent Medical Academy Funding: Tashkent Medical Academy Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 310P Oral leukoplakia in women treated with long-term pegylated liposomal doxorubicin H. Nomura, M. Nagashima, M. Matoda, S. Okamoto, H. Kanao, K. Kato, K. Omatsu, Y. Sugiyama, K. Utsugi, N. Takeshima Gynecology, Cancer Institute Hospital of JFCR, Tokyo, Japan Background: Pegylated liposomal doxorubicin (PLD) is approved for the treatment of Kaposi’s sarcoma and recurrent ovarian cancer. Some case series have recently reported that long-term treatment with PLD may cause squamous cell carcinoma of the tongue and oral cavity. However, the natural history of these carcinomas is not fully understood. This study aimed to investigate changes in the oral cavity of patients treated with PLD. Methods: After approval by the institutional review board, we searched medical records and found 16 patients with recurrent ovarian cancer who were administered more than 10 cycles of PLD. In our hospital, every patient treated with PLD has an oral examination each time before the administration of PLD for the purpose of detecting stomatitis. We retrospectively reviewed the medical records of those 16 patients. Results: The median number of cycles of PLD was 13, and the median dose of PLD was 625 mg/m2. Leukoplakia, which is known as a precancerous lesion of the oral cavity, was diagnosed in six patients. Squamous cell carcinoma of the oral cavity was not observed in the patients included in our study. Among the six patients, the median number of cycles of diagnosis of leukoplakia was 16 (range, 9–19) and the median dose of PLD was 745 mg/m2. A strong tendency between the dose of PLD and leukoplakia was indicated using the Pearson correlation coefficient (0.84). Conclusions: Patients with leukoplakia of the oral cavity were found among those treated with long-term PLD administration. The proportion of leukoplakia increased in a dose-dependent manner. Squamous cell carcinoma of the oral cavity induced by PLD may be shown to arise from leukoplakia. Therefore, a periodic oral check is recommended, especially for patients who are administered more than 10 cycles of PLD, to avoid squamous cell carcinoma of the oral cavity. Clinical trial indentification: 2016-1017 Legal entity responsible for the study: Hidetaka Nomura Funding: N/A Disclosure: All authors have declared no conflicts of interest. 311P Blockade of vascular endothelial growth factor receptors by tivozanib inhibits growth and restores chemosensitivity in human ovarian carcinoma cells G. Zarrinrad, M. Momeny, Z. Sabourinejad, F. Moghaddaskho, H. Eyvani, H. Yousefi, A. Poursheikhani, F. Barghi, F. Esmaeilii, M. Yaghmaiee, K. Alimoghaddam, A. Ghavamzadeh, S. Ghaffari Hematology/oncology, HORC-SCT, TUMS-Shariati Hospital, Tehran, Iran Background: Epithelial ovarian cancer (EOC) is the most fatal gynecological malignancy worldwide. Despite initial therapeutic response, the majority of advancedstage patients relapse and succumb to chemoresistant disease. Therapy-resistant EOC is an incurable malignancy and overcoming drug resistance is the key to successful treatment. Members of vascular endothelial growth factor (VEGF) family of ligands and receptors are over-expressed in EOC and play key roles in its malignant progression though the exact contribution of this pathway in development of the chemoresistant disease remains largely elusive. Methods: Cell proliferation, colony formation and anoikis resistance assays were performed to evaluate the effects of tivozasnib on cell viability. Quantitative reverse transcription-PCR was conducted to measure the effects of tivozanib on expression of IL6, IL8, CCNB1, BIRC5, CDK1, CDK2, CHEK1, CHEK2, CDKN1A and SFN. To investigate changes in expression of WEE1, cyclin B1, CDC25C, BCL2, BAX, P21 and survivin after tivozanib treatment, Western blot analysis was done. Propium iodide staining was performed to measure cell cycle distribution and a caspase 3 activation assay was used to investigate the effects of tivozanib on induction of apoptosis. Zymoanaylsis, uPA activity assay and cell migration/invasion assays were done to explore the effects of tivozanib treatment on MMP-2 activity, uPA enzymatic levels and motility of the chemoresistant ovarian carcinoma cells. All data were evaluated in triplicate against untreated control cells and collected from three independent experiments. Data were graphed and analysed using GraphPad Prism Software 6.0 using one-way ANOVA and the unpaired two-tailed Student’s t test. All data are presented as mean 6 standard deviation (SD). Results: In this report, we showed that expression of the VEGF family members is higher in therapy-resistant EOC cells compared to sensitive ones. Over-expression of VEGFA, VEGFC and VEGFR2 correlated with dug resistance and tivozanib, a paninhibitor of VEGF receptors, reduced proliferation of the chemoresistant EOC cells through a G2/M cell cycle arrest. Tivozanib decreased adhesive and invasive potential of these cells via reduction of intercellular adhesion molecule-1 (ICAM-1) and enzymatic activity of urokinase plasminogen activator (uPA) as well as matrix metalloproteinase-2 (MMP-2). Moreover, tivozanib synergistically enhanced anti-tumor effects of EGFRdirected therapies including erlotinib, gefitinib and cetuximab via down-regulation of anti-apoptotic proteins survivin and Bcl-2. doi:10.1093/annonc/mdw585 | ix97 abstracts Conclusions: Altogether, these findings suggest that the VEGF/VEGFR pathway may have potential as an attractive therapeutic target in therapy-resistant EOC and VEGFR blockade by tivozanib may yield stronger anti-tumor efficacy and circumvent resistance to EGFR-directed therapies. Legal entity responsible for the study: Dr. Majid Momeny Funding: Tehran University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. 312P Elevated serum CA125 predicts recurrence in patients with completely resected ovarian clear cell carcinoma T. Ebata1, M. Yunokawa2, S. Bun3, E. Noguchi2, A. Shimomura2, T. Shimoi2, K. Yonemori2, C. Shimizu2, Y. Fujiwara2, T. Kato4, K. Tamura2 1 Medical Oncology, Chiba University, School of Medicine, Chiba, Japan, 2 Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan, 3 Pharmacy, National Cancer Center Hospital, Tokyo, Japan, 4Gynecology, National Cancer Center Hospital, Tokyo, Japan Annals of Oncology expression in normal epithelium was 0.5, in SCE - 2.85, in SCOUT - 2.95, in HGSC - 0.5, ALDH1 expression in normal epithelium was 0.5, in SCE - 2.91, in SCOUT - 2.92, in HGSC - 0.6. Statistically significant differences were found for all markers between normal epithelium, secretory cells changes (SCE and SCOUT) and HGSC (p < 0.05). Conclusions: We have shown that the SCE was an independent intraepithelial lesions. The frequency of SCE increase with age. The difference in frequency of SCE between patients with extraovarian pathology and HGSC was more significant than difference in frequency of SCOUT between these groups. Thus, SCE can be a more sensitive marker for the early stages of the pathogenesis of HGSC. Multiple molecular events occur in SCE and the therapeutic effect on the early stages of pathogenesis may have several points of application. Legal entity responsible for the study: Federal State Budget Institution “Research Center for Obstetrics, Gynecology and Perinatology” Ministry of Healthcare of the Russian Federation Funding: Federal State Budget Institution “Research Center for Obstetrics, Gynecology and Perinatology” Ministry of Healthcare of the Russian Federation Disclosure: All authors have declared no conflicts of interest. 314P Background: The Gynecological Cancer Intergroup has recommended that serum CA125, which is a good predictive marker for recurrence, be included in the criteria for defining response and progression of ovarian carcinoma. However, the criteria were developed on the basis of patients with serous adenocarcinoma. To assess the optimal criteria for patients with clear cell carcinoma, we investigated elevated serum CA125 and recurrence in patients with ovarian clear cell carcinoma. Methods: We retrospectively investigated the medical records of patients with ovarian clear cell carcinoma at our hospital between June 1997 and December 2014. Patients with optimally resected and histologically confirmed clear cell carcinoma in our hospital whose serum CA125 level was higher than 35 U/mL before treatment and lower after operation or adjuvant chemotherapy were included in this study. We calculated the sensitivity, specificity, positive and negative predictive values, and time between elevation and radiological recurrence. Results: One hundred and thirty nine patients were diagnosed with ovarian clear cell carcinoma during this period. Of these, 55 patients were eligible for the study, and 16 events [A1] [A2] occurred. The sensitivity and specificity of elevated serum CA125 level for predicting recurrence were 68.8% and 97.4%. The positive and negative predictive values were 91.7% and 88.4%. The median time from CA125 elevation to recurrence was 28 days (95% confidence interval: 0–51 days). Conclusions: A CA125 level above 35 U/mL was highly specific for predicting recurrence. We should consider radiological examinations for patients with clear cell carcinoma and CA125 levels over 35 U/mL. Legal entity responsible for the study: National Cancer Center Hospital Funding: N/A Disclosure: All authors have declared no conflicts of interest. 313P Secretory cells expansion as a very early event in ovarian high-grade serous carcinoma A. Asaturova1, L.V. Adamyan2, M.V. Sannikova3, N.M. Fayzullina1, G.N. Khabas3, L.S. Ezhova1 1 Pathology, Federal State Budget Institution “Research Center for Obstetrics, Gynecology and Perinatology” Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation, 2Gynecological Surgery, Federal State Budget Institution “Research Center for Obstetrics, Gynecology and Perinatology” Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation, 3 Innovative gynecological oncology, Federal State Budget Institution “Research Center for Obstetrics, Gynecology and Perinatology” Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation Background: Ovarian high-grade serous carcinoma (HGSC) is one of the most aggressive and widely spread gynecological tumors all over the world. We studied the incidence of secretory cell expansion (SCE) and secretory cells outgrowth (SCOUT) in the of the fallopian tube in patients with gynecological pathology, determined their immunophenotype and biological role in the early stages of ovarian of HGCS searching the early diagnostic test for HGSC. Methods: 287 patients with benign serous ovarian cystadenomas (n ¼ 75), borderline serous ovarian tumors (n ¼ 73), HGSC (n ¼ 69) and extraovarian pathology (n ¼ 70) were recruited, the fallopian tubes were investigated morphologically and immunohistochemically (p53, Ki-67, PAX2, bcl-2, beta-catenin, ALDH1) with semiquantative assessment (0 for negative, 1 – for weak, 2 – for moderate and 3 – for strong expression. Mann-Whitney and v2 tests was used for statistics. Results: Incidence of SCE (> 10 secretory cells in a row) and SCOUT (> 30 secretory cells in a row) increases with age in all groups. SCE were revealed 5.9-fold more frequent in patients with HGSC than in patients with extraovarian pathology (p < 0.01), while SCOUT were revealed 3.4-fold more frequent (p < 0.05). PAX2 expression in normal epithelium was 2.8, in SCE - 1.3, in SCOUT -1.2, in HGSC - 0.9. bcl-2 expression in the normal epithelium was 2.2, the SCE - 2.1, in SCOUT – 2.2, in HGSC – 0.6, beta-catenin ix98 | abstracts Bevacizumab in ovarian cancer: Experience in a tertiary hospital of northern Taiwan W-C. Chen, J-T. Qiu, T-C. Chang, C-H. Lai Gynecologic Oncology, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan Background: Bevacizumab (BEV) has been used for ovarian cancer (OC) for years in Taiwan, but the associated data and outcome is scanty and less. This retrospective study tracked back the patients with OC treated with BEV and analyzed the report. Methods: All 89 patients with OC had ever treated with BEV during 2009 to 2015 in Chang Gung Memorial Hospital of Linkou branch in Northern Taiwan. According to the means of administration, all the patient can be classified as 6 groups as followings: A-BEV plus chemotherapy (C/T) in initial platinum-resistant (PR) recurrent OC, BBEV plus C/T in initial platinum-sensitive (PS) recurrent OC, C-BEV alone in recurrent OC, D-BEV plus 1st adjuvant C/T, and E-BEV plus neoadjuvent C/T, F-Intraperitoneal (IP) BEV. Progression-free survival (PFS), overall survival (OS), hazard ratio (HR), overall response rate (ORR), and median BEV cycles were analyzed for group A to E. Clinical improvement of ascites was assessed for group F. Results: Between early use (only one line of prior C/T) and late use (multiple lines of prior C/T) in patients of group A and B, better PFS (8.27 VS. 3.67, p .037) was found in early use group. No significant differences were found between group A and B (PFS: 4.24 VS. 4.17 months, p .690; OS: 10.06 VS. 9.93 months, p .819; median BEV cycles: 4.63 VS. 5.0 p .992; ORR: 48.1% VS. 53.5%, p .425). Between response and non-response subgroup in patients of group A and B, better outcome is related with endometrioid type cell (HR ¼ 0.28, p .008), well ECOG performance status (HR ¼ 0.51, p .005), and patients without ascites (HR ¼ 0.67, p .004). Between group C with A plus B, BEV alone group has poorer PFS (1.02 VS. 4.19, p .04) and OS (1.42 VS. 9.99 p .001) than BEV plus C/T. In group F, good clinical benefit rate (85.6%) of ascites improvement was noted. Two cases had grade 5 gastrointestinal bleeding and venous/arterial thromboembolic events respectively after BEV used. Grade 3 neutropenia and thrombocytopenia were much more in our study. Conclusions: Early use of BEV to combine with chemotherapy had significant benefit of PFS in recurrent OC patients. BEV plus chemotherapy is better than BEV alone for recurrent OC. Besides, IP used BEV also has help for clinical ascites. Legal entity responsible for the study: Chang Gung Memorial Hospital GYN Oncology Department Funding: N/A Disclosure: All authors have declared no conflicts of interest. 315P Correlation between the expression of heat shock proteins and the prognosis of advanced ovarian serous adenocarcinoma J. Zuo Gynecologic Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China Background: Heat shock protein (HSP) family is overexpressed in many malignant tumors, which plays an important role in drug resistance and prognosis. The present study is aimed to screen the prognosis-related HSP expression in serous ovarian cancers and to evaluate the association between it’s expression and survival in ovarian serous adenocarcinoma (AOSC). Methods: HSPs were tested in ovarian cancer specimens by Western Blot in order to detect the candidate proteins whose expressed differently in platium-sensitive and resistent AOSC tumors. Paraffin-embedded tissues from 202 AOSC patients who underwent the primary debulking surgery from 2003 to 2013 were transferred to tissue microarray in which the cadidate HSPs were evaluated by Immunohistochemical analysis. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology Results: HSP90AB1 and TRAP1 were determined as the candidate proteins. In general, HSP90AB1 had high expression rate of 59.9% (121/202) and TRAP1 had low expression of 36.6% (74/202). There was no significant correlation between HSP90AB1 expression and clinicopathological factors while TRAP1 expression was correlated with platinumresistance and preoperative CA125 levels (P ¼ 0.05, 0.034) and weak correlation with other clinicopathological factors. Univariate analysis demonstrated that patients with high HSP90AB1 expression had poor prognosis with worse overallsurvival(OS), progression-free survival(PFS) and treatment-free interval(TFI) as compared to those with low expression (P ¼ 0.003,0.029,0.032, respectively). Patients with high TRAP1 expression had better prognosis in OS, PFS and TFI (P < 0.001, ¼ 0.03, ¼ 0.035, respectively) as compared to those with low expression. Multivariate analysis found that overall survival in patients with HSP90AB1 high expression was significantly shortened (P ¼ 0.044, HR1.573, 95% CI 1.013-2.443,) while patients with TRAP1 high express had better overall survival (P < 0.001, HR 0.427,95% CI 0.269-0.678). Conclusions: HSP90AB1, TRAP1 expression are strong prognostic factors in AOSC, which high HSP90AB1 expression level indicates poor prognosis and high TRAP1 expression level indicates good prognosis. Legal entity responsible for the study: Cancer Institute & Hospital, Chinese Academy of Medical Science and Peking Union Medical College Funding: China National Center for Biotechnology Development Disclosure: All authors have declared no conflicts of interest. 316P Disruption of DNA double strand break repair by VCP inhibition in ovarian and pancreatic cancer Y. Astuti1, H. Gabra2, H. Wasan2, E. Maginn1 Surgery & Cancer, Imperial College London - Hammersmith Hospital, London, UK, 2Cancer and Surgery, Imperial College London - Hammersmith Hospital, London, UK characteristics, disease characteristics, time to progression, overall survival and their fate. BMI was calculated using the formula weight (in kilograms) divided by height (in meters) squared and was graded according to World Health Organization (WHO) system. Results were collected, tabulated and statistically analyzed by an IBM compatible personal computer with SPSS statistical package version 20. Results: Within the studied group 3 patients (4.5%) were underweight, 11 (16.7%) had normal BMI, 17 (25.8%) were overweight, 13 (19.7%) had moderate obesity, 8 (12.1%) had severe obesity and 14 (21.2%) had very severe obesity. There were no significant associations regarding BMI and disease stage, pathology, initial tumor marker level, platinum sensitivity and overall survival. Conclusions: In epithelial ovarian cancer patients, high BMI had no significant relation with disease stage, and platinum sensitivity and did not adversely affect time to progression and overall survival. Legal entity responsible for the study: Menoufia University Funding: Menoufia University Disclosure: All authors have declared no conflicts of interest. 318P Antiproliferative effect of Moringaoleifera root extract on ovarian carcinoma: An in vitro study A. Ghosh1, R. Bhattacharya1, C. Pradhan2, K. Chaudhuri1, A. Mukhopadhyay1, C.K. Bose1 1 Molecular Biology, Netaji Subhas Chandra Bose Cancer Research Institute, Kolkata, India, 2Human genetics, Indian Institute of Chemical Biology, Kolkata, India 1 Background: Ovarian and pancreatic cancers are often characterized by defective DNA damage repair (DDR), which can be associated with resistance to DNA-damaging chemotherapy. Targeting the DDR network is thus a promising strategy to enhance chemosensitivity in these malignancies. We have previously performed siRNA screening to identify the potential of DDR regulators as treatments for these chemoresistant cancers. Several ubiquitin proteasome pathway regulators, including valosin-containing protein/p97 (VCP) were identified. Here we show the effect of VCP inhibition on apoptosis and DNA double strand break (DSB) repair in ovarian and pancreatic cancer cell lines. Methods: Inhibition of VCP was carried out using the pharmacological inhibitor NMS873, and MG-132 was used to inhibit proteasome activity. Apoptotic induction was determined by measuring caspase-3/7 activities and protein expression was assessed using western blotting. DSB foci were detected using immunofluorescence microscopy, and interaction between VCP and DDR proteins was assessed using proximity ligation assays. Results: Treatment with NMS-873 significantly induced apoptosis and sensitised resistant ovarian and pancreatic cancer cell lines to cisplatin. NMS-873 treatment also decreased the efficiency of non-homologous end joining and homologous recombination (HR) DSB repair pathways. Additionally, this inhibition reduced Rad51 foci formation during HR. This was shown to be the result of a reduction in Rad51 protein levels following treatment with NMS-873 and this was prevented by proteasome inhibition. Analysis of protein interactions suggests that VCP interacts with Rad51 in the nucleus. Conclusions: Overall, our data demonstrate the potential of VCP as a therapeutic target in ovarian and pancreatic cancers, and delineate a novel mechanism by which VCP regulates stability of Rad51 in these cancers. Legal entity responsible for the study: Imperial College London Funding: Ovarian Cancer Action Plum Unlimited Disclosure: All authors have declared no conflicts of interest. Background: Ovarian cancer is the deadliest of gynecologic cancers worldwide, ranking as the third most common cancer among women, In India. Hence there is an unmet need to find out its etiology as well as cure. Previous reports have established the role of extracts of Moringa oleifera, a native tree from India, in attenuating breast or pancreatic cancer but not on ovarian cancer. Our aim of the present study was to understand the role Moringa oliefera on ovarian cancer, as its putative FSHR antagonistic role was suggested before. Methods: To determine viability of ovarian cancer cells upon treatment with Moringa extract, the MTT assay was used, following standard protocol (1), with little modification. Briefly, OAW-42 (1 106 cells/ml) were cultured in a T-75 flask and transferred to a 96-well plate (1x104cells/well) and kept for one day at 37oC, then they were exposed to varying concentrations of Moringa root extract alone or in combination with sublethal toxicity dose of Paclitaxal or cisplatin, for 24 h. For both treated and control cells, Western blot analysis was performed using standard protocol to check its effect on apoptosis. To see the effect of Moringa root extract on cancer cell proliferation Clonogenic assay was carried out according to standard protocol (2). Results: The dose dependent analysison viabilityof OAW-42 cells by MTT assay showed 50% lethal toxicity (IC-50) of MRE (moringa root extract) to be 250lg/ml and even less (150mg/ml) in combinational treatment with cisplatin and Paclitaxal at a sublethal dose of their toxicity (250 mM and 30ng/ml respectively), without any apparent cytotoxicity on normal cells at the same dose. Our data showed MRE at its IC50 value (250mg/ml) had effect in case of cleaved caspase-9. However it did not show much effect on cleaved caspase-8. In clonogenic assay approximately 40% reduction of colony formation was observed in treated plate than the control plate, indicating the potential of MRE in attenuating the survival of ovarian cancer cells. Conclusions: We can conclude that MRE is a promising candidate for treatment of ovarian cancer, alone or in combination with traditional chemotherapeutic drugs like cisplatin and Paclitaxol at a sublethal dose of their toxicity. Legal entity responsible for the study: N/A Funding: Netaji Subhas Chandra Bose Cancer Research Institute Disclosure: All authors have declared no conflicts of interest. 