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Future of Radiation Therapy JP Morgan Healthcare Conference January 12, 2016 Deepak Khuntia, MD, VP of Medical Affairs Patrick Kupelian, MD, VP of Clinical Affairs Cancer as a cause of death CANCER TREATMENT MODALITY: RADIOTHERAPY Localized Treatments: Surgery : less invasive? Ablative Treatments: Cryo HIFU Laser Microwave Systemic Treatments: Drugs: Traditional ChemoRx Hormonal Therapy Targeted Drugs Very few curative therapies Minor improvements in subsets of patients Radiation Therapy (RT): Spectrum of biologic effects • Ablative: SRS/SBRT •Biologic therapy Organ-sparing DNA changes Immune modulation DISEASES TREATED WITH RT Curable Cancers with RT ALONE: Prostate Ca Head & Neck Ca Lung Ca Cervical Ca Skin Ca Curable Cancers with RT as part of treatment (adjuvant): Breast Ca Adv. Lung Ca Adv. Cervical Ca Adv. Head & Neck Ca Brain Tumors Rectal Ca Endometrial Ca Bladder Ca Metastatic disease: Bone / Brain / Other… Testicular Ca Sarcomas Pediatric Ca Improving RT Delivery Impact Aim: Increase Cure / Decrease Toxicity Process: Improve RT Shaping and Targeting 1950-60s 1970-80s 1990s 2000s 2010s Cobalt Early Linacs Higher Energy Linacs Beam Shaping Devices In-room Image Guidance Integration of Better Beam Shaping and Aiming • Treat deeper tumors • Treat smaller areas • Individualization • Increase in tumor doses • Higher daily doses • Decrease skin toxicity • Decrease toxicity in deeper organs • Improve tumor control • Faster, Better, Safer treatments Explore new indications Improving RT Techniques and Outcomes Novelty Clinical Impact 1995-2000 2000-2005 2005-2010 2010-2015 2015-Future Beam shaping devices: MLCs In-room image guidance Partially integrated systems Hypofractionation, Adaptive RT Integration of Better Beam Shaping and Aiming IMRT • Head/Neck: improve saliva / swallowing • Pelvis: Less bowel toxicity • Allows safer chemotherapy administration IGRT • Prostate Ca: Enable dose escalation: improve cure • Reduce traditional set-up errors • Dedicated devices • SRS • Multivendor environment • SBRT/SABR • Increased complexity • Lung Ca SBRT: improve cure • Faster, better, safer treatments • Decrease throughput • Frameless CNS radiosurgery • Global RT: • Increase safety concerns. • Partial breast accelerated irradiation Need for increased integration and/or interoperability • ART • Simpler set-ups • Education & training Brain Mets Study: Adding SRS Improves Survival Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May 22;363(9422):1665-72. RapidArc Radiosurgery: Treating 11 Melanoma Mets Treatment Details • 18 Gy x 1 • 4 non-coplanar arcs • 1-360, 3-170 • 18 min treatment • 5 min beam-on • 708 control points Lung Cancer: Patients live longer with Radiosurgery than with Surgery SBRT vs. Lobectomy for Operable Stage I NSCLC Source: Chang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol. 2015 Jun;16(6):630-7. PROSTATE CANCER IMAGE GUIDANCE: IMPROVING CURE AND REDUCING TOXICITY Cancer Control Rates Toxicity Rates Memorial Sloan Kettering Cancer Center Prostate Cancer RT: Outcome with and without Image Guidance Zelefsky, IJROBP, 84, 125-129, 2012 Shaping of Radiation Lowers Complications Conventional RT IMRT Reduce Bowel Complications Cancers impacted: Prostate Ca Rectal Ca Anal Ca Cervical Ca Reduce Head & Neck Complications Complications reduced: Less dryness of the mouth Less swallowing problems Less scarring of joints / muscles Chopra et al. ASTRO Plenary, San Antonio October 2015. Gupta et al. Radiotherapy and Oncology. 