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Update on Ovarian Cancer Robert E. Bristow, MD, MBA Professor and Director Division of Gynecologic Oncology University of California, Irvine – Medical Center Ovarian Cancer Center Mission: •To provide exemplary and holistic clinical care to patients with ovarian cancer. •To enhance community awareness of ovarian cancer regarding the importance of early diagnosis and the benefits of centralized expert care. •To advance the science of the prevention and treatment of ovarian cancer in a meaningful way. Discover ▪ Teach ▪ Heal Gynecologic Oncology Faculty Discover ▪ Teach ▪ Heal Ovarian Cancer Center • Clinical Services - coordination of multidisciplinary care - prevention, early detection, cancer survivorship - surgery and regional therapeutics - chemotherapy and clinical trials - ancillary services • Community Outreach and Education - web-based platform - virtual support group survivor network - conferences - international visiting scholar program • Research and Discovery - molecular biology and translational science - healthcare outcomes Discover ▪ Teach ▪ Heal Ann’s Clinic Screening, Early Detection, Cancer Survivorship High-risk patients - genetic counseling & testing - surveillance programs - cancer prophylaxis Cancer survivors - programmatic plan - psycho-social wellness - management of treatment toxicities Discover ▪ Teach ▪ Heal Peritoneal Surface Malignancies Disease confined to peritoneal cavity for much of natural history Generally amenable to surgical resection Positive survival impact of chemotherapy - varies by disease site Discover ▪ Teach ▪ Heal Radical Surgery for Ovarian Cancer Uterus Bladder Tumor Right Ovary Sigmoid Tumor Left Ovary Discover ▪ Teach ▪ Heal Radical Surgery for Ovarian Cancer Uterus Bladder Tumor Distal Sigmoid Cervix Culdesac Tumor Discover ▪ Teach ▪ Heal Radical Surgery for Ovarian Cancer Vaginal Cuff Rectosigmoid Colon Discover ▪ Teach ▪ Heal Development of Intra-Peritoneal (IP) Chemotherapy • 1950’s: First use of intraperitoneal chemotherapy for malignant ascites • 1968: Long-term peritoneal access device • 1978: Demonstration of slow peritoneal clearance of some drugs • 1984: Feasibility of intermittent large volume intraperitoneal therapy • 1996: First report of a survival benefit for IP vs. IV chemotherapy in advanced ovarian cancer Discover ▪ Teach ▪ Heal Armstrong DK et al. NEJM 2006; 354:34. Discover ▪ Teach ▪ Heal PFS: 18.3 vs 23.8 months OS: 49.7 vs 66.9 months Armstrong DK et al. NEJM 2006; 354: 34. Discover ▪ Teach ▪ Heal The ‘Evolution’ of Treatment for Advanced Ovarian Cancer and Effect on Survival Surgical & Chemotherapy Improvements 66.9 57.4 80 52 (Optimal) (Optimal) Months 60 37 24 40 12 (Suboptimal) 14 20 0 1975 Alkeran 1983 1986 Cisplatin 1996 1998 Paclitaxel 2003 2006 IP Rx Discover ▪ Teach ▪ Heal Discover ▪ Teach ▪ Heal IP Therapy Discover ▪ Teach ▪ Heal IP Therapy Discover ▪ Teach ▪ Heal IP Therapy Discover ▪ Teach ▪ Heal IP Therapy Discover ▪ Teach ▪ Heal Primary Cytoreductive Surgery Contemporary Survival Outcomes Study Chemotherapy Residual Median Survival GOG152 IV-CDDP/IV-Taxol GOG172 IV-CDDP/IV-Taxol 0.1–1.0cm <1cm no gross 39 months 50 months 78 months IP-CDDP/IV+IP-Taxol 0.1–1.0cm <1cm no gross 53 months 67 months 127 months >1cm 36 months Rose PG et al. N Eng J Med 2004; 351: 2489. Armstrong DK et al. N Eng J Med 2006; 354: 34. Discover ▪ Teach ▪ Heal Hyperthermia and Neoplasia Heat is… Directly cytotoxic to cancer cells - disrupts microtubule system - induces primary protein damage - promotes vascular stasis Synergistic with some chemotherapy agents Knox 1991, Stellar 1998 Discover ▪ Teach ▪ Heal HIPEC Schematic Discover ▪ Teach ▪ Heal HIPEC Techniques Open (colisuem) Closed Discover ▪ Teach ▪ Heal Role of HIPEC in Ovarian Cancer Retrospective study design (1995-2005) Advanced ovarian cancer (n=43) Up-front HIPEC cisplatin + IV chemotherapy Morbidity – 13.9%; mortality – 2.3% Median OS = 53 months - complete initial