319P 317P Effect of body mass index on survival in patients with epithelial ovarian cancer 1 1 2 S.F. Gohar , A. Abdel Ghany , S.S. Soliman Clinical oncology, Faculty of Medicine - Menoufia University, Shebin El Kom, Egypt, 2Public health and community medicine, Faculty of Medicine - Menoufia University, Shebin El Kom, Egypt 1 Background: Higher body mass index (BMI) is an independent and well-established prognostic factor for mortality for several hormone-related cancers, such as breast and endometrial cancer. As a hormone-dependent cancer, ovarian cancer, however, has been inked inconsistently to obesity. Approximately 12% of patients with ovarian cancer are obese. Methods: This retrospective study included 66 patients with epithelial ovarian cancer who came to oncology department Menoufia University from January 2011 to April 2014. Patient data were collected, from patients’ files including their epidemiological Volume 27 | Supplement 9 | December 2016 Choriocarcinoma: A 10 year tertiary care cancer hospital experience S. Yasmeen Medical Oncology, Shaukat Khanum Memorial Cancer Hospital and Reserch Centre (SKM), Lahore, Pakistan Background: Gestational chorio-carcinomas are highly malignant tumors of trophoblastic tissue occuring during or after pregnancy. Very little data is available in Pakistan. Methods: Patients diagnosed as choriocarcinoma managed at Shaukat Khanum Cancer hospital, Lahore, Pakistan from 2005 to 2015 were included. Data was recorded on age, risk scoring, pre and post-operative B-human chorionic gonadotropins (B-hCG) levels, treatment, type and number of chemotherapy cycles, type of surgery and overall survival (OS). OS by Kaplan Meier method was the interval between the date of diagnosis and last visit/death. doi:10.1093/annonc/mdw585 | ix99 abstracts Results: Thirty eight patients with choriocarcinoma with median age of 25 years were included. Using FIGO staging, stage 1 was identified in 7, II in 1, III in 14, IV in 8 and unknown in 8 patients respectively. Pre-treatment Beta-hCG ranged from 28 to 921000 ug/l. Twenty-seven patients (71.0%) had high risk category, 7 (18.4%) in medium risk and 4 (10.5%) had low risk. EMA-CO was the most common initial regimen (35 patients). Four patients, as non-responders to EMA-CO, were later on treated by EP-EMA protocol. Median number of chemotherapy cycles was 6. Mean time to normalization of Beta-hCG was 7.26 þ 2.24 weeks. Thirty three patients completed all chemotherapy cycles. Post treatment Beta-hCG levels normalized in all patients except four nonresponders to EMA-CO; however disease was not controlled in these patients. Thirty three patients achieved complete response. Five patients expired, while 3 were lost to follow up after treatment. Thirty out of 38 patients were alive at median follow up of 52 months. Median survival by Kaplan Meier method was yet not reached. Conclusions: Choriocarcinoma is a curable malignancy and chemotherapy can achieve high cure rates and inadvertent surgery should be avoided in all cases unless deemed necessary. Legal entity responsible for the study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Funding: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Disclosure: All authors have declared no conflicts of interest. 320P Adjuvant chemotherapy comprising a paclitaxel and carboplatin regimen or paclitaxel and ifosfamide regimen for uterine carcinosarcoma, a single institutional retrospective study Y. Ohtake1, T. Nishikawa1, H. Yoshida2, M. Ishikawa3, S. Ikeda3, T. Kato3, A. Shimomura1, T. Shimoi1, E. Noguchi1, K. Yonemori1, C. Shimizu1, M. Yunokawa1, K. Tamura1 1 Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan, 2Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan, 3Department of Gynecology, National Cancer Center Hospital, Tokyo, Japan Background: Uterine carcinosarcoma (UCS) is a rare form of cancer with poor prognosis. It is unclear whether adjuvant chemotherapy improves the prognosis in these patients. The aim of this retrospective study was to assess the efficacy of adjuvant chemotherapy after primary surgery for UCS. Methods: Data for patients who underwent comlete surgical resection of UCS between 2002 and 2015 were retrospectively analyzed. The patients were classified into three groups: those who did not receive adjuvant chemotherapy (the surgery only group), those who received paclitaxel and carboplatin (TC; carboplatin AUC6 þ paclitaxel 175mg/m2 q3w, 6 cycles; TC group), and those who received paclitaxel and ifosfamide (TI; ifosfamide 1.6g/m2 þ paclitaxel 175mg/m2 q3w, 8 cycles; TI group).We compared the recurrence-free survival (RFS) and overall survival (OS) among the three groups. Results: A total of 41 patients were identified, with 20 patients in the surgery only group, 7 patients in the TC group, and 14 patients in the IT group. The patient and tumor characteristics in the surgery only group, TC group, and TI group were as follows, respectively: (mean age) 63.5; 56.0; 62.0, (clinical stage I/II/II/IV) 10/0/8/2; 1/1/ 3/2; 11/1/6/2, (homologous/heterologous with sarcoma component) 11/9; 5/2; 11/3, and (endometrioid/serous/not determined in carcinoma component:) 11/2/7; 1/4/2; 6/7/1. No significant differences in these characteristics were observed between the three groups. Moreover, TC or TI group did not demonstrate significant defferrence in RFS (P ¼ 0.558, 0.410) and OS (P ¼ 0.844, 0.663) compared with the surgery only group. Conclusions: According to the findings of this study, adjuvant chemotherapy did not improve the RFS and OS in patients with UCS after complete surgical resection. However, the retrospective nature of the study and a small sample size warrant further studies for a definitive conclusion. Legal entity responsible for the study: Yohei Ohtake Funding: Japan Agency for MedicalResearch and Development Disclosure: All authors have declared no conflicts of interest. Annals of Oncology endometrial carcinoma, serous adenocarcinoma, clear cell carcinoma, and mucinous carcinoma. No studies assessing optimal surveillance after initial treatment for endometrial cancer have been performed. This study aimed to determine the association between cancer type and recurrence time as well as the effect of prognostic factors. Methods: Charts for patients with endometrial cancer who underwent surgery between January 2005 and December 2011 were retrospectively reviewed, and clinicopathological features and clinical courses were compared between patients with type 1 and type 2 disease. Cumulative incidence curves for recurrence were estimated, and the association between the time of relapse and cancer type was assessed by multivariate logistic regression. Results: Three hundred seventeen patients with type 1 disease and 106 patients with type 2 disease were evaluable. Advanced stage (stage III or IV) was more commonly found among patients with type 2 endometrial cancer (12% vs. 30.2%, p < 0.05). Progression-free survival was significantly worse in patients with type 2 disease, and it was also worse in patients with early stage disease. Type 2 diagnosis was an independent poor prognostic factor of poor progression-free survival and disease-specific survival by multivariate Cox regression analysis. The 2-year and 5-year recurrence rates in patients with type 1 disease were 3% and 8%, while the rates in patients with type 2 disease were 25% and 30%, respectively. Almost all patients with type 2 disease experienced recurrence within 2 years. Conclusions: Type 2 of endometrial cancer recurred earlier than type 1 disease. More careful surveillance after initial treatment is needed for patients with type 2 endometrial cancer, especially in the first 2 years. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 322P M.K. Kim Obstetrics and Gynecology, Samsung Changwon Hospital Sung Kyun Kwan University, Changwon, Republic of Korea Background: Lynch syndrome increase risk of mostly endometrial cancer and colorectal cancer. There is not much study about detecting algorithm among Korean population by gynecologic oncology surgeon. We undertook this study to investigate this. Methods: A retrospective review of endometrial cancer patients who was counseled about Lynch syndrome in Department of Obstetrics and gynecology, Samsung Changwon Hospital by single surgeon was done. Clinical information was extracted from the medical record including age, family and personal history of cancer, immunohistochemistry(IHC), microsatellite instability test(MSI), and gene sequencing results. Risk management and posttest education after result were offered about risk reducing options and cascade testing for affected individual Results: Total test was 16.There were two germline mutations (both MSH2) (c.23C>T (p.Thr8Met), c.187delG (p.Val63*).Both were negative for MSH2 IHC, But no patient matched criteria of Amsterdam. Four variation of unknown significance (VUS) was found (Three MSH2 and One MLH1).Among those all were abnormal in IHC and there was only one Amsterdam criteria matched patient. There were two unstable MSI patients, one was MSH2 germline mutation and the other was MSH2 VUS. Median age was 57(4176).Most cases were endometrioid type (11/16, 69%).Seventy five percent were stage I(12/16). Conclusions: We found two MSH2 germline mutation patients among this population. Gynecologic oncology surgeon can be adapted to develop the ability to assess and evaluate genetic risk among endometrial cancer. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 323P 321P Clinical course comparison between patients with type 1 and type 2 uterine endometrial cancers Y. Takehara1, M. Yunokawa1, S. Sasada1, E. Noguchi1, A. Shimomura1, T. Shimoi1, K. Yonemori1, C. Shimizu1, T. Kato2, K. Tamura1 1 Breast and Medical Oncology/Rare Cancer Center, National Cancer Center Hospital, Tokyo, Japan, 2Gynecology, National Cancer Center Hospital, Tokyo, Japan Background: Uterine endometrial cancer is classified into two groups: type 1, which includes grades 1 and 2 endometrial carcinoma; and type 2, which includes grade 3 ix100 | abstracts Rapid genetic screening experience among endometrial cancer about Lynch syndrome by surgeon The role of SUVmax in 18F-FDG PET/CT for assessing radiation therapy response for cervical cancer S.H. Lee1, K.C. Lee1, K. Sung1, E.Y. Choi1, J.B. Bae1, S.G. Kim2, H. Lee2 Radiation Oncology, Gachon University Gil Hospital, Incheon, Republic of Korea, 2Nuclear Medicine, Gachon University Gil Hospital, Incheon, Republic of Korea 1 Background: We assessed the relationship between primary tumor 18Ffluorodeoxyglucose (FDG) uptake expressed as the maximum standardized uptake value (SUVmax), primary tumor response, and survival in patients with cervical cancer on pretreatment and posttreatment positron emission tomography-computed tomography (PET-CT). Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology Methods: We conducted a retrospective review of 35 cervical cancer patients (stage I-II: n ¼ 19; stage III-IV: n ¼ 16) treated with radiation therapy with or without chemotherapy. All patients (median age, 58.5 years; range, 3781 years) had FDG PETCT scans performed before and after radiation therapy (pre- and post-RT). The SUVmax were recorded from PET-CT scans performed pre- and post-RT. The correlation between SUVmax and treatment response was evaluated and analyzed. Measurement of primary tumor volumes (pTV) for the treatment response evaluation was performed by the diagnostic radiologist using magnetic resonance imaging or abdominopelvic CT. Results: The median duration of follow-up was 42 months (range 5-72 months). The median SUVmax of cervical cancer pre- and post-RT were 10.1 (range: 4.3128.5) and 2.51 (range: 1.655.91), respectively. After treatment for cervical cancer, the reduction of SUVmax (median 7.4 (range: 0.0525.85)) was significant (p < 0.001). There was a significant correlation between post-RT SUVmax and post-RT pTV (r ¼ 0.470, p ¼ 0.004). There was also a significant correlation between SUVmax reduction rate and pTV reduction rate (r ¼ 0.447, p ¼ 0.007). A significant correlation was observed between post-RT SUVmax and the pTV reduction rate after RT (r¼-0.534, p ¼ 0.001). Conclusions: The SUVmax was significantly reduced after RT for cervical cancer. This study showed that the SUVmax after RT in patients with cervical cancer was significantly correlated with the primary tumor response. Legal entity responsible for the study: Gachon University Gil Medical Center Funding: Gachon University Gil Medical Center Disclosure: All authors have declared no conflicts of interest. 324P Radiation response assessment by hybrid positron emission tomography/magnetic resonance imaging for cervical cancer treatment B.A. Choo1, V. Koh1, J. Tang1, J. Low1, M.C. Stephenson2, D.L-H. Cheong2, E. Laurens2, J.J. Totman2, J.S-Y. Ng1, S. Roy2 1 Radiation Oncology, National University Cancer Institute, Singapore, 2A*STARNUS, Clinical Imaging Research Centre, Singapore Background: Treatment response after radiation therapy (RT) in locally advanced cervical cancer is commonly 2-3 months post-therapy. We aim to investigate the ability of hybrid PET-MRI to visualize tumour changes during the initial radiation phase, to optimise and personalised radiation dosage. Methods: All patients received four or five insertions of ring (Vienna) or ovoid (Utrecht) MRI compatible based brachytherapy in addition to five and half weeks of daily external RT. With the mandatory written informed consent, four multiparametric PET/MRI scans comprising of dynamic contrast-enhance imaging and diffusion weighted imaging were performed on each patient. The patients were examined first with 6mCi 18F-FDG scan at baseline. Prior to the first and third brachytherapy insertions, the patients were examined with the second and third 3mCi 18 F-FDG scans respectively. The last scan was performed 3 months post-treatment with 6mCi 18F-FDG as this will act as a prognosticator tool to assess whether a complete response has been achieved. Results: We report results of our pilot study. Aging between 46-55 years, all patients had histopathologically confirmed cervical cancer. On PET, metabolic target volume was 15.5-22.6 cm3 at baseline, with SUVmax 6.0-7.5 and SUVmean 4.3-5.4. MRI region of interest volume at baseline was 12.3-114.7 cm3. Good radiological treatment response was shown by all patients on both PET and MRI, with observations typically reflecting largest variation between the baseline and second scan (post external RT). A midtreatment increase in SUV occurred to one patient due to additional interstitial needle insertion during brachytherapy. At 3 months post-treatment, all patients attained complete radiological response. To date, there are no clinical locoregional recurrences. Conclusions: Significant treatment response to RT can be detected early using PET/ MRI, typically by end of external beam RT. The intention is to establish this finding through patient accrual. Personalized treatment concordant to tumour response may be developed. This will help to enhance cure rate and reduce potential side effects by giving a personalised radiation dose to the tumour rather than a standard protocolised dose. Clinical trial indentification: National University Hospital Singapore Institutional Review Board approved protocol number 2013/00052 Legal entity responsible for the study: National University Hospital Singapore Funding: National Cancer Institute Singapore Disclosure: All authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 325P Preliminary review of computed tomography (CT)-based image-guided brachytherapy (IGBT) in treatment of cervical cancers: The National Cancer Institute (NCI) experience N. Salimin, S. Mohammad, H.L. Goh, S.P. Tang, C.T. Chong, S. Mohd Salim, H.Z. Ahmad, N. Abdullah, M.Z. Muzzamer, A.N.A. Ahmad Sayuty, S.H. Abdul Rahman Radiotherapy & Oncology, National Cancer Institute (Institut Kanser Negara), Putrajaya, Malaysia Background: IGBT enables accurate planning of sufficient radiation doses to treat cervical cancers. NCI is the first facility in Ministry of Health of Malaysia to initiate this advanced technique. This review evaluates dose volume parameters of tumour & organs at risk (OAR) by CT-based treatment planning and clinical treatment outcomes Methods: Patients were treated with external beam radiotherapy (EBRT) to pelvis; 45Gy over 25 fractions with or without concurrent cisplatin chemotherapy, followed by 7Gy high dose rate (HDR) brachytherapy for 4 fractions with CT-based planning. All patients underwent pelvic Magnetic Resonance Imaging (MRI) prior to IGBT. We aimed to deliver minimum dose to 90% (D90) of high risk clinical target volume (HRCTV) of 75 Gy10, intermediate risk clinical target volume (IR-CTV) of 60Gy10 and dose volume constraint (D2cc) of 90Gy3 for urinary bladder & 70-75Gy3 for rectum & sigmoid colon. We evaluated toxicities clinically and radiological response via MRI. Results: From January 2014 to January 2016, 44 patients (median age 56-year-old) of FIGO stages IB-IVB were treated. Histology was squamous cell carcinoma in 33 patients (75%) and tumour size >5cm in 27 patients (61.4%). 30 patients (68.2%) received concurrent chemotherapy. Total prescribed mean dose for D90 was 86.9Gy for HRCTV, 67.7Gy for IR-CTV, D2cc 82.1Gy for urinary bladder, 69.1Gy for rectum and 60.9Gy for sigmoid colon. Median follow-up time was 6 months. 2 patients (4.5%) developed grade III vaginal stricture and 1 patient (2.3%) developed grade III cystitis. No grade IV toxicities observed. Out of 44 patients, 37 were evaluated with MRI. 7 patients (18.9%) achieved complete response and 29 patients (78.3%) had partial response by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Conclusions: We were able to achieve recommended dose to HR-CTV & IR-CTV and dose constraint for OAR. We recommend interstitial brachytherapy in larger tumours to improve dose received by tumour volume & minimize toxicity to OAR. Emphasis on follow-up to patients and standardised follow-up practice can improve reporting of clinical outcome. Legal entity responsible for the study: National Cancer Institute Funding: National Cancer Institute Disclosure: All authors have declared no conflicts of interest. 