104:3 (343-348), 2012. IMAGE – Not Yet Complete New Era Innovation Knowledge-Guided Oncology | Intelligent Treatment Delivery Advanced Data Analytics KNOWLEDGE-GUIDED ONCOLOGY: RapidPlan™ Ramp Up 300+ Orders 3,800 Potential Installs Disease Site Models Prostate Prostate (+lymph nodes) Head & Neck Lung SBRT Breast More Models Coming KNOWLEDGE-GUIDED ONCOLOGY: University of Michigan: Spine SBRT Study Manual Time Manual Rapid Plan 60-90 min 15-20 min Equivalent Quality Foy J, et al. An analysis of knowledge based planning for stereotactic body radiation therapy of the spine [abstract]. Poster presentation at: American Association of Physicists in Medicine (AAPM) 57th Annual Meeting & Exhibition; July 12-16, 2015; Anaheim, CA. University of Michigan RapidPlan KNOWLEDGE-GUIDED ONCOLOGY: Royal Surrey County Hospital: Prostate Study 350 Manual Time Equivalent or better RapidPlan™ 114 ± 86 min 21 ± 13 min 30% 90% Planning time (min) 300 250 200 150 100 Better 10% 90% 50 0 Courtesy, Royal Surrey County Hospital NHS Foundation, Guilford, UK Data source on file A1A2A3A4B1B2C1D1D2D3E1E2E3F1 F2 F3 F4 F5 F6 conventional RapidPlan INTELLIGENT TREATMENT DELIVERY: High Definition Radiotherapy (HDRT) Works in Progress INTELLIGENT TREATMENT DELIVERY: 4π Dose Compression for Lung SBRT 64 Gy PATIENT 1 PATIENT 2 15 Gy IMRT Works in Progress VMAT Dong P et al. IJROBP 86(3):407-13, 2013 4 π HDRT INTELLIGENT TREATMENT DELIVERY: High Definition Radiosurgery Brain Stem Brain Stem 50% Rx Dose Coplanar RapidArc SRS Works in Progress 50% Rx Dose 4π High Definition SRS Promise of Protons ADVANCED DATA ANALYTICS: InSightive™ Analytics ADVANCED DATA ANALYTICS Operational Efficiencies Referral Patterns Clinical Outcome Analysis ADVANCED DATA ANALYTICS: Velocity TM Creates the cancer story from imaging Imaging informatics integrated with our Big Data Analytics Improve outcomes, quality, and efficiency Radio-immunotherapy for Cancer Treatment Hodge, Guha, Neefjes, Gulley. Oncology, 2008 August, 22(9):1064-1084 Abscopal Responses in Metastatic Non-Small Cell Lung Cancer (NSCLC) Patients Treated on a Phase 2 Study of Combined Radiation Therapy and Ipilimumab: Evidence for the In Situ Vaccination Hypothesis of Radiation E.B. Golden, A. Chachoua, M.B. Fenton-Kerimian, S. Demaria, and S.C. Formenti New York University ASTRO Annual Meeting October 2016 The Abscopal Effect: Radiotherapy in one site can potentially eradicate tumors elsewhere in the body • Combining radiosurgery with immunotherapy • Study of NSCLC • Study shows that SBRT with ipilumimab could increase tumor control and survival • 25% remission; 100% control/no progression Golden et al. ASTRO 2016. Targeted Therapies and Immunotherapies: Trend is in Combining Drugs Challenges of drug+drug combinations • Clinical trial design • Cost • Commercialization RT as a combination “drug” • Available • Cost-effective • Reimbursed 4. Radiation Medicine NEW FRONTIERS IN RADIATION ONCOLOGY Research opportunities in radiation medicine: Cardiac arrhythmias Emphysema Post-thoracic surgery neuropathy Plantar fasciitis Depression Arthritis Works in Progress Cardiac Arrhythmia (Atrial Fibrillation) Cardiac Arrhythmias: A New RT Frontier? Affordable, Accessible, Quality Care Cost of Cancer Care in US 30% increase from 2010 to 2020 Average Cost per Patient $120,000 $100,000 $60,000 $40,000 $20,000 RT Sources: Avalere study, 2015 National Bureau of Economic Research Surgery Hospital Office Pancreatectomy Lobectomy Cystectomy Colectomy Long course $0 Short course 1995: $54,100 2005: $139,100 2013: $207,000 $80,000 Intermediate Average cost for one extra year of life: Chemo (1 year) Technology Decreasing Treatment Cost: SBRT / SRS Technology (SBRT) Decreasing Actual Treatment Cost Time-driven activity-based costing (TDABC), UCLA SBRT Utilizing time-driven activity based costing to understand the short- and long-term costs of treating localized, low-risk prostate cancer. Laviana et al. Cancer. 2015 Conclusion • Advanced technology is increasing cure rates and lowering toxicity • Advanced technology will improve affordability, accessibility, and quality of radiotherapy • Radiation therapy utilization could dramatically increase with new opportunities outside of cancer Thank You INTELLIGENT TREATMENT DELIVERY: Relative Clinical Value $10M The Key To Progress: Better Dose Delivery $3-4M? MR LINAC 3D CONFORMAL IMRT IGRT SBRT HDRT