resection = 131 months Median PFS = 39 months Melis A et al. Bull Cancer 2011, doi 21659062. Discover ▪ Teach ▪ Heal Burger RA et al. NEJM 2011; 365: 2473. Discover ▪ Teach ▪ Heal PFS: +3.8 month maintenance Rx OS: no significant effect Burger RA et al. NEJM 2011; 365: 2473. Discover ▪ Teach ▪ Heal Fertility Preservation • Ovarian cancer - conservative surgery - young patients - early stage disease, atypical tumor types - chemotherapy with ovarian suppression Discover ▪ Teach ▪ Heal Robotic Surgery ● daVinci surgical platform - patient-side robot - vision cart - robotic master console Advantages Improved visualization Finer instrument control and dexterity Ergonomic design Autonomous surgical environment Discover ▪ Teach ▪ Heal da Vinci® – Robotic Surgery Technology Discover ▪ Teach ▪ Heal Research and Discovery Clinical Trials • Ovarian cancer - intraperitoneal chemotherapy / HIPEC - molecular profiling - quality of life / cancer survivorship - developmental therapeutics / biologic agents Discover ▪ Teach ▪ Heal Research and Discovery QOH Ovarian Cancer Research Laboratory • PhD recruitment underway • Collaborative effort • Genetic screening and early detection • Molecular basis of disease - characteristics of long-term survivors - circumventing chemo-resistance Discover ▪ Teach ▪ Heal Research and Discovery • Surgical techniques • Advanced imaging techniques / onco-imaging • Clinical trials of new chemotherapeutic agents • Biological therapies • Public health applications Discover ▪ Teach ▪ Heal Research and Discovery Modern Approach to Cancer Therapeutics Pathways Analysis Patient Metabolism Genes Downregulated Mutations Genes Upregulated Discover ▪ Teach ▪ Heal OVA1 Qualitative serum test – 5 immunoassays - Apolipoprotein A - Transthyretin - 2 Microglobulin - Transferrin - CA125 II Single numerical result: 0 - 10 FDA approved September 2009 Ovarian mass, > 18y/o, planned surgery Triage tool for surgical decision-making Not a screening or independent diagnostic test Category Premenopausal Postmenopausal Low Risk <5.0 <4.4 High Risk ≥5.0 ≥4.4 Discover ▪ Teach ▪ Heal OVA1 Sensitivity vs CA125 Subjects OVA1 CA125-II All cancers (n=161) 92.5% 68.9% All epithelial ovarian cancers (n=96) 99.0% 82.3% Early stage EOC (n=41) 97.6% 65.9% Premenopausal women w/ early stage EOC (n=14) 92.9% 35.7% Overall Performance Performance Preoperative Assessment Assessment + OVA1 Sensitivity % 75 96 Specificity % 79 35 NPV % 87 95 PPV % 62 40 Ueland F. et al. Int Gyn Cancer Soc Annual Meeting, 2010, Prague. Discover ▪ Teach ▪ Heal Disparities in Epithelial Ovarian Cancer Quality of Care and Survival According to Race and Socioeconomic Status: a Study of 47,160 Patients from the National Cancer Data Base Robert E. Bristowa, Matthew A. Powellb, Noor Al-Hammadic, Ling Chenc, J. Phillip Millerc, Phillip Y. Rolandd, David G. Mutchb, William A. Clibye aDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology University of California, Irvine School of Medicine bDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology cDepartment of Biostatistics Washington University in St. Louis School of Medicine dGynecologic Oncology, Department of Gynecology and Obstetrics Saint Francis Francis Hospital and Medical Center eDivision of Gynecologic Surgery, Department of Obstetrics and Gynecology Mayo Clinic Discover ▪ Teach ▪ Heal Adherence to NCCN Guidelines Race 65.6% 61.5% 56.4% 51.3% 43.9% 35.6% * * * *p<0.0001 Discover ▪ Teach ▪ Heal Adherence to NCCN Guidelines Payer * * * *p<0.0001 Discover ▪ Teach ▪ Heal Adherent/Non-Adherent Care by Race 5-year Overall Survival N=47,160 Adherent White Non-adherent White Adherent African-American Non-adherent African-American p<0.0001 41.4% 37.8% 33.3% 22.5% Discover ▪ Teach ▪ Heal Outreach and Education Public Community - Education and Awareness - Virtual support network Resource for Professionals - Education and Awareness - Expedited referral system - Partnering in patient care Discover ▪ Teach ▪ Heal Thank you! Discover ▪ Teach ▪ Heal