326P Biomarker discovery for early prediction of therapy resistance in cervical cancers B.A. Choo1, Z.W. Lee2, W. Zhao2, X. Wang2, J. Ng3, J. Low3, L.W. Deng2 Radiation Oncology, National University Cancer Institute, Singapore, 2 Biochemistry, National University of Singapore, Singapore, 3Obstetrics and Gynaecology, National University Cancer Institute, Singapore 1 Background: Cervical cancer is a common and deadly cancer among women worldwide. Resistance to radiation therapy poses a major obstacle in treatment. We hypothesize radiation resistant cells have different molecular signatures (biomarkers) from radiation sensitive cells. Hence, through the study of radiation resistant cell lines, we aim to evaluate the correlation between “stem-like” properties and cell line radiation resistance, to identify a panel of predictive biomarkers for radiation resistance and act as a prognostic tool. Methods: Parental HPV cells express high oncogenes- E6 and E7 and provide a selective growth advantage. Radiation resistant HeLa(HPV18) and SiHa(HPV16) was generated in-house. Characterization of the HPV cells was carried out with RT-PCR and soft agar assay to study the oncogene expression and transformation ability respectively. To study the “stem-like” property of the cells, they were subjected to “stem condition” and tested for CD44, CD24 surface markers. RNA isolation would be carried out on patient samples. Genes identified in cell line screen would be studied using RT-PCR. The cell line based genetic screen results would be validated against samples from both therapy sensitive and therapy resistant patients, Results: Positive correlation between the oncogene expression and radiation resistance was found. Microarray analysis of parental cells on functional clustering was done on 35 upregulated genes.11 genes were validated using RT-qPCR and most presented similar trend as microarray analysis, with CDH11 being the most promising. Under stem condition, the amount of stem-like cells (CD44high CD24low or CD49fpositive) increases across the parental, C1, C3 and C5 cells. This suggests a correlation between the amount of stem-like cells and radiation resistance. Levels of SLC2A3 and COL6A1 were also elevated across the parental cells grown in the adherent as well as stem condition. This suggests the potential to be predictive markers of radiation resistance. Conclusions: We have established and characterized radiation resistant cells through observation of the oncogene expression, transformation ability and stem-like property. Further validation with cervical biopsies samples is underway. doi:10.1093/annonc/mdw585 | ix101 abstracts Clinical trial indentification: National University Hospital Singapore Institutional Review Board approved protocol number 2015/00409 Legal entity responsible for the study: National University Hospital Singapore Funding: National Cancer Institute of Singapore and Terry Fox Foundation Disclosure: All authors have declared no conflicts of interest. 327P Nomogram prediction for overall survival of patients diagnosed with cervical cancer Annals of Oncology field, and time to relapse less than 6 months. No demonstrable prognostic factor was found in univariate analysis. Conclusions: Cisplatin plus irinotecan achieved a highest response rate and overall survival time without a significant difference when compare with other regimens. Further study with a larger population and prospective method is needed for the better conclusion. Clinical trial indentification: R136q/58_Exp November 10th, 2015 Legal entity responsible for the study: Phramongkutklao Hospital Funding: Phramongkutklao Hospital Disclosure: All authors have declared no conflicts of interest. S. Jagadeesan Radiation Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India 329P Background: Nomograms are predictive tools that are widely used for estimating cancer prognosis. The aim of this study was to develop a nomogram for the prediction of overall survival (OS) in patients diagnosed with cervical cancer. Methods: Cervical cancer databases of our institutie were analysed. Overall survival was defined as the clinical endpoint and OS probabilities were estimated using the KaplanMeier method. Based on the results of survival analyses and previous studies, relevant covariates were identified, a nomogram was constructed and validated using bootstrap cross-validation. Discrimination of the nomogram was quantified with the concordance probability. Results: In total, 42 consecutive patients with invasive cervical cancer, who had all nomogram variables available, were identified. Mean 5-year OS rates for patients with International Federation of Gynecologists and Obstetricians (FIGO) stage IA, IB, II, III, and IV were 99.0%, 88.6%, 65.8%, 58.7%, and 41.5%, respectively. two cancer-related deaths were observed during the follow-up period. FIGO stage, tumour size, tumour type histologic subtype, ph, parametrial involvement, endometrial invasion and organ involvement were selected as nomogram covariates. In our study, the total bad prognostic score mean value is 12. So, we derived more than 12 as high risk, more than 10-12 as intermediate risk and; less than 10 as low risk group. Based on predictor Lin‘s statistic concordance index value is 0.61. The normal value of C index is 6 1. In our study we had achieved perfect concordance index value which is suggestive of perfect normogram. Conclusions: Based on eight easily available parameters, a novel statistical model to predict OS of patients diagnosed with cervical cancer was constructed and validated. The model was implemented in a nomogram and provides accurate prediction of individual patients prognosis useful for patient counselling and deciding on follow-up strategies. Legal entity responsible for the study: Dr.V.Lokesh, Dr.Bindhu Joseph, Dr.Tanvir, Dr.Varatharaj,. Funding: Karnataka Disclosure: All authors have declared no conflicts of interest. 328P Survival outcomes in patients with stage IVB, persistent or recurrent adenocarcinoma of the cervix treated with combination chemotherapy T. Anantawat, K. Rittiluechai Gynecologic Oncology, Phramongkutklao Hospital, Bangkok, Thailand Accurancy of colposcopy at the Georgian National Screening Center T. Beruchashvili1, T. Alibegashvili1, T. Gogoladze1, R. Gvamichava2 Screening, National Screening Center, Tbilisi, Georgia, 2Screening, National Cancer Center of Georgia (NCCG), Tbilisi, Georgia 1 Background: Cervical cancer screening based on conventional cytology was launched in Georgia from 2008 by Georgian National Screening Centre (GNSC). Suspicious on High Grade SIL based on the cytology (ASC-H, HSIL) and colposcopy, or punch biopsy (CIN2þ) as well as persistence of CIN1 more than 2 years and/or CIN localization into cervical canal-are considered as indication for LEEP procedures. Methods: The retrospective analysis of 456 cases was performed. All woman underwent LEEP in GNSC at 2011-2014. The ages of woman and the results of PAP tests, colposcopy and following LEEP histopathology were transposed onto Excel spreadsheet for analysis. Results: The mean age of woman was 41 years (25-57). Distribution of referral cytology results was the following: ASCUS-14.5%, ASC-H-13.6%, LSIL-14.2%, HSIL-45.9% and NILM in 11.8% of all cases. Colposcopy diagnoses were LGSIL-93 (20.1%), HGSIL -298 (65%), neoplasia in the canal-38(8.3%) and normal colposcopic findings 30(6.6%)cases. The histological investigations of LEEP specimen showed: norm (without lesion)-36 (7.9), CIN1-144(31,6%), CIN2 -137(30%), CIN3 -125(27.4%) and microcarcinoma 14(3.1%) cases. Sensitivity, Specificity, PPV and NPV of Colposcopic diagnostics were calculated separately for LGSIL (CIN1) and HGSIL(CIN2þ) cases. For prediction of CIN1 accuracy of Colposcopy are: Se-61%, Sp-88%, PPV-77%, and NPV77%. In case of CIN2þ: Se:84%, Sp:70%, PPV-78% and NPV-76%. Overall results are: Se- 72%, Sp-86%, PPV-76% and NPV-83%. Conclusions: Colposcopy prediction for CIN2þis higher than for CIN1. Referral cytology has the influence on Colposcopy diagnosis. As the GNSC data outcomes reveals the similarities with results of other European studies they could be considered as The National parameters for Georgia. Legal entity responsible for the study: Georgian National Screening center Funding: Georgian National Screening center Disclosure: All authors have declared no conflicts of interest. 330P Skeletal muscle metastases from cervical cancer (two cases) S. Pervin1, D. Yeasmin1, F. Islam2, J. Ferdous3, A. Sikder4, A. Reza5 Gynae Oncology, National Institute of Cancer Research & Hospital, Dhaka, Bangladesh, 2Gynae Oncology, Railway General Hospital, Dhaka, Bangladesh, 3 Gynae Oncology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, 4Emergency, Upazilla Health Complex, Shariatpur, Bangladesh, 5 Radiotherapy, Delta Medical College and Hospital, Dhaka, Bangladesh 1 Background: Although the falling incidences of squamous cell carcinoma, the proportion of adenocarcinoma of uterine cervix increased with accounting for 15 to 24% of all cervical cancer cases. Controversial data about prognosis and survival of squamous cell carcinoma and adenocarcinoma of uterine cervix. The standard treatment of stage IVB, persistent or recurrent cervical carcinoma have not been established. A few prior studies had a majority of patient with adenocarcinoma. Various of chemotherapy regimens were used in these studies, and conclusions were still unclear. The main objective of this study was to evaluate an overall survival outcome of patients with stage IVB, persistent, or recurrent adenocarcinoma of uterine cervix in Phramongkutklao Hospital. A progression free survival, response rate, and prognostic factors were also calculated. Methods: A retrospective study was conducted. All patients with stage IVB, persistent, or recurrent disease who were treated between July 1993 and June 2013 were included. Patients’ baseline characteristics were collected. Overall survival and progression free survival were calculated by Kaplan-Meier survival analysis. Results: Forty patients were enrolled with a mean age of 51.4 years old. The chemotherapy regimens used in this study were cisplatin plus ifosfamide (CIf), cisplatin plus irinotecan (CIr), platinum-based chemotherapy plus paclitaxel (PP), and another 4 regimens. The median overall survivals of all 40 patients were 7.8 months. The median overall survivals were 6.7, 11.2, 5.5, and 9.3 months for CIf, CIr, PP and other regimens group, respectively. Most adverse effects were manageable. The most common adverse effect was hematologic toxicity. Many prognostic factors were evaluated in this study such as age > 60 years, hemoglobin level < 12 g/dl, relapse inside previous irradiation ix102 | abstracts Background: Cervical cancer is the second most common malignancy among Bangladeshi women. Metastases of cervical cancer to the skeletal muscle are very rare with a reported incidence <1%. Here we present two rare events of biceps muscle & gluteal muscle metastases as disseminated disease of cervical cancer. Methods: One 53 year-old and another 45 year-old patient, with known cases of cervical cancer (Post – treated) presented in the NICRH outpatient department on their regular follow up basis in May 2014 and June 2014 (one after 1 year and the other after 8 months of treatment) with one in biceps and the other in gluteal muscle metastases. Results: First patient had cancer cervix stage II(b) & second had stage III(b). The first patient was treated with EBRT & ICRT up to February 2014, and the second with CCRTþICRT up to January 2014. Both of them presented with pain & swelling. FNAC from the biceps muscle nodule revealed metastatic squamous cell carcinoma and wide local excision of gluteal mass histopathologically reported the same. Both of them were treated with local radiotherapy (15#) & palliative chemotherapy. Conclusions: Any painful soft tissue mass presenting in patients with known malignancy, has a high index of suspicion favoring metastases to the muscle rather than primary soft tissue sarcoma, as the latter is notably less painful. Volume 27 | Supplement 9 | December 2016 Annals of Oncology Legal entity responsible for the study: National Institute of Cancer Research & Hospital, Mohakhali, Dhaka, Bangladesh Funding: National Institute of Cancer Research & Hospital, Mohakhali, Dhaka, Bangladesh Disclosure: All authors have declared no conflicts of interest. 331P Synergistic effects of ferula gummosa and radiotherapy to induce cytotoxicity and apoptosis in the hela cell line A. Fani-Pakdel1, S.H. Forouzmand2, S.H. Mousavi3, V. Vazifedan2, M. Nourbakhsh1, S. Soleymanifard4, J. Chamani2 1 Cancer Research Center, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran, 2Department of Biochemistry and Biophysics, Islamic Azad University, Mashhad, Iran, 3Department of Pharmacology and Pharmacological, Mashhad University of Medical Sciences, Mashhad, Iran, 4Department of Medical Physics, Mashhad University of Medical Sciences, Mashhad, Iran abstracts (Apiaceae) is an extremely precious medicinal plant which naturally grows throughout the Mediterranean and Central Asia. The present study examined the cytotoxic effects on HeLa cells from the induction of apoptosis and radiation sensitivity by Ferula gummosa. Methods: HeLa cells were cultured in a RPMI1640 medium, incubated with different concentrations of Ferula gummosa (0-250 mg/ml), and afterwards exposed to 2 Gy crays. The cytotoxicity effect was determined by the MTT assay. Via flow cytometry, apoptotic cells were quantified by apropidium iodide (PI) staining of DNA fragmentation. Results: Ferula gummosa decreased cell viability in the HeLa cell line in a concentration- and time - dependent manner. Ferula gummosa compared to the control induced a sub-G1 peak in the flow cytometry histogram of treated cells thus indicating that apoptotic cell death is involved in Ferula gummosa-induced toxicity. It was also shown it can sensitize cells to radiation-induced toxicity and apoptosis. Conclusions: The concurrent use of Ferula gummosa and radiation increases radiation sensitivity and cell death. Therefore, Ferula gummosa can be considered as a potential agent and radiosensitizer in the medical treatment of cancer. Legal entity responsible for the study: N/A Funding: Mashhad University of Medical Sciences Disclosure: All authors have declared no conflicts of interest. Background: Cervical cancer is the second most common type of cancer among women worldwide, for which radiotherapy is a standard treatment. Ferula gummosa Boiss Volume 27 | Supplement 9 | December 2016 doi:10.1093/annonc/mdw585 | ix103 Annals of Oncology 27 (Supplement 9): ix104–ix111, 2016 doi:10.1093/annonc/mdw586 Haematological malignancies 332O Co-expression of PD-L1 and p-AKT is associated with poor prognosis in diffuse large B-cell lymphoma via PD-1/PD-L1 axis activating intracellular AKT/mTOR pathway in tumor cells abstracts H. Zhang1, X. Wang1, L. Dong1, H. Lv1, W. Li1, Z. Song1, L. Li1, S. Zhou1, L. Qiu1, Z. Qian1, X. Liu1, L. Feng1, B. Meng2, K. Fu3, X. Wang4, Q. Pan-Hammarström5, P. Wang6 1 Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China, 2Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China, 3Department of Pathology and Microbiology and Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA, 4Department of Cellular Biology, Tianjin Medical University, Tianjin, China, 5Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden, 6Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China Background: Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) engagement usually leads to diminished antitumor T-cell responses, which mediates the immune escape of tumor cells. However, little is known whether PD-1/PD-L1 could directly activates intracellular oncogenic signaling pathways in tumor cells. The purpose of this study is to investigate whether intracellular AKT/mTOR signaling could be directly activated by PD-1/PD-L1 during the malignant progression in diffuse large Bcell lymphoma (DLBCL). Methods: The immunohistochemistry (IHC) was used to detect expression of PD-L1 and p-AKT. Total PD-L1 proteins of DLBCL cells was determined by western blot. The membrane PD-L1 (mPD-L1) proteins of DLBCL cells was determined by flow cytometry. The survival analysis was performed using Kaplan-Meier method. Results: Detection of the expression of PD-L1 and p-AKT by immunohistochemistry (IHC) showed that both proteins were overexpressed in 54% and 48% DLBCL cases, respectively. Spearman test showed that PD-L1 expression was correlated with p-AKT expression (R ¼ 0.244, v2¼5.962; P ¼ 0.017) and the expression of PD-L1 and p-AKT were also correlated with clinic-pathological characteristics. In addition, survival analysis showed that DLBCL patients who co-expressed PD-L1 and p-AKT had significantly poorer outcome than patients with single positive or both negative expression (P < 0.05). In vitro, total PD-L1 and membrane PD-L1 (mPD-L1) proteins were overexpressed in five DLBCL cell lines by western blot and flow cytometry. We observed that AKT/mTOR pathway was activated in DLBCL cells after stimulated with human recombination PD-1/Fc. Conclusions: Our results suggested that the combination of PD-1/PD-L1 antibodies and AKT/mTOR inhibitor might be a promising and novel therapeutic approach for DLBCL in the future. Clinical trial indentification: ChiCTR-ONC-12002385 Legal entity responsible for the study: N/A Funding: Natural Science Foundation of China (81402945) Disclosure: All authors have declared no conflicts of interest. 333O Post-transplantation positron emission tomography scan is the main predictor of autologous stem cell transplantation outcome in diffuse large B cell lymphoma Z. Ying1, X. Wang2, Y. Zhang2, Y. Song1, W. Zheng1, X. Wang1, Y. Xie1, N. Lin1, M. Tu1, C. Zhang1, L. Ping1, W. Liu1, L. Deng1, J. Zhu1 1 Lymphoma, Peking University Cancer Hospital-Beijing Cancer Hospital, Beijing, China, 2Nuclear Medicine, Peking University Cancer Hospital-Beijing Cancer Hospital, Beijing, China Methods: Between Nov 2010 and Dec 2014, 65 patients with diffuse large B cell lymphoma were treated with HDC-ASCT at Peking University Cancer Hospital. 48 patients underwent PET imaging either before or after ASCT. Deauville criteria (5-point scale) was used to define negative (score 1,2 or 3) or positive (score 4 or 5) PET. The impact of pre- or post-ASCT PET on predicting prognosis were retrospectively analyzed. Results: Median age was 43. The median follow-up time was 30.5 months. In a univariate analysis, negative pre- and post-ASCT PET was associated with better progression-free survival (PFS) and overall survival (OS) than positive pre- and postASCT PET (pre-ASCT PET, p ¼ 0.007, p ¼ 0.011; post-ASCT PET, p ¼ 0.00, p ¼ 0.00). Patients were also classified into four groups according to PET results before and after ASCT: those who were negative before and after (-/-; n ¼ 26), positive before and negative after (þ/-; n ¼ 6), positive before and after (þ/-; n ¼ 8), negative before and positive after (-/þ, n ¼ 2). PFS and OS were significantly better for the -/- and þ/groups as compared with other groups (p ¼ 0.00, p ¼ 0.00). More importantly, there was no difference in terms of PFS and OS between the -/- group compared with þ/group. In the multivariate analysis, post-ASCT was identified as the only independent prognostic factor (PFS, p ¼ 0.001; OS, p ¼ 0.007). Conclusions: Our study demonstrated post-ASCT PET is the main prognostic factor in patients with DLBCL. Legal entity responsible for the study: Peking University Cancer Hospital IRB Funding: Peking University Cancer Hospital Disclosure: All authors have declared no conflicts of interest. 334O Additional chromosomal abnormalities in chronic myeloid leukemia: Lest we forget D. Madhav Medical Oncology, Nizam’s Institute of Medical Sciences, Hyderabad, India Background: Clonal cytogenetic evolution with additional cytogenetic aberrations (ACAs) in chronic myeloid leukemia (CML) are associated with adverse prognosis and decreased response to tyrosine kinase inhibitor therapy (TKI). The presence of ACAs at the time of diagnosis is now considered a criteria for accelerated phase. However, the differential prognostic impact of individual ACAs is unknown, and a formal classification system incorporating this information is lacking. Methods: In a retrospective analysis, we included data from 1,367 patients with CML treated with frontline Imatinib mesylate at a single institution between 2008 and 2014. The aim of the study was to stratify risk based on assumed prognostic impact of individual ACAs and determine their impact on survival endpoints. Results: ACAs were present in 92 of 1,367 patients (6.7%) at the time of diagnosis or progression. The common ACAs were trisomy 8 in 32 (2.3%) patients, additional Ph in 17(1.2%) patients, increased ploidy in 11(0.8%) patients, trisomy 19 and monosomy 7 in 9(0.6%) patients each, lack of Y chromosome and hypoploidy in 5(0.3%) patients each and 29 minor route (all other) ACAs. Variant Ph chromosome seen in 9(0.6%) patients was not considered an ACA. Survival outcomes were analysed based on stratification into group 1 including those without ACAs, group 2 including trisomy 8, -Y, an additional Ph chromosome, trisomy 19 and increased ploidy, group 3 including -7, i(17)(q10), 3q rearrangements, presence of 2 or more ACAs and hypoploidy, and group 4 with minor route ACAs. The overall survival was significantly better in group 1 in comparison with group 2, group 4 and group 3 respectively (Log-rank Mantel-Cox X2¼7.96, p ¼ 0.04). Conclusions: In an era where molecular monitoring takes precedence over all others in CML, cytogenetic monitoring is mandatory and must not be overlooked. A risk stratification system based on prognostic relevance of individual ACAs may be a useful guide to prognosticate and guide treatment of CML at diagnosis and clonal evolution, instead of the overtly simplified categorization of ACAs as major and minor route abnormalities. Legal entity responsible for the study: Nizam’s Institute of Medical Sciences Ethics Committee Funding: Nizam’s Institute of Medical Sciences Disclosure: All authors have declared no conflicts of interest. Background: The predictive value of 18F-FDG PET in patients with diffuse large B cell lymphoma (DLBCL) who are receiving high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT) remains a matter of debate. This study evaluated the role of 18F-FDG PET scan in patients with DLBCL before and after ASCT. C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts Annals of Oncology 335O Imatinib trough levels: A potential biomarker to predict cytogenetic and molecular response in newly diagnosed patients with chronic myeloid leukemia compared to those who did not receive radiation, with a survival rate of 75.5% and 86.1% respectively. Table: 336O H. Natarajan1, L. Kumar2, S. Bakhshi2, A. Sharma2, T. Velpandian1, A. Gogia2, Y.K. Gupta1 1 Clinical Pharmacology, All India Institute of Medical Sciences, New Delhi, India, 2 Medical Oncology, All India Institute of Medical Sciences, New Delhi, India Background: A good pharmacokinetic/pharmacodynamic correlation between imatinib exposure and therapeutic outcome has been reported. However, therapeutic drug monitoring (TDM) of imatinib in patients with Chronic Myeloid Leukemia (CML) is an ongoing debate. We studied the influence of imatinib trough levels on cytogenetic and molecular response in patients with CML. Methods: Newly diagnosed patients with chronic-phase CML, started on Imatinib therapy, were enrolled and followed-up prospectively for 24 months. Plasma trough levels of imatinib were measured using LC-MS/MS. Cytogenetic response was assessed by conventional bone-marrow cytogenetics. Molecular response was assessed by qRTPCR using international scale. Multivariate analysis was done to find the influence of various covariates on imatinib response. Results: A total of 206 newly diagnosed patients with CML were enrolled in this study. The mean age at diagnosis was 35.2614 years. Marked inter-individual variability was seen in imatinib trough levels (Coefficient of variation¼ 69%). Mean imatinib trough level was 190161305 ng/mL. Trough levels were significantly higher in patients who attained complete cytogenetic response than those who didn’t (2213.961101 vs. 1648.661403.4 ng/mL; P < 0.001). Patients with major molecular response (MMR) had higher trough levels than those without MMR (2333.461112 vs. 1643.461383.9 ng/mL; P ¼ 0.001). Patients with trough levels 1002 ng/mL were at a high risk for failure of imatinib therapy [RR ¼ 1.926; 95%CI (1.562, 2.374); P < 0.001]. Trough levels of imatinib emerged as an independent predictor of cytogenetic [adjusted OR: 10.488; 95%CI (4.136, 26.594); P < 0.001] and molecular response [adjusted OR: 14.407; 95%CI (3.414, 60.791); P < 0.001] in multivariate analysis. No significant correlation of trough levels with imatinib induced hematological toxicity was seen. Conclusions: Trough levels of imatinib significantly influence the cytogenetic and molecular response in patients with CML and might emerge as a potential biomarker to predict therapeutic response. TDM is recommended for individualizing the dosage of imatinib, especially in patients with suboptimal response. Legal entity responsible for the study: All India Institute of Medical Sciences, New Delhi, India Funding: All India Institute of Medical Sciences, New Delhi, India Disclosure: All authors have declared no conflicts of interest. 336O Survival patterns of acute lymphoblastic leukemia among adolescents and children in the USA I.O. Fadhlullah1, N.M. Elameen1, G.G. El Sehrawy2 Faculty of Medicine, Suez Canal University, Ismailia, Egypt, 2Rheumatology, Suez Canal University Teaching Hospital, Ismailia, Egypt 1 Background: Acute lymphoblastic leukemia (ALL) is a malignant disease in which normal hematopoietic cells of the bone marrow are replaced by the proliferating lymphoid precursors. ALL is considered the most common type of cancer in children worldwide. This study aims to assess different prognostic factors affecting 5-year survival rates of patients diagnosed with ALL in the SEER database. Methods: Patients’ data were obtained from SEER database. We selected cases by sex, race, age at diagnosis (from 2 to 19 years), immunophenotype, and utilization of radiation. We used Kaplan-Meier method to analyze relative 5-year survival rates of 8965 patients diagnosed with ALL between 1988 and 2007. Results: Out of 8965 patients diagnosed with ALL, who met our selection criteria, 57.5% were males, 82.9% were white, and 70.2% were children (aged between 2 to 9 years). A significant difference in relative 5-year survival rate was observed (p value < 0.001) in females which was 87% compared to males which was 83%. There was significant difference in relative 5-year survival rate (p value < 0.001) for white patients which was 85.2% compared to other races. Children showed a 5-year survival rate of 90.4% compared to adolescents’ survival rate which was 71.2%, (p value <0.001). B cell showed a survival rate of 85.7% compared to T cell survival of 76%, (p value <0.001). T cell showed a survival rate of 80.5% with radiation, while the survival rate decreased to 73.1% without radiation (p value 0.014). A significant difference in relative overall 5year survival rate (p value <0.001) was observed in patients treated with radiation Volume 27 | Supplement 9 | December 2016 Relative 5-year survival rate Variable Sex Race Age at Diagnosis Immunophenotype Radiation Male Female White Black Children Adolescents T-cell B-cell; Pre-B; B-Precursor Yes No Survival p 83% 87% 85.2% 79.4% 90.4% 71.2% 76% 85.7% <0.001 <0.001 <0.001 <0.001 75.5% 86.1% <0.001 Conclusions: Female patients, white races, children, patients with B cell immunophenotype, or those who did not receive radiation have shown better relative 5year survival rates. The relative 5-year survival rate of T cell immunophenotype improved with radiation. Legal entity responsible for the study: Inas Omar Fadhlullah Funding: Inas Omar Fadhlullah Disclosure: All authors have declared no conflicts of interest. 337O The changes in the treatment of elderly AML patients in Korea: A single center experience H. Ryu, I.C. Song, Y.S. Choi, S.W. Baek, J.Y. Moon, H.J. Lee, H.J. Yun, S. Kim, D.Y. Jo Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea Background: Decitabine have been used widely in the elderly AML patients, since the National Health Insurance system started to cover it in the November 2013 in Korea. This study was conducted to review the changes of the treatment pattern and draw the better treatment strategies. Methods: This study enrolled patients who were newly diagnosed with AML aged 65 years between 2010 and 2015 at Chungnam National University Hospital. The primary end point was overall survival, and the secondary end points were complete response (CR) rate, 1-year survival rate, and early mortality (death within 2 months). Results: In total, 42 patients were diagnosed with AML from Jan. 2011 to Oct. 2013 and 26 patients from Nov. 2013 to Dec. 2015. After the insurance of decitabine, the patients were treated with any kind of chemotherapy more frequently than before (84.6% v 54.8%, respectively, p < 0.001). Patients who were treated by induction chemotherapy (IC) had slightly longer survival than patients who were treated by decitabine (median OS; 10.0 (95% CI, 7.0-2.9) v 7.5 (95% CI, 3.8-11.2) months, respectively, p ¼ 0.315). Patient who had good performance status had significantly longer survival than those who had poor status (median OS; 11.5 (95% CI, 7.2-15.8) months in ECOG PS 0-1 v 4.3 (95% CI, 3.0-5.5) months in ECOG PS 2 v 1.5 (95% CI, 0.0-3.8) months in ECOG PS 3-4, p < 0.001). IC group had more patients with good performance than deciatbine group (ECOG PS 0-1; 86.2% v 37.5%, respectively, p < 0.001). The patient with WBC counts 30,000/uL had significantly poorer OS than those with WBC counts <30,000/uL in decitabine group (median OS; 2.4 (95% CI, 0.0-5.9) v 13.0 (95% CI, 5.3-20.7) months, respectively, p ¼ 0.02). In patients with age 70 years and WBC counts <30,000/uL, IC group and decitabine group had similar OS (median OS; 8.0 (95% CI, 3.2-12.8) v 7.0 (95% CI, 0.0-16.2) months, respectively, p ¼ 0.374). The CR rate was 62.1% with IC versus 25.0% with decitabine (p ¼ 0.017). But, the 1-year survival rate and early mortality rate were similar between IC and decitabine group (58.6% v 75.0%, p ¼ 0.272; 6.9% v 12.5%, respectively, p ¼ 0.527). Conclusions: These results indicate that decitabine is a reasonable treatment option in patients with age 70 years and WBC counts <30,000/uL. Legal entity responsible for the study: Chungnam National University Hospital IRB Funding: Chungnam National University Hospital Disclosure: All authors have declared no conflicts of interest. doi:10.1093/annonc/mdw586 | ix105 abstracts 338P Association of kynurenine, tryptophan and key enzymes involved in kynurenine pathway of tryptophan catabolism with Imatinib duration in patients with chronic myeloid leukemia D. Mohania1, Y. Shokeen2, M. Jauhri2, S. Aggarwal2 Research, Sir Ganga Ram Hospital, Delhi, India, 2Medical Oncology, Sir Ganga Ram Hospital, Delhi, India 1 Background: The kynurenine pathway could be a strong candidate for the missing link of immunosuppressive microenvironment in CML which has been demonstrated in a number of malignancies but not yet in CML patients. Methods: Patients were classified into three groups (responders, resistant and treatment naı̈ve) depending on their response to Imatinib (IM) therapy. The concentrations of the Trp and Kyn were measured by ELISA in the sera of 29 patients with CML and 19 healthy controls. We also investigated the expression of various key enzymes involved in kynurenine pathway for the first time in CML patients. Results: Trp concentrations were significantly lower in patients with CML (treatment responders, resistant and naı̈ve) than in healthy controls (p < 0.001), while Kyn concentrations were significantly higher in healthy controls compared with the CML patients (p < 0.001). Out of the 12 key enzymes (IDO-1, IDO-2, TDO-2, AFMID, KYNU, KAT-I, KAT-II, KAT-III, KMO, 3-HAAO, ACMSD, QPRT) analyzed in patients with CML, only kynurenine aminotransferase-III (KAT-III) showed a significantly (p¼.015) higher expression in resistant and treatment naı̈ve CML patients when compared to responders. Treatment resistant CML patients showed a positive correlation with the duration of Imatinib (months) intake along with the expression levels of Indoleamine 2, 3-dioxygenase-2 (r ¼ 0.864, p ¼ 0.041). Kyn concentrations and Kyn/Trp ratio showed a positive correlation in responders with the duration of Imatinib (months) intake. Furthermore, Trp concentrations also showed a positive correlation with the duration of Imatinib intake (months) in treatment resistant CML patients. Conclusions: The present study gives an important evidence for the first time about the association of key enzymes involved in tryptophan catabolism with Imatinib duration in treatment responsive, resistant and treatment naı̈ve CML patients. The prognostic power and relevance of this novel information remains to be elucidated in further larger studies. Legal entity responsible for the study: Sir Ganga Ram Hospital, New Delhi, India Funding: Department of Research, Sir Ganga Ram Hospital, New Delhi, India Disclosure: All authors have declared no conflicts of interest. 339P Annals of Oncology TKIs therapy. The TKIs supply via GIPAP and NOAT improves the outcomes in CML pts, leading to the recovery and restoration of the ability to work. Clinical trial indentification: The Council approval number 8/6 Legal entity responsible for the study: State University of Medicine and Pharmacy, Institute of Oncology Funding: Axios International, Novartis Disclosure: All authors have declared no conflicts of interest. 340P R.R. Ganta1, S. Nasaka1, V. Linga1, S. Gundeti2, L.S. Maddali2, R. Digumarti3 Medical Oncology, Nizam’s Institute of Medical Sciences, Hyderabad, India, 2 Dept. of Medical Oncology, Nizam’s Institute of Medical Sciences, Hyderabad, India, 3Medical Oncology, Homi Bhabha Cancer Hospital & Research Center, Visakhapatnam, India 1 Background: High body mass index (BMI) has been identified as a poor prognostic factor for several malignancies including chronic myeloid leukemia (CML). To date, studies correlating baseline BMI and response to imatinib in CML are limited. We analyzed our data to study the BMI and its relation with the response rates in adolescent and young adult (AYA) CML CP patients on Imatinib. Methods: Hospital records of AYA CML CP patients (age 15-29 years) from 2008 to 2012, were analyzed retrospectively for BMI and attainment of cytogenetic and molecular response. They were grouped as low BMI (25) and high BMI (>25). Results: A total of 56 patients were included in this study, with the median age of 21 years and male preponderance (M:F- 1.3:1). Majority (67%) of them had low BMI and rest had high BMI. Complete hematological response rate at 3 months was 100% in both low and high BMI groups. Complete cytogenetic response rate at 12 months was 65% and 89% in low and high BMI groups respectively. Major molecular response rate at 18 months was 78% and 89% in low and high BMI groups respectively. Four year EFS was 100% in both low and high BMI groups. Table: 340P Chronic myeloid leukemia: diagnosis, management and treatment options in Moldova CHR at 3 month CCyR at 12 month MMR at 18 month EFS at 4 years V. Musteata Oncology, Hematology and Radiotherapy Department, State University of Medicine and Pharmacy “N. Testemitanu”, Institute of Oncology, Chisinau, Moldova Background: We consider the management of chronic myeloid leukemia (CML) challenging due to untimely diagnosis and mostly reserved prognosis. Methods: The cohort study enrolled 125 CML patients (pts), followed up at the Institute of Oncology. The male/female ratio was 1.4:1. The age ranged between 19 – 81 years. Chronic phase was diagnosed in 113 (90.462.32%) cases, accelerated and acute phases – in 12 (9.662.02%). Ph-positive marrow cells exceeded 75% in 72.7% of pts. 81 (64.8%) pts were approved for GIPAP, 4 (4.0%) – for NOAT program. Imatinib was used as a front-line therapy in 19 (22.1%) cases, and in 67 (77.9%) cases of the relapse or resistance to non-TKIs therapy. Of 21 (24.4%) imatinib-resistant pts, 10 (47.6%) received dasatinib therapy. Results: The CML prevalence increased (2004 – 2,11%jjj, 2010 – 3,40%jjj, 2014 – 4,16%jjj). The mostly affected age group was 40 – 49 years (27.464.89%). 59.664.99% of pts were exposed to insolation during their activities (correlation coefficient 0.479). Complete hematologic response (CHR) rate was 85.1% under TKIs therapy and outruned (p < 0.05) the remission rate obtained with non-TKIs therapy. 9 (42.9%) imatinib-resistant pts responded completely to dasatinib. All dasatinib-treated pts achieved CHR after the front-line non-TKIs therapy. The complete cytogenetic response rate was 26.3% after TKIs treatment. The inclusion in GIPAP and NOAT programs improved (p < 0.01) the ECOG-WHO score up to 0–1 in 90.5% of pts (P6ES% ¼ 0.2560.06), as compared to non-TKIs therapy. The 3-year survival in imatinib-treated pts (66.0%) exceeded (p < 0.05) that one achieved after non-TKIs therapy (44.5%). The median survival proved to be higher (p < 0.05) in the age group of 40–49 years (61.6564.81 months), as compared with the groups of 20–29 (43.1362.80 months) and over 70 (43.1463.92 months) years. The 3-year survival was superior (p < 0.05) in females (66%) than in males (51%). Conclusions: CML occurs commonly in a workable male population. The insolation may be suggested as a favoring factor in pathogenesis of CML. The pts managed with TKIs achieved much higher CHR and survival, as compared to pts treated with non- ix106 | abstracts Cytogenetic and molecular response rates in AYA CML CP patients on imatinib based on the baseline BMI Low BMI (25) n ¼ 38 (67%) High BMI (>25) n ¼ 18 (33%) Fishers test p valve 38 (100%) 25 (65%) 30 (78%) 38 (100%) 18 (100%) 16 (89%) 16 (89%) 18 (100%) 1 0.1 0.47 1 Conclusions: High BMI CML patients on imatinib showed numerically better response than low BMI patients but statistically not significant. The reasons for these results are not known at present and need to be tested in a prospective study. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 341P The role and significance of myeloid-derived suppressor cells-like blasts in immune-tolerance of acute myeloid leukemia S.Y. Hyun1, J-W. Cheong2 Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea, 2Internal Medicine, Yonsei University College of Medicine Department of Internal Medicine, Seoul, Republic of Korea 1 Background: Myeloid-derived suppressor cells (MDSCs) have an ability to suppress Tcell function and have been known to facilitate tumor growth. We elucidated the role of leukemic subpopulation which resembles MDSC in acute myeloid leukemia. Methods: CD11bþCD33þHLA-DR- blast (MDSC like blast) were isolated using flowcytometry from bone marrow mononuclear cells of each patients. CD14, CD15, Arg1 and iNOS expression were checked by flow-cytometry. To confirm the immunosuppressive function, co-culture with normal CD8þ T cell with/without PHA was conducted. A clinical impact was reviewed in 63 patients with retrospective chart review. Results: MDSCs like blast can be divided into two subtypes, monocytic subgroup expressing CD14 and granulocytic subgroup expressing CD15, and CD14 expression Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology was more frequent than CD15 (67.5% vs. 39.3%). MDSC-like blasts showed higher expression of Arg1 (77.1% vs. 38.5%, P < 0.001) and iNOS (33.0% vs. 1.1%, P < 0.0001) compared to non-MDSC-like blasts. CD8þ T cell proliferation induced by PHA was significantly suppressed when co-cultured with MDSC-like blasts compared to without them. Patients with a higher fraction of MDSC-like blasts showed a significantly shorter overall survival (331642 vs. 7586114 days, P ¼ 0.027) and also tended to have shorter leukemia-free survival (341647 vs. 7306116 days, P ¼ 0.062). Multivariate analysis showed that higher fraction of MDSC-like blasts (Hazard ratio 2.966, 95% CI 1.0868.095, P ¼ 0.034), old age (P ¼ 0.001), adverse cytogenetics (P ¼ 0.013), and FAB classification P ¼ 0.035) were poor prognostic factors for short overall survival. Conclusions: CD33þHLA-DR- MDSC-like blasts subgroup existed in myeloid blasts and suppressed T cell immunity. It also showed adverse prognostic effect on survival. MDSC-like blasts might play a certain role in immune-tolerance in leukemia. Clinical trial indentification: Institutional Review Board of Severance (Clinical Trial Number 4-2010-0669) Legal entity responsible for the study: Institutional Review Board of Severance Hospital(Clinical Trial Number 4-2010-0669 Funding: This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning(2016-52-0077) Disclosure: All authors have declared no conflicts of interest. 342P Social impact of pediatric acute myeloid leukaemia (AML) is biggest challenge in eastern India – A demographic, clinical and psychological study good risk AML can range from 60% to 80% depending on the series . There is heterogeneity in the outcomes. Later on, it was realized that molecular markers including NPM1 and FLT3 play an important role in modifying the outcome. Although we have surplus of data on the outcome of good risk AML from the west, there is paucity of data from Indian subcontinent. Here we present the outcomes of good risk AML treated in our tertiary care cancer centre. Methods: all patients with good risk AML betweeen 17 to 65 yrs were analysed Good risk AML was defined as presence of t(8;21), inv 16, t(16;16). All our patient are treated with standard 3 þ 7 induction regimen that comprises of daunorubicin 60mg/m2 days 1-3 and cytarabine 100mg/m2 over 24 hours on days 1-7. Consolidation was given with high dose cytarabine, doses ranging from 9 to 12gm/m2 in six divided doses on days 1, 3 and 5. Results: total 87 patients were analysed. Males comprised of 49 patients . Baseline t(8;21) positive in 94% and inv 16 present in 6% cases. Morphological complete remission was documented in 90% of patients. A total of 38 patients were evaluated from cytogenetic status after induction, of which 24 patients achieved a complete cytogenetic remission (63.3%). There were a total of 11 (12.5%) deaths during induction, all of which were due to febrile neutropenia.A total of 51 patients (59.34%) were alive till the time of analysis.The median follow period was 29. The 3 yrs relapse free survival was 72.1% and 3 yr overall survival was 56.7%. Conclusions: Our study shows that the survival of good risk AML is not always as expected. The heterogeneity was probably due to differences in the molecular characteristics, with both known and unknown markers till date. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. M. Sen, A. Datta, A. Mukhopadhyay Molecular Biology, Netaji Subhas Chandra Bose Cancer Research Institute, Kolkata, India Background: Pediatric Acute Myeloid Leukemia (AML) is becoming an emerging health challenge in eastern India thus affecting not only physical growth of children but also their mental well being. An observational study was conducted in a tertiary cancer centre of Eastern India to find out the association between clinical and psychological parameters of pediatric AML patients. However, a comparison was also drawn with healthy children of the same family. Methods: During May 2014 - July 2016, total 87 pediatric AML patients (53 male and 34 female) aged between 4-15 years attended OPD of Netaji Subhas Chandra Bose Cancer Research Institute, were studied for physical and mental status. Age and sex matched 43 healthy children (age range: 4- 15 years) from these affected families were also included as control group. Demographic factors (age, sex etc.) and clinical parameters (CBC, Electrolyte Analysis, RFT, and LFT etc.) were collected from hospital records. Behavior pattern was assessed by using Child Behavior Checklist from parents. We have compared those factors according to treatment plan. Finally, clinical parameters and behavioral pattern were compared between patients and healthy group. Results: The overall survival in 2 year was 70.2% in patients aged 15 years (with mean age 11.2 years). The ratio between patients and control group was 2.02:1. 28.1% of patients experienced developmental decline. Abnormal performance status, CBC, Electrolyte Analysis, RFT, LFT etc. were associated with increased likelihood of developmental decline. In addition, patients undergoing chemotherapy had shown significant decline in above mentioned factors than non chemo patients. Significant difference among demographic and clinical parameters and psychological factors were seen. Conclusions: Our unique findings emphasize that the intensity and extent of treatment with chemotherapy may disrupt psychological/psychosocial development as well as electrolyte imbalance and liver and renal dysfunction of pediatric AML patients. Legal entity responsible for the study: N/A Funding: Netaji Subhas Chandra Bose Cancer Research Institute Disclosure: All authors have declared no conflicts of interest. 343P Outcomes of good risk AML from a tertiary cancer centre: Is good always good? J. Ghosh, V. Seth, H. Menon Medical Oncology, Tata Memorial Hospital Centre, Mumbai, India Background: Good risk AML is defined cytogenetically by the presence of good risk cytogenetics which include t(8;21), inv 16, t(16;16) and is characterized by a significantly better outcome following standard induction chemotherapy followed by consolidation with high dose cytarabine. Many studies have shown that the outcome of Volume 27 | Supplement 9 | December 2016 344P B cell precursor acute lymphoblastic leukemia (ALL) shows similar drug response in pdx mice and the corresponding patient Z. Wang1, W. Ye2, Z. Zheng1, P. li3 R&D, Hichuang Biomedical (Chognqing) Corp., Beijing, China, 2Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Guangzhou, China, 3Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China 1 Background: Cumulative toxicities and drug resistance limit chemotherapy treatment after the first-line regimen. Tumors from patient-derived xenograft (PDX) models closely recapitulate the tumors from the same patient, regarding to their histopathological and genetic profiles. However, it is still unknown whether drug response of B-ALL in PDX mice can reflect the patient clinic outcome. In this study, pre-B ALL PDX model were established and examined to determine responses of the established leukemia to two conventional chemotherapeutic regimens. Using the PDX mice model, we compared the drug response in PDX mice with the clinic outcome of the corresponding patient. Methods: PDX models were established by being injected with pre-B ALL samples from eight patients into NOD-SCID-IL2RG-/- (NSI) mice. The PDX models of each patient were then divided into three groups that were treated with VDLP regimen (vincristineþdaunorubicinþl-asparaginasumþprednisone), HYPER-CVAD regimen (MethotrexateþcytarabineþcyclophosphamideþvincristineþAdriamycinþxamethasone), and PBS respectively. In parallel, eight patients were treated with VDLP regimen. Clinical outcomes of treated patients were collected. Results: Xenografts of pre-B ALL presented with major biological characteristics of the original cancers. 05% pre-B ALL cells in blood marrow of PDX mice is defined as complete remission; pre-B ALL cells 20% is defined as no remission. Six out of eight patients achieved complete remission after being treated with VDLP regimen. Consistently, B-ALL cells were completely eliminated after treatment of VDLP and HYPER-CVAD regimens in the PDX mice of these six patients. Two patients failed to achieve remission after VDLP treatment, whose B-ALL cells were also resistant to both VDLP and HYPER-CVAD regiments in xenografts. Conclusions: Our results demonstrate that drug efficacy assessments based on PDX mice were consistent to clinical outcomes of the patient. PDX mice may potentially serve as a tool to optimize the clinic treatment for individual therapy. Legal entity responsible for the study: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Funding: Hichuang Biomedical(Chongqing)Corp. Disclosure: All authors have declared no conflicts of interest. doi:10.1093/annonc/mdw586 | ix107 abstracts 345P Annals of Oncology A new L-asparaginase as a promising biodrug to acute lymphoblastic leukemia treatment Table: 346P L. Schultz1, G. Monteiro2, A. Pessoa-Jr2, M.A. de Oliveira1 Biology, Sao Paulo State University, Sao Vicente, Brazil, 2Biochemical and ~o Paulo, Brazil Pharmaceutical Technology, University of S~ ao Paulo, Sa Leukemia % subtypes Estimated 1-yr OS benefit Estimated 5yr OS benefit CLL AML ALL CML All Leukemia 37.8% 30.8% 13.8% 14.5% 0.02% 50.30% 18.60% 0.04% 19.4% (95% CI 19.2%-19.6%) 0.08% 29.20% 16.30% 37.60% 19.7% (95% CI 19.3%-20.0%) 1 Background: Bacterial L-asparaginases (L-ASNase) are tetrameric enzymes of high molecular weight (140kDa) used as therapeutic proteins for treatment of acute lymphoblastic leukemia (ALL), since this kind of tumor cell is dependent on the availability of extracellular L-asparagine (Asn). Bacterial L-ASNase hydrolyzes efficiently Asn into aspartate (Asp) and ammonia, decreasing the source of Asn to tumor cells. International pharmaceutical industries produce L-ASNase from Escherichia coli and Erwinia chrysanthemi, but several side effects are associated with L-ASNase administration, including immunological reactions, neurotoxicity, among others. Furthermore, its use in patients often results in a rapid decay of circulating LASNase levels, leading to high frequency of the administration. Therefore, it is essential to search new sources of this enzyme in order to increase its availability as a drug, to reduce side effects. In this context, the biodiversity is an important source to find new biopharmaceuticals. Methods: In this work we have characterized by molecular biology and biochemical approaches, a new enzyme named ASNaseS with high homology with the bacterial counterparts (50% similarity), which may be a potential alternative in the treatment of the ALL. The structure of the enzyme was characterized by circular dichroism spectroscopy (CD) and by size exclusion chromatography (SEC), the biochemical assays were performed by L-glutamic dehydrogenase-coupled spectrophotometric assay as also by colorimetric assay using Nessler’s reagent. Results: The CD data revealed an a/b structure containing 16% of a-helix and 35% of b-sheets and elevated thermoresistence (> 50 C). SEC analysis showed that enzyme possess low molecular weight (44 kDa) in solution, a very contrasting result with bacterial counterparts. Evaluation of L-ASNase activity showed that the L-ASNaseM has kcat ¼ 0.414 s1, Km ¼ 4.18 mM and kcat/Km ¼ 99 M1s1, the activity specific is 5.6 U/mg. Conclusions: The results suggest that L-ASNaseM may be a promising alternative biopharmaceutical to ALL treatment. Additionally, site-directed mutagenesis approaches aiming to improve the enzyme properties are in progress. Legal entity responsible for the study: UNESP and USP. Funding: FAPESP (S~ao Paulo Research Foundation, Proc. n.2013/08617-7). Disclosure: All authors have declared no conflicts of interest. 346P An estimation of the population survival benefit of first-course chemotherapy and immunotherapy for leukemia V. Do1, S. Jacob2, W. Ng2, G.P. Delaney2, M.B. Barton2 SWRON, The Crown Princess Mary Cancer Centre, Westmead, Australia, 2 Collaboration for Cancer Outcomes Research and Evaluation (CCORE), Ingham Institute for Applied Medical Research, University of New South Wales, Liverpool, NSW, Australia 1 Background: Randomized clinical trials describe the benefit of chemo-and immunotherapy for specific leukemia patients with selected patient and disease characteristics. The overall survival benefit for the whole population of leukemia patients in Australia if evidence-based guidelines for chemo-and immunotherapy were implemented routinely is unknown. Our study’s purpose was to estimate the overall population survival benefit of applying evidence-based practice. Methods: Decision trees with evidence-based indications for chemotherapy have been previously defined for leukemia. Each branch corresponds to a specific cohort who have, or do not have, defined indications for chemotherapy and/or immunotherapy. Chemo-and immunotherapy benefit was defined as the absolute incremental benefit of either chemotherapy and/or immunotherapy over no chemo- and/or immunotherapy for radical and palliative indications. Multiple electronic citation databases were systematically queried, including Medline and the Cochrane Library. In cases where there were multiple sources of the same level of evidence, hierarchical meta-analysis was performed. The benefits of chemo-and immunotherapy were estimated for 1, 5-year survival. To assess the robustness of our estimates, sensitivity analyses were performed. Results: The estimated 1-year and 5-year absolute population-based overall survival benefits of optimally utilized first-course chemo- and immunotherapy for leukemia in Australia are 19.4% (95% Confidence Interval (CI), 19.2%-19.6%), and 19.7% (95% CI, 19.3%-20.0%), respectively. They are summarized in the table. ix108 | abstracts Conclusions: Chemo- and immunotherapy agents improves overall survival in leukemia at 1- and 5-years. Chemo-and immunotherapy provides an important survival benefit to this patient population in Australia when it is used in accordance with guideline recommendations. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 347P Association between allergic conditions and risk of nonHodgkin lymphoma and Hodgkin lymphoma: A systematic review and meta-analysis J. Yang1, H. Xu1, P. Li2, X. Liang1, Y. Jia1 Department of Radiotherapy, Zhejiang Provincial People’s Hospital, Hangzhou, China, 2Department of Gastroenterology, 2nd Affiliated Hospital of Zhejiang University University School of Medicine, Hangzhou, China 1 Background: We aimed to systematically evaluate the association between allergic conditions and risk of hodgkin lymphoma (HL) and non-hodgkin lymphoma (NHL). Methods: Systematic literature searches in Pubmed and Embase was conducted up to October, 2015 to identify eligible studies. Either a fixed- or a random-effects model was adopted to estimate overall odds ratios (ORs) according to heterogeneity across studies. Results: A total of 24 case-control studies with 35725 NHL cases and 13 cohort studies comprising 4452 NHL cases were included in the pooled analysis of NHL risk. An inverse association was observed between history of any allergic condition and NHL risk in case-control studies (OR ¼ 0.83, 95% CI 0.76-0.91), while the reduction of NHL risk was not suggested in cohort studies (OR ¼ 1.18, 95% CI 0.98-1.42). Stratifying by type of allergic conditions, significant association with NHL risk was found for asthma, hay fever, food allergy, allergic rhinitis and hives. In the pooled analysis of HL risk, 12 studies (2 were cohort studies) with 2750 HL cases were included. The pooled OR was 0.96 (95% CI 0.84-1.09) for case-control studies and 1.46 (95% CI 0.63-3.38) for cohort studies. For specific allergic condition, we observed a reducing HL risk in individuals with hay fever and food allergy. Conclusions: Several specific allergic conditions, including asthma, hay fever, food allergy and allergic rhinitis were associated with reduced NHL risk, while hay fever and food allergy was inversely associated with HL risk. History of any allergic condition was not significantly associated with NHL or HL risk. Legal entity responsible for the study: Jia Yang Funding: N/A Disclosure: All authors have declared no conflicts of interest. 348P Real world practice patterns in multiple myeloma patients presenting with pleural effusion K.H. Kim1, J.M. Byun2, J.H. Park1, J-S. Kim1, I. Choi1, D-Y. Shin2, Y. Koh2, I. Kim2, S-S. Yoon2, H-J. Lim3 1 Internal Medicine, Boramae Medical Center, Seoul, Republic of Korea, 2Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea, 3 Department of Internal Medicine, Veterans Health Service Medical Center, Seoul, Republic of Korea Background: In many Asians countries battling with the double burden of increasing noncommunicable diseases such as multiple myeloma (MM) on top of unresolved issues of infectious diseases, MM patients presenting with pleural effusion (PE) pose a great diagnostic challenge. Thus, we aimed to devise structured approaches to care by analyzing clinical features and practice patterns of such patients in Korea. Methods: This is a multicenter retrospective study of newly diagnosed MM patients over 18 years old between January 2011 and December 2015. Among 575 MM patients Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology diagnosed during the study period, 80 (13.9%) were associated with PE. These 80 patients were selected for further analyses. Results: The median age was 63 (range 35-81), with similar gender distribution (male 55% vs. female 45%). Bilateral PE (61.2%) was more common than unilateral effusion (38.8%). There were 22 patients (27.5%) with effusion as the initial diagnosis of MM and 58 (72.5%) who developed effusion during the course of MM. Fifty-six patients underwent additional examinations to determine the exact cause of effusion; 28 patients received computed tomography (CT) of chest, 5 patients underwent thoracentesis/ biopsy, and 23 patients underwent both CT and thoracentesis/biopsy. On the other hand, 24 patients did not undergo additional analyses but treated empirically. The clinical diagnosis given to all patients are shown in the table. Table: 348P N Myelomatous Parapneumonic Organism identified Clinical diagnosis Tuberculosis Congestive heart failure Renal failure, acute and chronic Hypoalbuminemia Reactive to other general medical conditions Combined Unknown Total (%) No additional exam (%) Additional imaging (%) Invasive procedure (%) 80 7 (8.8) 20 (25.0) 9 (45.0) 11 55.0) 2 (2.5) 9 (11.2) 24 (30.0) 0 3 (12.5) 0 3 (100) 0 4 (16.7) 28 (35.0) 0 10 (35.7) 4 (40) 6 (60) 0 1 (3.6) 28 (35.0) 7 (25.0) 7 (25.0) 5 (71.4) 2 (28.6) 2 (2.5) 4 (14.3) 7 (8.8) 4 (16.7) 3 (10.7) 0 9 (11.2) 15 (18.8) 4 (16.7) 7 (29.2) 4 (14.3) 5 (17.9) 1 (3.6) 3 (10.7) 9 (11.2) 2 (2.5) 1(4.2) 1 (4.2) 4 (14.3) 1 (3.6) 4 (5.0) 0 Conclusions: Real world analyses of practice pattern in MM patients with PE showed suboptimal use of invasive procedures to determine the exact cause of PE. Since myelomatous effusion and tuberculosis pleurisy are not uncommon in Korea, when in doubt invasive procedures should be actively recommended. Legal entity responsible for the study: Seoul Metropolitan Government Seoul National University Boramae Medical Center Funding: Seoul Metropolitan Government Seoul National University Boramae Medical Center Disclosure: All authors have declared no conflicts of interest. 349P A retrospective multicenter survey of hepatitis B virus infection (HBV) screening and HBV-DNA monitoring in patients receiving hematopoietic stem cell transplantation and rituximab-based chemotherapy T. Nakashima1, Y. Ohashi2, S. Oki3, R. Saito4, K. Koido1, C. Ogawa2, N. Sato2, K. Seto3, Y. Negishi4, N. Kondo3, M. Kikuchi5, A. Yokoyama6, H. Ueno6, M. Koinuma7, Y. Yachi2, H. Terakado1 1 Pharmacy, National Cancer Center Hospital, Tokyo, Japan, 2Pharmacy, National Hospital Organization Tokyo Medical Center, Meguro-ku, Japan, 3 Pharmacy, National Center for Global Health and Medicine, Tokyo, Japan, 4 Pharmacy, National Hospital Organization Shibukawa Medical Center, Shibukawa, Japan, 5Division of Gastroenterology, National Hospital Organization Tokyo Medical Center, Meguro-ku, Japan, 6Devision of Hematology, National Hospital Organization Tokyo Medical Center, Meguro-ku, Japan, 7Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Nakanoku, Japan Background: In Japanese clinical practice, the actual conditions for screening and monitoring of HBV reactivation in patients receiving high-risk therapies such as rituximab (R)-based chemotherapy and hematopoietic stem cell transplantation (HSCT) are not well understood. Methods: At four institutes belonging to national hospital organizations or national centers in Japan, between January 2011 and December 2012, the screening status of HBV infection and frequency of HBV-DNA monitoring were determined in patients with hematological malignancy, who had recently received R-based chemotherapy or HSCT. In patients who exhibited seropositive screening tests, the clinical features of Volume 27 | Supplement 9 | December 2016 HBV reactivation and hepatitis were analyzed until December 2015 (last follow-up date). Results: Of the 491 and 265 study patients who received treatment with R-based chemotherapy and HSCT, respectively, 416 (84.7%) and 254 (95.8%) were screened properly prior to treatment. The number of HBV patients receiving the aforementioned respective treatments who exhibited screening test seropositivity was 104 (25.0%) and 46 (18.1%), which comprised 16 (3.8%) and 4 (1.6%) patients with HBsAg positive and 88 (21.2%) and 42 (16.5%) patients with past HBV infection. HBV reactivation occurred in 6 and 4 patients with past HBV infection, respectively. Severe HBV-related hepatitis (alanine aminotransferase >10-fold of the upper limit of normal) occurred in 1 patient receiving HSCT, and there was no hepatitis-related mortality during the study period. The median duration of HBV reactivation from treatment initiation or the day of transplantation was 13.5 months (range: 4–22) and 17 months (range: 3–34), respectively. Conclusions: In our study, the proportion of screening was higher than that reported previously, but serial HBV-DNA monitoring was not always sufficient. Because lateonset HBV reactivation occurred more often, especially post-HSCT, longer-term monitoring of HBV-DNA is necessary in these populations. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 350P Single center experience of diffuse large b-cell lymphoma patients with central nervous system relapse F. Qureshi Medical Oncology, Shaukat Khanum Memorial Cancer Hospital and Reserch Centre (SKM), Lahore, Pakistan Background: Central nervous system (CNS) relapse of diffuse large B cell lymphoma (DLBCL) is relatively uncommon and nearly fatal. We analyzed characteristics of patients of DLBCL presenting with CNS relapse. Methods: All patients of DLBCL with CNS relapse from January 2010 to December 2015 were included. Data were collected from hospital information system and analyzed for characteristics and median survival. Results: Twenty one patients were included in the study; 14 (66.3%) males and 7 (33.7%) were females. At the time of initial diagnosis of DLBCL, median age was 37.4 years. Twelve (57.1%) patients had stage IV; 4 (19.0%), 2 (9.5%) and 3 (14.3%) had stage III, II, I disease respectively. There was extra-nodal involvement in 16 (76.2%), high LDH in 18 (85.7%), bone marrow involvement in 8 (38.1%) and bulky disease in 5 (23.8%) patients. The calculated International Prognostic score (IPS) was 1 in 4 (19%), 2 in 9(42.9%) 3 in 8 (38.1%). Lymph nodes were involved in 11 (54.5%) patients, followed by gut involvement in 2 (9.1%), cervix in 1(4.5%), gluteal muscle in 1 (4.5%), iliac bone in 1 (4.5%), liver in 1 (4.5%), ovaries in 1(4.5%), pancreas in 1(4.5%), parotid gland in 1 (4.5%) and testes in 1 (4.5%) patients. Sixteen patients received CHOP and six received RCHOP chemotherapy. Ten (47.6%) patients received CNS prophylaxis with intrathecal methotrexate. After completion of therapy 10 (47.6%) shows complete response, 3 (14.3%) partial response and 8 (38.1%) progressed. Ten (81%) patients had relapse within 6 months after completion of chemotherapy. Seven (33.3%) patients had isolated CNS relapse. Median overall survival in all CNS relapse patients was 54 days. Conclusions: DLBCL patients, developing CNS relapse had advanced stage, high LDH and extra-nodal involvement at initial presentation with short overall survival. Legal entity responsible for the study: Shaukat Khanum Memorail Cancer Hospital Funding: N/A Disclosure: F. Qureshi: It was retrospective analysis of patients, no financial interest. 351P Clinico-pathologic profile and clinical outcomes of patients with indolent lymphoma at the Cancer Institute of the Philippine General Hospital: A 7-year experience P.R. Dela Rosa1, C.V. Uy1, J. Tindoc2, C. Ngelangel1 Medicine, Philippine General Hospital, Manila, Philippines, 2Pathology, Philippine General Hospital, Manila, Philippines 1 Background: Indolent lymphoma (IL) is a slowly growing lymphoma, generally refractory to conventional chemotherapy. There are several types of IL, which includes Follicular lymphoma, Marginal Zone lymphoma, Small Lymphocytic lymphoma, Mantle Cell lymphoma, and Waldenstrom Macroglobulinemia/Lymphoplasmacytic lymphoma. Presently, there are no known data in the Philippines on IL. This study is done to determine the clinico-pathologic profile and outcomes of Filipino patients with IL. Methods: This study is a retrospective chart review of outpatient department cases of IL seen at the Philippine General Hospital-Cancer Institute from January 2009 to January 2016. The following were documented: age; gender; initial complaint; presence or absence of B symptoms; sites involved; type of IL; Ann-arbor stage; prognostic indices doi:10.1093/annonc/mdw586 | ix109 abstracts for FL and MCL; and if bone marrow aspiration or complete whole body CT scan were done as part of initial staging. Treatment intervention and clinical outcomes were documented. Fischer’s exact test at p < 0.05 was used to determine the association between select parameters and outcomes. Results: This study showed that Small Lymphocytic lymphoma was the most common IL. Most were elderly (>40 years old); male; without B symptoms; limited disease; and initial complaint related to the eye. MCL were seen in all risk groups, and positive for cyclin D1; FL were mostly grade 1, and positive for BCL2 and CD10. Majority had disease control regardless of treatment intervention. Most patients with recurrence/progression after initial treatment had limited disease and incompletely staged. There seemed to be no association between age, gender, stage, complete whole body CT scan/bone marrow aspiration with clinical outcomes, although the sample size examined was small. Conclusions: Results of this study are mostly consistent with known literature on IL. Absence of B symptoms and limited disease may indicate a low-grade histology. Observation remained the intervention of choice for patients who were asymptomatic. Legal entity responsible for the study: Paolo R. dela Rosa Funding: Self-funded by the authors Disclosure: All authors have declared no conflicts of interest. Annals of Oncology infradiaphragmatic as well as disease on both sides of the diaphragm. Most of the patients (93.2%) received either CHOP or R-CHOP chemotherapy. Consolidative radiotherapy was received by 43(58.1%) patients. Median follow-up period was 22 months (range 2-147 months). Complete response was seen in 51(68.9%) patients. With addition of radiation, 9.4% improvement in local control was seen. Relapses was seen in 10(13.5%) patients, out of which 5(6.8%) had nodal and 5(6.8%) had visceral relapse. At 2-years, disease free survival (DFS) and overall survival (OS) was 66% and 81.5% respectively. Stage, International prognostic index (IPI), supradiaphragmatic disease, number of sites, extranodal diasease and number of nodal sites involvement were important prognostic factors having significant impact on response, DFS and OS. Conclusions: This study represents the largest Indian experience to treat DLBCL. Stage, IPI, supradiaphragmatic disease, number of sites, extranodal disease and number of nodal sites were the important prognostic factors for response, DFS and OS. Legal entity responsible for the study: PGIMER Funding: PGIMER Disclosure: All authors have declared no conflicts of interest. 354P 352P The role of radiotherapy in early-stage primary diffuse large B-cell lymphoma of the Waldeyer’s Ring: A retrospective cohort study S.F. Lee Clinical Oncology, Tuen Mun Hospital, Tuen Mun, Hong Kong, China Background: The role of radiotherapy (RT) in improving survival of patients with diffuse large B-cell lymphoma (DLBCL) of the Waldeyer’s ring (WR) remains controversial. Therefore, this retrospective cohort study aimed to determine the role of RT in the treatment of DLBCL of the WR and the effects of covariates. Methods: Patients (n ¼ 35) with Stage I–II DLBCL of the WR, who were receiving treatment at our center between 1994 and 2010, were retrospectively investigated. All patients had histological diagnosis and staging workup completed. Kaplan-Meier curves of overall survival (OS), event-free survival (EFS), and disease-free survival were plotted and compared using a log-rank test. Log-rank tests and a univariate Cox proportional hazards model were used to compare categorical and continuous variables, respectively. Variables with a P-value of < 0.1 were included in the multivariate Cox proportional hazards model. Results: The median OS was 8.1 years. The 5-year OS rate was significantly higher in the RT group than in the non-RT group (65.4 versus 36.4% respectively; P ¼ 0.008). On multivariate analysis, RT was associated with improved OS (hazard ratio [HR]: 0.15, 95% confidence interval [CI]: 0.04–0.50; P ¼ 0.002) and EFS (HR: 0.29, 95% CI: 0.095– 0.86; P ¼ 0.026). An Eastern Cooperative Oncology Group performance status >1 and age >60 years were also found to negatively influence OS and EFS. Conclusions: RT was associated with improved OS and EFS in Stage I–II DLBCL of the WR. Future prospective studies are required to confirm these findings. Legal entity responsible for the study: Tuen Mun Hospital Funding: This study was supported by Tuen Mun Hospital Disclosure: All authors have declared no conflicts of interest. 353P Survival trends of primary testicular diffuse large B-cell lymphoma: A population-based study M. Mousa, A. Meshref Faculty of Medicine, Suez Canal University, Ismailia, Egypt Background: Primary Testicular lymphoma is considered a rare disease with a limited data on its survival trends and outcomes of treatment. In our study, we aimed at evaluation of 5-year relative survival rates of these patients in a large sample using the Surveillance, Epidemiology, and End Results (SEER) Registry of the United States. Methods: Kaplan-Meir method was used to analyze the 5-year relative survival rates of 1074 primary testicular diffuse large B-Cell lymphoma cases using SEER*Stat Program. Relative survival rates were calculated using Z-test among groups of patients categorized by year of diagnosis, race, age groups and laterality. Results: We found a statistically significant increase in the relative survival rates in the group of patients diagnosed in and after the year of 2000 which is the year of introduction of rituximab to the treatment protocols (66.8% 6 2.6%) in comparison to patients diagnosed before the year of 2000 (54.1% 6 3.3%, P ¼ 0.005). When the study population was categorized according to age at diagnosis (18-59, 60-69, 70-79 and older than 80 years old) the 5-year relative survival rates were 96.5%, 62.7% 59.9% and 46.1% respectively (P < 0.001). In terms of laterality, there was a statistically significant increase in the relative survival rate of unilateral tumors (62.9% 6 2.1%) in comparison to bilateral tumors (48.3% 6 8.1, P ¼ 0.009). The study results didn’t show a significant difference in relative survival rates when the cases were categorized in term of race. Conclusions: The introduction of rituximab to the treatment protocols, younger age at the time of diagnosis and unilateral tumors seems to have better relative survival rates in such cases. Such results can be used in reforming the disease surveillance and prognostic counseling programs in a better manner. Legal entity responsible for the study: The Surveillance, Epidemiology, and End Results (SEER) Program of the American National Cancer Institute Funding: Suez Canal University Disclosure: All authors have declared no conflicts of interest. 355P Outcome and prognostic factors in diffuse large B-cell lymphoma Lower radiotherapy dose in patients with Hodgkin’s lymphoma- is it comparable to the past standard? R. Mahajan1, B.S. Yadav1, S. Kumar1, A. Gupta1, S. Ghoshal1, S.C. Sharma2, N. Kumar1, R. Kapoor1 1 Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, 2Radiotherapy and Oncology, MMIMSR, Mullana, Ambala, India B.S. Yadav1, S.C. Sharma1, N. Kumar1, S. Ghoshal2 Radiation Oncology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, 2Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India Background: Diffuse large B-cell lymphoma (DLBCL) is the most common nonHodgkin’s lymphoma(NHL). We conducted retrospective study in our institution to analyze the main clinical features at diagnosis, response to therapy and the outcome of patients with DLBCL. Methods: This study enrolled 74 patients with histologically confirmed diagnosis of DLBCL treated from January 2003 to December 2014. Complete clinical patient and disease related details were recorded. All patients were treated with chemotherapy with or without radiotherapy. Clinical features, treatment response and impact of different prognostic factors on clinical outcome were analyzed. Bulky disease was defined as any mass greater than 10cm in diameter. Results: Median age of presentation was 50 years (range 18-85 years). Out of 74 patients, 53 were males and 21 were females. Ann Arbor clinical stage at diagnosis was 36(48.6%) stage I, 20(27%) stage II, 13 (17.6%) stage III, and 5(6.8%) stage IV respectively. Bulky disease was present in 6 patients (8.1%). Nodal disease was present in 40(54.1%) patients and 34(45.9%) had extranodal disease presentation. Supradiaphragmatic disease was seen in 44(59.5%) and 15(20.3%) had Background: Hodgkin’s lymphoma patients survive longer so there is always of risk late term toxicity in these patients. The current trials are focussing to reduce number of chemotherapy cycles and radiation dose in these patients. Here we report our analysis of lower radiotherapy (RT) dose and compared it to the past standard in our setup. Methods: From 2001 to June 2014, 170 patients with stage I to IV HL treated with combined modality or radiation alone were analyzed. Radiotherapy was given to 84(49%) patients; IFRT to 79(94%) and EFRT to 5(6%) patients respectively. We compared outcome of patients who received 30 Gy RT dose to those with 36Gy. Outcome compared were relapse rate, disease free survival (DFS) and overall survival (OS). DFS and OS were estimated using Kaplan-Meier method. Results: RT dose of 30 Gy was delivered to 36 patients and 36Gy to 48 patients. Mean age was 26 years(range 6-65 years). Median follow up was 44 months (range 9-210 months). Relapse was seen in 3(8.3%) patients with 30 Gy and were outside the RT field in all patients. In patients with 36Gy, relapse occurred in 6(12.5%) patients, with in RT field in 1 patient and outside in 5 patients respectively. DFS at 5 years was not statistically different with 30 Gy or 36Gy, 89% vs 84% respectively(p ¼ 0.40). Similarly ix110 | abstracts 1 Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology OS at 5 years was not statistically different with 30 Gy or 36Gy, 96% vs 92% respectively(p ¼ 0.34). Conclusions: In patients with Hodgkin’s lymphoma relapse rate DFS an OS were comparable RT dose of 30 Gy and 36 Gy. Future study will focus to further reduce the RT dose in these patients. Legal entity responsible for the study: IEC Funding: PGIMER Disclosure: All authors have declared no conflicts of interest. 356P Early stage natural killer/T cell lymphoma with local tumor invasiveness treated with a uniform SMILE protocol: An institutional study from India V.G. Gupta1, A. Gogia1, P. Mehta1, L. Kumar1, A. Sharma1, S. Bakhshi1, S. Thulkar2, M.C. Sharma3, S. Mallick3, R.K. Sahoo1, P. Malik1 1 Medical Oncology, Dr. BRA Institute Rotary Cancer Hospital (AIIMS), New Delhi, India, 2Radiodiagnosis, Dr. BRA Institute Rotary Cancer Hospital (AIIMS), New Delhi, India, 3Pathology, All India Institute of Medical Sciences, New Delhi, India Background: Local Tumor Invasiveness (LTI) is among the strongest prognostic factors in Early Stage Nasal Natural Killer/T Cell Lymphoma (ES-NNKTCL), with very poor outcomes. Standard therapy is concurrent or sequential chemotherapy and radiotherapy (RT). SMILE (Dexamethasone, Methotrexate, Ifosfamide, L-asparaginase and Etoposide) is an intensive, highly active protocol in this disease. No prior study has explored SMILE with RT specifically for ES-NNKTCL with LTI. Methods: Between 2011 and 2015, all patients with ES-NNKTCL with LTI at our center were treated with a uniform protocol of SMILE for 6 cycles with sandwiched RT (45-50 Gray). LTI was defined as bony invasion/destruction or involvement of the skin. Records of these patients were retrospectively reviewed. Results: Sixteen patients (62% male) were identified with median age 31 years (range 19-55). Eleven (69%) were stage I and 5 (31%) were stage II. Facial skin involvement (56%), palatal invasion (69%), or orbital extension (56%) were present in the majority. 12/16 had B-symptoms, and 6/16 had elevated lactate dehydrogenase. International prognostic index was 0, 1, and 2 in 56%, 19% and 25% respectively. Korean prognostic score was 0, 1, 2, and 3 in 19%, 38%, 31% and 12% respectively. All patients received 5-6 cycles (Five patients received 5 cycles, the rest received 6 cycles) barring those who progressed on therapy. RT was delivered after a mean 4 6 1 cycles. At a median follow up of 14.5 months (range 2-63), 2/16 patients are still on therapy. Among the remaining 14, two patients (14%) relapsed while on therapy. Rest all achieved complete remission at the end of the treatment (86%). For the entire cohort, one year progression-free survival was 78% and overall survival was 93%. Grade III-IV toxicity was seen in 81%, most commonly neutropenia (69%), anemia (38%) and thromobocytopenia (31%). Neutropenic fever was seen in 25% despite growth factor prophylaxis. Six patients (38%) required dose adjustments (predominantly in the first 1 or 2 cycles). No treatment-related deaths occurred. Conclusions: SMILE with RT is a toxic but tolerable protocol for ES-NNKTCL with LTI with high efficacy. Prospective studies are warranted. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 357P Targeting dual metabolic pathway specifically killed malignant lymphoma cells T. Wang, X. Shao, B. Xu, H. Huang, F. Chen Hematology, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China Background: The metabolic reprogramming is a remarkably different metabolic character among tumor cells and is linked to higher proliferation, stronger resistance to chemotherapy, more adaptive survival advantages and aggressive tumor progression. Malignant tumor cells prefer glycolysis rather than aerobic oxidation even under aerobic surroundings. Furthermore, this altered metabolism is an active adjustment regulated by PI3K/Akt/mTOR pathway, HIF-1a and c-MYC in a reversible manner. Volume 27 | Supplement 9 | December 2016 Methods: Raji and SU-DHL4 cells were treated with different concentrations of rapamycin or oligomycin alone or the two drugs in combination. Cell proliferation was detected by CCK-8. The mRNA and protein expression levels of oncogene C-myc, hypoxia inducible factor-1a (HIF-1a), as well as key enzymes and proteins related to glycolysis pathway including hexokinase II (HKII), lactic dehydrogenase (LDHA) and succinate dehydrogenase (SDHA) were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. Glucose consumption and lactic acid generation were examined by Glucose (hexokinase, HK) Assay Kit and Lactate Assay Kit, respectively. Apoptosis and cell cycle distribution were analyzed by FCM. Results: The mTORC1 inhibitor rapamycin (RAPA) and the proteasome inhibitor bortezomib (BTZ) hampered glycolysis in malignant B-cell lymphoma cells successfully. Either glycolysis inhibitors RAPA and BTZ or the aerobic oxidation inhibitor oligomycin (OM) selectively inhibited the proliferation of Raji and SU-DHL4 cells in a dose-dependent manner. In contrast, no difference was observed in normal lymphocytes. Furthermore, rapamycin and oligomycin combined with doxorubicin or bortezomib in combination with oligomycin, indicating attenuating both the glycolysis and the aerobic oxidation pathway at the same time, synergistically inhibited cell proliferation and induced cell apoptosis, and thus increased the sensitivity of malignant B-cell lymphoma cells toward doxorubicin and bortezomib, via blocking the dual metabolism. Synergistically inhibition on mRNAs and proteins (HIF-1a, HKII, LDHA, SDHA) was involved. Conclusions: Inhibiting the dual metabolic pathway may provide a novel strategy to cure malignant B-cell lymphoma. Legal entity responsible for the study: Renji Hospital, Shanghai Jiaotong University School of Medicine Funding: National Natural Science Foundation of China (NSFC), Grant 81172253, Grant 81570177 Disclosure: All authors have declared no conflicts of interest. 358P PPAR GAMMA Agonist in combination with BCR/ABL TKI in patients of CML-CP with suboptimal molecular response H. Malhotra1, B. Malhotra2, A. Yadav3, A. Mathur3, D. Biswas2 Medicine & Medical Oncology, SMS (Sawai Man Singh) Medical College & Attached Hospital, Jaipur, India, 2Microbiology, SMS (Sawai Man Singh) Medical College & Attached Hospital, Jaipur, India, 3Medicine, SMS (Sawai Man Singh) Medical College & Attached Hospital, Jaipur, India 1 Background: Approximately 10 to 20% of patients of CML in chronic phase (CML CP) have suboptimal molecular response (MR) to first line Imatinib maleate (IM) treatment. Failure to achieve a complete MR results from the inability of TKIs to eradicate quiescent CML leukaemia stem cells (LSCs). Treatment options for these patients include increasing the dose of IM or switch to a second generation TKI (Nilotinib or Dasatinib). Recently, the addition of PPAR gamma agonists (glitazones) toTKIs has been shown to be toxic to the CML stem cells and the combination to products stem cell depletion. In the present study we report our initial results on 12 patients of CML CP in complete hematological response (CHR) who showed suboptimal molecular response to IM/2nd gen. TKI (as per ELN criteria) and were treated with the combination of TKI plus pioglitazone. Methods: Twelve patients of CML-CP in CHR but not in major MR (BCR/ABL ABL IS ratio between 1% to 10%) were included in the study. All patients were given Tab. Pioglitazone 30 mg. OD. PO in addition to the TKI. CBC, biochemistry was done every month and BCR/ABL levels on international scale (IS) were estimated every 3 monthly. Results: Eight patients were on Imatinib maleate (IM) 600 mg OD while 4 patients were on Nilotinib 400 mg. BD. After a mediam follow up of 6 months, 11 of the 12 patients showed a more than 50% decrease in the BCR/ABL ABL ratio, 4 out of the 12 showed a more tha one log decrease and 2 patients had undetectable levels of BCR ABL at the end of 6 months. The combination was well tolerated with only one patient having transient grade I transaminitis which resolved without drug dose decrease or stoppage. Conclusions: Our priliminary results of this small pilot study indicate that the combination of PPAR gamma agonist, pioglitazone, with a BCR ABL TKI is effective in reducing BCR ABL transcript levels in patients of CML-CP who have not acheived a CMR. The combination is associated with minimal toxicity. Further, larger studies are needed to confirm these findings. Legal entity responsible for the study: RK Birla Cancer Center, SMS Medical College & Hospital, Jaipur, India Funding: Cancer Education & Research Trust Disclosure: All authors have declared no conflicts of interest. doi:10.1093/annonc/mdw586 | ix111 Annals of Oncology 27 (Supplement 9): ix112–ix122, 2016 doi:10.1093/annonc/mdw587 Head and neck cancer 359O_PR Efficacy and safety of pembrolizumab (MK-3475) in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): Subset analyses for Asia-pacific patients in KEYNOTE-012 (KN-012) B2 cohort abstracts M. Tahara1, K. Muro2, Y. Hasegawa3, H.C. Chung4, C-C. Lin5, B. Keam6, J. Cheng7, Y-J. Bang8 1 Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan, 2Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, 3Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan, 4Medical Oncology, Yonsei Cancer Center, Seoul, Republic of Korea, 5Oncology, National Taiwan University Hospital, Taipei, Taiwan, 6Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea, 7Merck Research Laboratories, Merck Sharpe and Dohme, Kenilworth, NJ, USA, 8Medical Oncology, Seoul National University Hospital, Seoul, Republic of Korea Background: The PD-1 pathway is a key mechanism by which R/M HNSCC tumors evade immune surveillance. MK-3475, an anti–PD-1 antibody, shows promising antitumor activity in R/M HNSCC in KN-012 (NCT01848834). We present a subset analysis for long-term follow-up of the efficacy and safety of MK-3475 in Asia-pacific R/ M HNSCC patients (pts) Methods: Pts had R/M HNSCC, measurable disease by RECIST v1.1, and ECOG PS 0-1. Pts were enrolled regardless of PD-L1 status. MK-3475 200 mg Q3W was given for 24 months (mo) or until disease progression, unacceptable safety, or investigator/pt decision. Response was assessed every 8 weeks. AEs were graded using CTCAE v4.0. The primary end point was ORR per central imaging vendor review. Secondary end points included PFS, OS, and duration of response (DOR). Pts who received 1 dose of MK-3475 were included in these pooled analyses. Results: Out of 132 pts in KN-012 B2 cohort, 26 Asia-pacific R/M HNSCC pts were enrolled and received MK-3475. 3 (12%) pts were still on treatment as of April 26, 2016. Median age was 61.5 y; 85% were male; 65% had ECOG PS 1; 62% received 2 lines of chemotherapies for recurrent disease. ORR (confirmed) was 19.2% (95% CI, 6.6%39.4%; no CR, 5 PRs). 8 (30.8%) pts achieved stable disease. Median follow-up duration in responders was 19.4 mo (range, 18.4-20.6). At the data cutoff, median DOR was not yet reached (range, 5.8 to 16.8þ mo); responses were ongoing in 4 (80%) pts. Responses of 6 mo and 12 mo were noted in 4 pts and 3 pts. Median OS was 11.6 mo (95% CI, 4.7-17.7.). The 6-mo PFS and OS rates were 20.0% and 58.5%, respectively. Treatmentrelated AEs (TRAEs) occurred in 16 (62%) pts; 2 (8%) pts had a grade 3-4 TRAE. No death due to a TRAE was observed. Conclusions: Robust antitumor activity with durable responses and promising survival suggested that MK-3475 200 mg Q3W is an active treatment in Asia-pacific R/M HNSCC pts. MK-3475 was safe and well tolerated in Asia-pacific R/M HNSCC pts. Clinical trial indentification: NCT01848834 Legal entity responsible for the study: Merck Sharp and Dohme Funding: Merck Sharp and Dohme Disclosure: J. Cheng: Employee of Merck Sharpe and Dohme. All other authors have declared no conflicts of interest. 360O_PR Efficacy and safety of nivolumab for recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) in Asia: CheckMate 141 subgroup analysis Y. Hasegawa1, N. Kiyota2, S. Takahashi3, T. Yokota4, C-J. Yen5, S. Iwae6, Y. Shimizu7, R-L. Hong8, M. Goto9, Y. Namba10, R.L. Ferris11, M. Monga12, M. Lynch13, S. Hagihara14, M. Tahara15 1 Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan, 2 Department of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan, 3Cancer Chemotherapy Center, Cancer Institute Hospital of JFCR, Tokyo, Japan, 4Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan, 5Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, 6Department of Head and Neck Surgery, Hyogo Cancer Center, Akashi, Japan, 7Department of Medical Oncology, Hokkaido University Hospital, Sapporo, Japan, 8Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, 9Cancer Center, Cancer Chemotherapy Center, Osaka Medical College, Takatsuki, Japan, 10 Clinical Development, Ono Pharmaceutical CO., LTD., Osaka, Japan, 11 Department of Otolaryngology, University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA, USA, 12Global Clinical Resarch Oncology, Bristol-Myers Squibb, Princeton, NJ, USA, 13Oncology Global Clinical Research, Bristol-Myers Squibb, Wallingford, CT, USA, 14Statistical Analysis Data science, Ono Pharmaceutical CO., LTD., Osaka, Japan, 15Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan Background: The median overall survival (OS) for patients (pts) with platinumrefractory R/M SCCHN is 6 months (mo). Nivolumab (nivo), an anti-PD-1, fully human IgG4 monoclonal antibody, demonstrated OS benefit compared to investigator’s choice (IC) therapy in CheckMate 141 (pts with platinum-refractory R/M SCCHN). Here we present a subgroup analysis of CheckMate 141 in Asian countries. Methods: The phase 3, open-label CheckMate 141 trial enrolled pts aged 18 years with R/M SCCHN and ECOG performance status 1. Pts were randomized 2:1 to receive nivo or IC (methotrexate, docetaxel, or cetuximab) until disease progression or toxicity. Primary endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate per RECIST 1.1, and quality of life. Results: Globally, 361 pts were randomized, 34 (9.4%) of whom were in Asia (27 in Japan, 5 in Taiwan, 1 in Korea, 1 in Hong Kong). At the time of analysis, globally there were 133 (55.4%) and 85 (70.2%) deaths in the nivo and IC arms, respectively, and in Asia 7 (30.4%) and 6 (54.5%) deaths, respectively. OS and PFS are reported in the table. In the nivo arm, the incidence of treatment-related adverse events (TRAEs) of any grade was 58.9% globally and 69.6% in Asia; grade 3–4 TRAEs occurred in 13.1% and 8.7% of pts, respectively. No treatment-related deaths were reported in Asia. Conclusions: The efficacy and safety profiles of nivo in platinum-refractory R/M SCCHN in Asian countries were similar to those in the global population. Nivo is the first immunotherapy to demonstrate a significant improvement in survival for pts with R/M SCCHN who progress after platinum-based therapy and is likely to become a standard of care option for R/M SCCHN in Asia. Table: 360O_PR Overall survival and progression-free survival in CheckMate 141: Globally and in Asian countries Nivolumab Investigator’s Choice Overall Survival, median (95% CI), months Global 7.5 (5.5–9.1) 5.1 (4.0–6.1) Hazard Ratio (95% CI) 0.70 (0.51–0.96)a P ¼ 0.0101 0.50 (0.17–1.48) Asian countries 9.5 (9.1–NR) 6.2 (2.6–NR) Progression-Free Survival, median (95% CI), months Global 2.0 (1.9–2.1) 2.3 (1.9–3.1) 0.89 (0.70–1.1) P ¼ 0.3236 Asian countries 1.9 (1.6–7.5) 1.8 (0.4–6.1) 0.57 (0.25–1.33) a 97.73% CI. NR, not reached. C European Society for Medical Oncology 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V All rights reserved. For permissions, please email: [email protected]. abstracts Annals of Oncology Clinical trial indentification: NCT02105636;Study start date, May 2014 Legal entity responsible for the study: Ono Pharmaceutical Funding: Funded by BMS and Ono Pharmaceutical Disclosure: N. Kiyota: Personal fees from ONO (honorarium and research funding) during the conduct of the study payment for seminar presentation from Bristol-Meyers Squibb, Merck Serono and Bayer. Y. Namba, S. Hagihara: Employee of Ono Pharmaceutical. R.L. Ferris: Grants and other from AstraZeneca, grants and other from Merck, other from Pfizer, grants and other from BMS, outside the submitted work. M. Monga: Employee of BMS. M. Tahara: Personal fees from Bristol-Myers Squibb, Merck Sharp & Dohme, Bayer, Otsuka, grants from, Boehringer Ingelheim, Novartis, NanoCarrier, grants and personal fees from Ono Pharmaceutical, Astra Zeneca, Pfizer, Eisai. All other authors have declared no conflicts of interest. 361O Patient-reported outcomes (PROs) in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) treated with nivolumab (Nivo) or Investigator’s Choice (IC): CheckMate 141 N. Kiyota1, K. Harrington2, R.L. Ferris3, J.W. Shaw4, F. Taylor5, M. Derosa5, D. Turner-Bowker5, L. Morrissey5, K. Cocks6, M. Gillison7, J. Guigay8 1 Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan, 2 Division of Cancer Biology, Royal Marsden NHS Foundation Trust/The Institute of Cancer Research, London, UK, 3Otolaryngology, University of Pittsburgh Medical Center and Cancer Institute, Pittsburgh, PA, USA, 4Worldwide Health Economics, Bristol-Myers Squibb, Princeton, NJ, USA, 5Patient-Centered Outcomes, Adelphi Values, Boston, MA, USA, 6Patient-Centered Outcomes, Adelphi Values, Bollington, UK, 7Department of Medicine, The Ohio State University, Columbus, OH, USA, 8Centre Antoine Lacassagne, Nice, France Background: Patients (pts) with platinum-refractory R/M SCCHN have median survival 6 mo and suffer from their disease and its treatment. Accordingly, maintaining quality of life (QoL) is a key treatment goal. PRO data were collected as exploratory endpoints in CheckMate 141 (NCT02105636), a randomized, open-label, phase 3 trial comparing nivo to IC (methotrexate, docetaxel, or cetuximab) in 361 pts with platinum-refractory R/M SCCHN. We report the first comparative results for PRO for nivo and IC in R/M SCCHN. Methods: The European Organisation for Research and Treatment of Cancer QoL Questionnaire (EORTC QLQ-C30), EORTC Head and Neck Cancer module (QLQH&N35), and EQ-5D were administered at baseline (BL), wk 9, and then at 6-wk intervals during treatment. A clinically relevant score change or difference was regarded as 10 points for the EORTC subscales. Analysis of covariance (ANCOVA) was applied to compare mean score changes between arms. Proportional hazards regression was used to evaluate time to clinically relevant score deterioration (TTD). Results: BL questionnaire completion rates for nivo and IC were 80% and 75%, respectively. Low IC completion rates precluded analysis of mean differences after wk 15. Overall, 129 pts completed a PRO measure at BL and during follow up. Nivo significantly delayed TTD (P < 0.05, 2-tailed) vs IC for global health; physical, role, cognitive, and social functioning; fatigue; dyspnea; and insomnia (EORTC QLQ-C30) as well as pain; sensory problems; and mouth opening problems (QLQ-H&N35). ANCOVA revealed statistically significant, clinically relevant differences favoring nivo at wks 9 and 15 for role and social functioning, fatigue, dyspnea, and appetite loss (EORTC QLQ-C30) as well as pain and sensory problems (QLQ-H&N35). Differences in mean values were observed for other PROs at wk 15 only. Conclusions: Pts treated with nivo had delayed worsening of functioning and symptoms with PRO differences between arms favoring nivo up to 4 mo of follow up. These results, as assessed through wk 15, suggest that pts receiving nivo maintained functioning for longer and had less pain, fatigue, and dyspnea on treatment as compared with IC. Clinical trial indentification: NCT02105636; Study start date, May 2014 Legal entity responsible for the study: Bristol-Myers Squibb Funding: Bristol-Myers Squibb Disclosure: N. Kiyota: Grants from research funding, Ono Pharmaceutical Co. Ltd, Eisai Co. Ltd, and Nippon Boehringer Ingelheim Co. Ltd; personal fees (honorarium and research funding), Ono Pharmaceutical Co. Ltd; payment for seminar presentation, BMS, Merck Serono, and Bayer. K. Harrington: Fees paid to research institution by BMS; personal fees from and fees paid to research institution by Merck and Amgen; personal fees from AstraZeneca and Pfizer. R.L. Ferris: Personal fees and advisory board member, Merck and Celgene; grants, personal fees and advisory board member, AZ/Medimmune and BMS; and grants, VentiRx. J.W. Shaw: Employee and shareholder, Bristol-Myers Squibb. F. Taylor: Employee of Adelphi Values, a consulting company that is being paid by BMS to analyze clinical trial PRO data. D. TurnerBowker: Employee of Adelphi Values, which received funding to conduct this research. L. Morrissey: Employee of Adelphi Values, which was paid for the statistical analyses. K. Cocks: Employee of Adelphi Values, which consults with BMS. M. Gillison: Consulting for BMS, Lilly and Merck Inc. J. Guigay: Grants and advisory board member, Merck; grants, GlaxoSmithKline; advisory board member, Bristol-Myers Squibb and Innate Pharma. All other authors have declared no conflicts of interest. Volume 27 | Supplement 9 | December 2016 362PD Development and validation of a nomogram to predict the probability of recurrence in patients with major salivary gland cancers C-Y. Hung1, C-H. Lu2, C-T. Liu3, P-H. Chang4, K-Y. Yeh4, S-H. Li3, Y-C. Lin5, T-S. Yeh6, Y-S. Hung5, W-C. Chou5 1 Department of Hematology-Oncology, Mackay Memorial Hospital, New Taipei City, Taiwan, 2Department of Medical Oncology, Chang Gung Memorial Hospital, Chiayi, Chiayi, Taiwan, 3Department of Medical Oncology, Chang Gung Memorial Hospital-Kaohsiung, Kaohsiung, Taiwan, 4Department of Medical Oncology, Chang Gung Memorial Hospital, Keelung, Keelung, Taiwan, 5 Department of Medical Oncology, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan, 6Department of Surgery, Chang Gung Memorial HospitalLinkou, Taoyuan, Taiwan Background: Assessing the post-surgical risk of relapse in patients with major salivary gland carcinomas (MSGCs) is an important but difficult task because of the broad spectrum of histological tumor subtypes and diverse clinical behaviors. We aimed to develop and validate a nomogram, which would allow us to predict the probability of recurrence in patients with MSGCs. Methods: Two hundred and thirty-one patients who had undergone radical surgery for MSGC treatment between 2002 and 2014 from a specific medical center were used as a training set. Clinicopathological variables with the most significant values in the multivariate Cox regression analysis were used to build into a nomogram capable of estimating the 5-year recurrence probability. An independent validation set, composed of 139 patients treated during the same period in three other hospitals, were selected for external validation and calibration. Results: The 5-year recurrence rate was 23.2% for the training set and 21.4% for the validation set. The nomogram was developed based on six significant predictive factors of tumor recurrence retained in the multivariate Cox model, including smoking history, tumor grade, perineural invasion, lymphatic invasion, and pathological T- and Nclassifications. The nomogram had a highly predictive performance, with a bootstrapcorrected concordance index of 0.82 for the training set and 0.78 for the validation set. The nomogram showed good calibration in predicting 2-year and 5-year recurrence probability in both the training and validation set. Conclusions: We developed and externally validated an accurate nomogram to predict the tumor relapse probability in patients who had been surgically treated for MSGCs. This nomogram may be used to assist clinicians and patients in specifying the potential risk of relapse and thereby providing more information for the selection of appropriate adjuvant treatments. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 363PD Community based screening for early detection of head and neck cancer among tribal community in Wayanad District, India S. Palliyal DM Wayanad Institute of Medical Sciences, DM Wayanad Institute of Medical Sciences, Kalpetta, India Background: Head and neck cancer ranks in the top three of all cancers in India. Wayanad district in Kerala state is a region in which 17% of the population is represented by tribal groups. These tribes generally live under severe socioeconomically deprived conditions. Common risk factors include tobacco use, culturally determined practices, alcohol consumption, and nutrition deficits. Head and neck cancer, despite its high incidence and prevalence in the region, does not benefit from significant prioritization like other cancer entities. The objectives are to create awareness regarding common cancers among tribal community in Wayanad District, India; to detect pre-cancers of head and neck region by conducting screening with simple low-cost technology within the community; and to facilitate confirmation of diagnosis among screen positives and treatment and follow-up among the diagnosed cases. This is community based screening program for early detection of head and neck cancer being implemented among socio-economically disadvantaged tribal community in Wayanad District, India. Methods: The process involves selection of clusters, household surveys, health education and screening the tribes for common cancers by primary health care workers at temporarily set-up clinics within the community. Stratification was done according to age and in consistent with W.H.O pathfinder methodology.The program will cover 142320 disadvantaged people in one year. 11670 people have been covered to date. Results: The compliance for screening head and neck cavity are 86.70% and the screen positivity rates is 3.01% respectively. 78 head and neck pre-cancers have been diagnosed among the screened tribes and all of them have complied to treatment. The prevalence of precancerous lesion on head and neck region was found to be 41% among the population. doi:10.1093/annonc/mdw587 | ix113 abstracts It was observed that 23% had leukoplakia, 18% population suffered from oral submucous fibrosis(OSMF), and 12% of them were recorded with smokers palate in their oral cavity. Conclusions: Screening for head and neck cancer with simple, low cost, acceptable and effective technology is feasible at community level in developing countries and can assist detection of precancers and early stage cancers. Clinical trial indentification: DM WIMS2 Legal entity responsible for the study: Shanavas Palliyal Funding: DM Foundation Disclosure: All authors have declared no conflicts of interest. 364PD measures; both groups had acute toxicity but the toxicity in group B was very significantly induced. Mucusitis in group A was significantly (p < 0.000) better than in group B. In group A dermatitis and weight were better than group B. wBC and Cr in both groups were not different. Conclusions: It seems that the use of Cox-2 inhibitors may reduce toxicity, especially mucositis resulting from chemoradioation in head and neck cancer. Legal entity responsible for the study: Dr Mojahed Funding: Tehran University Medical School - Departman Radiation Oncology Disclosure: All authors have declared no conflicts of interest. 366P Head & neck cancer pharmacogenetics: case control study on 5- fluorouracil and cisplatin adjuvant treatment outcome S.S.Y. Bhatia1, D. Parmar2 Biosciences, Amity Institute of Biotechnology, Noida, India, 2Developmental Toxicology Division, IITR, Lucknow, India 1 Background: Pharmacogenetics is the study of variability in drug responses due to heredity. It attempts to identify specific genes that are associated with specific diseases and that may be targets for new drugs. Cytochrome P4502D6 (CYP2D6) is of great pharmacogenetic interest due to its involvement in the biotransformation of several anticancer compounds to the active metabolites. And therefore, variations in the activity of CYP2D6 enzyme due to genetic polymorphisms may alter activity directly affecting the concentrations of active metabolites. CYP2D6*4 (G1934A), located on intron 3 and exon 4 junction, and CYP2D6*10 allele (C100T at exon 1), results in decreased catalytic activity of the enzyme and may lead to inappropriate metabolism of the anticancer drug thus, leading to variation in treatment outcome. The present study was undertaken to investigate the association of variant genotypes of CYP2D6 with the treatment response (personalized medicine approach) in head & neck cancer cases receiving adjuvant 5-fluorouracil and cisplatin. Methods: 300 patients suffering from head & neck cancer and equal number of age matched controls were included in the study. Genomic DNA was isolated from the blood samples and CYP2D6 genotypes were determined in genomic DNA by PCR based RFLP. Follow-up carried out to correlate the association (if any) in between variants and treatment outcome. Chi-square test and logistic regression models were used to determine associations between genotype, use of concomitant CYP2D6 inhibitors and disease relapse rate. Results: The frequency of variant alleles of CYP2D6 (CYP2D6*4 & *10) was found to be significantly higher in the cases when compared with the controls. The variant genotypes have lower benefit of 5-fluorouracil and cisplatin adjuvant treatment and tend to have a higher risk of disease relapse. Conclusions: This study suggests that the presence of the inactive CYP2D6*4 & *10 causes a reduction in the metabolic activation of anticancer agents, thereby lowering the risk of toxicity but worsening the therapeutic response. Legal entity responsible for the study: Council for Scientific & Industrial Research Funding: Council for Scientific & Industrial Research Disclosure: All authors have declared no conflicts of interest. 365PD Annals of Oncology The role of Cox-2inhibitor in combination with chemoradiotherapy in head and neck carcinoma to reduce mucositis and other side effects H. Tahara1, Y. Nishiyama1, S. Okamoto1, S. Okano2, M. Tahara2 Hiroshima University Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan, 2Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan 1 Background: Screening for Head and Neck Cancer requires stable, easy to use, and sensitive biomarkers that show characteristic changes at an early stage and recurrent cancer. Recent studies have demonstrated that miRNAs stably exist in body fluids and their expression patterns in cancer patients are distinct from those in healthy individuals. In this study, we analyzed non-coding small RNAs including miRNAs that specifically exist in plasma of patients with tongue cancer as novel biomarkers. Methods: Plasma levels of miRNAs and other non-coding small RNAs in patients with tongue cancer (n ¼ 24) vs healthy individuals (n ¼ 24) and in patients preoperative (n ¼ 24) vs postoperative (n ¼ 24) were performed by using NGS (Ion PGM, Life Technologies) . The data analysis was performed using software (GMP Genomics), and identified sequences that distinguished between tongue cancer and normal healthy individuals. Validation experiments are performed with real-time PCR. In further analysis, levels of expression were compared between with (n ¼ 5) and without recurrence individuals (n ¼ 12). Results: Twenty circulating miRNAs and isomiRs (few nucleotide lacks and/or additions compared with mature miRNA sequences) that more or less in patient plasma compared with control (jFold Changej>2.0, P < 0.05) were identified. Four combination levels of two miRNAs made significant discrimination between patients and healthy individuals better than one (AUC >0.97). Those combinations of miRNAs demonstrated positive detection at stage I. The ratio (postoperative/preoperative) of a combination of microRNAs demonstrated promising difference between with and without recurrence individuals (p ¼ 0.06, AUC¼0.8) for prediction of recurrence. Conclusions: We demonstrated four combinations of circulating miRNAs potentially useful for detection of early-stage head and neck cancer, and another combination that is worth characterizing as a predictor of postoperative recurrence. Legal entity responsible for the study: Hiroshima university Funding: The Japan Agency for Medical Research and Development (AMED) Disclosure: H. Tahara: Stockfolder in MiRTeL.Co.Ltd. S. Okano: Merck Serono Co., Ltd. (lecture fee). M. Tahara: Merck Sharp & Dome, Pfizer, Astra Zeneca (advisory board, research funding), Bayer (advisory board, lecture honorarium), Eisai (lecture honorarium, research funding), Otsuka, Boehringer Ingelheim (lecture honorarium), Novartis (research funding). All other authors have declared no conflicts of interest. 367P M.M. Mojahed Radiotherapy Oncology Valiasr, Qom University, Qom, Iran Background: Chemotherapy and radiotherapy-induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay or interruption of treatment plan, as well as reduce theraeutic index. Cyclo-oxygenase 2 (Cox2) is an inducible enzyme primarily expressd in inflamed tissue and tumor. Cox-2 inhibitors have shown promise as radio- and chemosensitizer and reduce radio induced toxicities. We conducted a phase III, randomised, double blind, clinical trial to evaluate the toxicity and efficacy of celecoxib, a selective Cox-2 inhibitor, administered concurrently with chemotherapy, and radiation for locally advanced head and neck. Here we report the first report about the role of Cox-2 inhibitor in acute toxicities. Methods: Patients with stage III/IV (locally advance) carcinoma of oropharynx, oral cavity, hypopharynx, larynx or nasopharynx who were referred to the department of radiation oncology were eligible. The end points of this study were acute toxicity, response rate and local control. Patients were treated with chemotherapy and concurrent radiation 60-70GY. Celecoxib (100 mg qid) was started on the first day of radiotherapy and was given for a total of 8 weeks. Acute toxicities were evaluated every week by WHO scale. Results: 122 patients were recruited to this study (each group with 62 patients), 74 male and 48 female with median age of 55.7 years. We used analysis of variance of repeated ix114 | abstracts Circulating microRNAs as novel promising biomarkers for early detection of tongue cancer Persistent elevation of plasma interleukin-8 or interferon-c after curative chemoradiotherapy predict early tumor recurrence and poor survival outcomes in patients with head and neck squamous cell carcinoma Y-L. Lin1, J.L-Y. Chen2, Y-S. Huang3 Medical Research, National Taiwan University Hospital, Taipei, Taiwan, 2 Oncology, National Taiwan University Hospital, Taipei, Taiwan, 3Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan 1 Background: To evaluate the prognostic significance of plasma proinflammatory cytokines in patients with head and neck squamous cell carcinoma undergoing curative chemoradiotherapy. Methods: This prospective study was approved by the IRB of our institute (201406075RINC). Head and neck squamous cell carcinoma non-metastatic patients receiving curative chemoradiotherapy were prospectively enrolled. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IFNc, and tumor necrosis factor-a] were evaluated at two time points (before chemoradiotherapy, and 2 weeks after completion of chemoradiotherapy). Associations of the plasma level of cytokines and clinical outcomes were evaluated. Volume 27 | Supplement 9 | December 2016 abstracts Annals of Oncology Results: Thirty patients were included. The primary sites of cancer were oropharynx (33%), oral cavity (23%), hypopharynx (23%), larynx (10%), and others (10%). Most patients had stage IV disease. The median radiotherapy dose was 70 Gy in 33 fractions. With a median relative short follow-up of 15.9 months, early tumor recurrence was noted in twelve 12 patients (40%), and death was noted in 6 patients (20%). Among the 8 proinflammatory plasma cytokines, IL-8 and IFN-c were significantly associated with survival outcomes. The mean IL-8 levels before and after treatment were 1.6 and 4.1 pg/ mL, respectively. The mean IFN-c level before and after treatment were 4.7 and 2.8 pg/ mL, respectively. In univariate analysis, stage IV (p ¼ 0.047), persistent elevation (level after treatment was greater than or equal to the level before treatment) of plasma IL-8 (p ¼ 0.024) or IFN-c (p ¼ 0.006) were significantly associated with early tumor recurrence and poor overall survival. In multivariate analysis, patients with persistent elevation of plasma IL-8 or IFN-c, independent of stage, had significantly worse RFS (HR 3.0, p ¼ 0.038 for persistent elevation of plasma IL-8; HR 8.8, p ¼ 0.026 for IFN-c). Conclusions: In patients with head and neck squamous cell carcinoma undergoing curative chemoradiotherapy, persistent elevation of plasma IL-8 or interferon-c after treatment may predict early tumor recurrence and poor overall survival. Legal entity responsible for the study: National Taiwan University Hospital Funding: National Taiwan University Hospital Disclosure: All authors have declared no conflicts of interest. 368P Influence of pre-RT haemoglobin levels on mucositis in locally advanced head and neck squamous cell carcinoma treated with concurrent chemo radiation K. Perumal1, R.K. Narayanasamy2, M. Sekhar2, S. Thyagarajan2, B. Ramakrishnan3 1 Radiation Oncology, Apollo Speciality Hospital, Chennai, India, 2Radiotherapy, Rai CBCC Cancer Center, Chennai, India, 3Biostatistics, Apollo Speciality Hospital, Chennai, India Background: Oral mucositis is one of common complication during chemoradiation of locally advanced head and neck squamous cell carcinoma (HNSCC). We prospectively analysed the role anaemia in patients having mucositis and is severity. Methods: 120 HNSCC (T3-T4a, N1-N2c) patients undergoing chemoradiation were prospectively evaluated for influence of Pre-RT haemoglobin on mucositis. All patients were in locally advanced disease stage III –IV. Sub-sites included were oral cavity, ororphaynyx, hypopharynx & laynyx. All patients received weekly inj.Cisplatin 40 mg/ m2) along with radiation to a total dose of 66Gy to PTV. All patients were evaluated weekly by clinical examination for grade of mucositis and hemogram. Results: Our population was characterized by a mean age of 55610.7 years (range: 2769), 85 were males and 35 females with a performance status of ECOG 1-2. The mean pre-RT haemoglobin was calculated (using ROC) as 10.3 g/dl. Among 120 patients 56 had grade 2 mucositis (48 were >10.3g/dl and only 8 were < ¼10.3g/dl); 64 patients had grade 3 mucositis (17 were >10.3g/dl and 47 were < ¼10.3g/dl)(p value <0.005). Conclusions: Lower pre-RT haemoglobin level of < ¼ 10.3 g/dl is statistically significantly associated with higher grade mucositis (grade 3). Legal entity responsible for the study: N/A Funding: Rai CBCC Center Disclosure: All authors have declared no conflicts of interest. 369P (46.25%) patients, T2N2M0 in 5 (6.25%), T3N1M0 in 26 (32.5%), T3N2M0 in 12 (15%) patients. The mean dose of radiation at the time of occurrence of mucositis was 21 Gy (without glutamine) vs. 29 Gy (with glutamine); dysphagia was 22 Gy (without glutamine) vs. 24 Gy (with glutamine); of skin reactions was 21 Gy (without glutamine) vs. 24.25 Gy (with glutamine); 7.5% had treatment breaks (with glutamine) with a range of 2-5 days vs. 32.5% (without glutamine) with a range of 3-10 days (p < 0.001). The mean maximum grade of oral mucositis glutamine arm vs. placebo was 2 vs. 2.27 (p ¼ 0.0001); dysphagia was 2.05 vs. 2.32(p ¼ 0.002); skin reactions was 2.07 vs. 2.2 (p ¼ 0.105); grade 3 skin reactions 7.5% vs. 20% respectively. Conclusions: Glutamine supplementation in HNSCC delays the onset of mucositis, skin reactions, dysphagia and decrease the treatment breaks. Legal entity responsible for the study: N/A Funding: Apollo Specialty Hospital. Disclosure: All authors have declared no conflicts of interest. 370P G.S. Sarode, S.C. Sarode Oral Pathology and Microbiology, Dr. D. Y. Patil Dental College and Hospital, Pimpri, Pune, India Background: Oral squamous cell carcinoma (OSCC) is an aggressive epithelial malignancy with around 270,000 new cases occurring annually. Diagnostic delay is a significant factor in disease progression. The time between diagnosis of oral potentially malignant disorder (OPMD) and malignant transformation is relatively short. Moreover, high-risk group individuals require repeated screening at regular intervals. Bioimpedance has emerged as a better screening tool over the current methods. Clinically and histopathologically relevant information about OSCC and OPMDs can be found in multi-frequency impedance spectra. At present, no studies using bioimpedance for the detection of OPMDs have been reported in the literature till date. Methods: Four electrical properties for each OPMD were measured: impedance; phase angle; real part of impedance; and imaginary part of impedance using an impedance analyzer at six different frequencies with applied voltage of 200 mV. Results: a. In leukoplakia, impedance values were seen to decrease from stage I to stage IV. Statistically significant differences in values of impedance were observed between all the stages of leukoplakia at 20Hz and 50kHz frequency. Impedance values declined as the histological grade progressed from no dysplasia to severe dysplasia. b. In erythroplakia, bioimpedance values declined as the histological grade progressed from no dysplasia to severe dysplasia. Statistically significant differences were also observed between all the grades of dysplasia at frequencies of 20Hz and 50kHz. c. In OSMF, impedance values declined as the histological grade progressed from mild to severe dysplasia. Statistically significant differences in values of impedance were also observed between all the grades at 20Hz and 50Hz. d. A statistical significant difference amongst all the parameters of different study groups was found at almost all the frequencies. Conclusions: Bioimpedance can be developed as a routine diagnostic decision support tool that can assist the classical visual screening in screening programs, in primary care centers or in developing countries where the organizational structure and economical factors limit national screening programs. Legal entity responsible for the study: N/A Funding: The study was carried out in Dr. D. Y. Patil Dental College and Hospital Disclosure: All authors have declared no conflicts of interest. Impact of glutamine supplements in altering the toxicity profile in head and neck cancer patients receiving concurrent chemoradiotherapy K. Perumal, P.K. Reddy, M. Potharaju Radiation Oncology, Apollo Speciality Hospital, Chennai, India Determination of bioimpedance in oral potentially malignant disorders 371P Effect of oral silymarin administration on prevention of radiotherapy induced mucositis: A randomized, doubleblinded, placebo-controlled clinical trial S. Hosseini1, S. Elyasi2, M.R. Niazi Moghadam3, S.A. Aledavood1, G. Karimi4 Clinical oncology, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, Mashhad, Iran, 2Clinical Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran, 3Department of Clinical Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran, 4Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 1 Background: To compare the toxicity profile and treatment breaks during concurrent chemo radiation with or without glutamine supplements in non-metastatic head and neck squamous cell carcinoma (HNSCC). Methods: This prospective non randomized double arm observational study involved the assessment and comparison of toxicity profile in 80 HNSCC patients treated by 3DConformal Radiotherapy with concurrent weekly cisplatin (40mg/m2). Glutamine was administered as 10 grams of L-Glutamine mixed with 200 ml of water two times a day. All the patients were reviewed weekly for toxicity assessment and graded using RTOG Acute Radiation Morbidity Grading System. 40 (50%) received glutamine supplements. Results: Our patient population was characterized by 64 males (80%) and 16 females (20%) with a mean age of 54 years (range 13-74 years) with site wise distribution of carcinoma hypopharynx in 21 (26.25%) patients, carcinoma larynx in 24 (30%), carcinoma oral cavity in 22 (27.5%), carcinoma oropharynx in 10 (12.5%), and carcinoma parotid in 3 (3.75%) patients and stage wise distribution of T2N1M0 in 37 Volume 27 | Supplement 9 | December 2016 Background: Mucositis is a frequent severe complication of radiation therapy in patients with head and neck cancer. Silymarin is a polyphenolic flavonoid extracted from the milk thistle that exhibits a strong antioxidant and anti-inflammatory activities. In this study, we evaluated silymarin efficacy in prevention of radiotherapy-induced mucositis in patients with head and neck cancer as the first in human study. Methods: During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting at the first day of radiotherapy session and continuing for six weeks on oral mucositis occurrence doi:10.1093/annonc/mdw587 | ix115 abstracts were assessed. Twenty-seven patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization (WHO) and National Cancer Institute-Common Terminology Criteria (NCI-CTC) oral mucositis grading scale scores were recorded at baseline and weekly during the 6 weeks. Results: The median WHO and NCI-CTC scores was significantly lower in the silymarin group at the end of the first to sixth week (P < 0.05). The scores increased significantly in both placebo and silymarin groups during radiotherapy but there was a delay for mucositis development and progression in the silymarin group. Conclusions: Prophylactic administration of conventional form of silymarin tablets could reduce radiotherapy-induced mucositis in patients with head and neck cancer. Legal entity responsible for the study: N/A Funding: Research Council of Mashhad University of Medical Sciences and to Goldaroo Company Disclosure: All authors have declared no conflicts of interest. 372P Determination of expression of EGFR in premalignant and malignant lesions of the oral cavity and evaluating the role of Gefitinib in EGFR positive lesions U. Velu Radiation Oncology, All India Institute of Medical Sciences, Delhi, India Background: Determination of expression of EGFR in premalignant and malignant lesions of the oral cavity and evaluating the role of Gefitinib in the same Methods: 130 Patients with premalignant and malignant lesions of oral cavity from JK cancer institute, Kanpur were selected. EGFR status evaluation was done in all the patients. Premalignant lesions over expressing EGFR were observed for transformation into malignant lesions and were given Tab Gefitinib 250 mg OD daily. Malignant lesions with over expression of EGFR were randomly divided into 2 groups first group consisted of patients who were given CCRT(cisplatin). The other group had the same regimen but with the addition of Tab Gefitinib 250 mg daily Results: Out of 130 patients registered 53 were premalignant out of which EGFR(þ) positive in 73% (39) patients. EGFR ( þþ)over expression were in 8%(4)patients, EGFR negative in 18%(10) patients. 77 were malignant lesions EGFR positive in 89%(51) patients. EGFR(þ)in 38%(27) of patients, EGFR( þþ)in 40% (28) patients, EGFR( þþþ) were expressed by 11% (11) patients. EGFR negative in 11%(11 patients) 30patients(total 34) in CCRTþ gefitinib arm have shown complete response in comparison to 20patients(total 32) in CCRT arm Conclusions: EGFR status evaluation in premalignant can be used as a screening tool for detection of transformation into malignant lesions. We can prevent this transformation by EGFR inhibitors. In malignant lesions it can be really important for the role of EGFR inhibitors .Eg Gefitinib has shown good results when combined with the conventional CCRT. Legal entity responsible for the study: JK Cancer Institute, Kanpur Funding: JK Cancer Institute Disclosure: All authors have declared no conflicts of interest. 373P Synchronous or metachronous esophageal cancer is associated with a lower survival rate in patients with head and neck squamous cell carcinoma H.M. Kim1, J.H. Lee1, S.J. Baek2 Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea, 2Head and Neck Surgery, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea 1 Background: It is well known that patients with head and neck squamous cell carcinoma (SCC) have a high incidence of synchronous or metachronsous esophageal SCC. This study attempted to investigate an effect of esophageal cancer on the survival of patients with head and neck cancer (HNC). Methods: Of patients with HNC, those with pathologically-proven SCC were enrolled in Wonju Severance Christian Hospital, Wonju, Korea. All patients received esophagogastroduodenoscopy at the time of HNC diagnosis and at regular interval. Survival times were calculated by Kaplan-Meier analysis and compared by log rank test. Results: Between 2000 July and 2013 June, a total of 218 patients with HN SCC were analyzed with 202 men (92.7%) and a mean age of 64.3 6 11.0. Esophageal SCC was diagnosed in 15 patients (6.5%) with a mean age of 61.7 6 9.4 years and gastric neoplasm including tubular adenoma and adenocarcinoma was diagnosed in 13 patients (5.6%) with 66.2 6 7.9 years, and both cancers were diagnosed in 1 patient (0.4%). The rate of synchronous and metachronous esophageal SCC was 6 (40%):9 (60%). The median follow-up time was 29.8 moths (0-149.4). The estimated survival times were 74.6 (95% CI: 65.3-83.9) of HNC without EC and 38.1 (95% CI 20.2-56.1) of HNC with EC (P ¼ 0.042). ix116 | abstracts Annals of Oncology Table: 373P Characteristics Esophagus Stomach Both n Age Sex (M:F) Pathology Squamous cell carcinoma Tubular adenocarcinoma Tubular adenoma Site Upper Middle Lower Unknown 15 61.7 6 9.4 14:1 13 66.2 6 7.9 13:0 1 69 1:0 15 (100%) 0 0 0 9 5 1 1 0 2 (13.3%) 8 (53.3%) 5 (33.3%) 0 0 7 (53.8%) 5 (38.5%) 1 (7.7%) E S Conclusions: Esophageal SCC had a negative effect on a survival of patients with head and neck SCC. Legal entity responsible for the study: Hee Man Kim Funding: Yonsei University Wonju College of Medicine Disclosure: All authors have declared no conflicts of interest. 374P Trends in incidence of head and neck cancers in India C.J.K. Francis Social Work, Nestle India Limited, Gurgaon, India Background: India is classified as a lower-middle-income group country by the World Bank. Head and neck cancers are among the 10 most common cancers globallyand are the most common cancers in developing countries, especially in Southeast Asia. In India, it accounts for one fourth of male cancers and one tenth of female cancers. This is mainly attributed to tobacco, areca nut, alcohol, etc. Oral cancers are most common amongst all head and neck squamous cell cancers (HNSCC). HNSCC in the developing world differ from those in the Western world in terms of age, site of disease, etiology, and molecular biology. Poverty, illiteracy, advanced stage at presentation, lack of access to health care, and poor treatment infrastructure pose a major challenge in management of these cancers. The Cancer Atlas project by the Indian Council for Medical Research (ICMR) has shown the incidences of various cancers in different parts of India. Ninety percent of the oral cancer patients in rural areas belong to the lower or lower-middle socio-economic class, and 3.6% are below the poverty line. Methods: Objectives 1. To determine the trends in incidence of head and neck squamous cell carcinoma over a time period in India. 2. To compare change in the trends of head and neck squamous cell carcinoma of India and developed countries. Materials & Methods The tumor registry data was taken from South Indian cancer registry (Chennai-1986-98) and from a rural (Kancheepuram - 1988-98) registry, which has data for a long period since 1982 and 1987 respectively to identify the change in trends of head and neck cancers. Chennai, a South Indian urban cancer registry caters to an area of 170sq.km and a population of 4.2 millions. The National Cancer Registry Programme of the Indian Council of Medical Research(ICMR) monitors these cancer registry data. The data from these two registries were usedtoanalyze change in trends within the country. Results: Incidence rate is higher in more developed countries than less developed countries. Male preponderance is forthcoming. .The overall male: female ratio of head and neck cancers in urban population is 2:1and inrural population is 5:1. Conclusions: A trend is emerging showing that the type of oral cancers that patients present with arechanging, with a definite increase in the number of patients presenting with tonguecancer. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest. 375P Prevalence of head and neck cancers and tobacco use among Malayali tribes, Yelagiri Hills, Tamil nadu, India D.L. Francis Public Health Dentistry, Tamil Nadu Dr MGR Medical University, Chennai, India Background: India has the second largest tribal population of the world next to the African countries. Despite remarkable world-wide progress in the field of diagnostic, curative and preventive medicine, still there are large populations of people living in Volume 27 | Supplement 9 | December 2016 abstrac
