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 Ablative Treatments: Cryo HIFU Laser Microwave : less invasive? 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 Brain Tumors Testicular Ca Adv. Lung Ca Rectal Ca Sarcomas Adv. Cervical Ca Endometrial Ca Pediatric Ca Adv. Head & Neck Ca Bladder Ca Metastatic disease: Bone / Brain / Other
Improving RT Delivery 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 Impact Explore new indications Treat deeper tumors Decrease skin toxicity Treat smaller areas Individualization Decrease toxicity in deeper organs Increase in tumor doses Improve tumor control Higher daily doses Faster, Better, Safer treatments
Improving RT Techniques and Outcomes 1995-2000 Beam shaping devices: MLCs 2000-2005 In-room image guidance 2005-2010 Partially integrated systems Novelty IMRT IGRT Dedicated devices Clinical Impact Head/Neck: improve saliva / swallowing Pelvis: Less bowel toxicity Allows safer chemotherapy administration Prostate Ca: Enable dose escalation: improve cure Reduce traditional set-up errors Multivendor environment Increased complexity Decrease throughput Increase safety concerns. 2010-2015 Hypofractionation, Adaptive RT SRS SBRT/SABR ART Lung Ca SBRT: improve cure Frameless CNS radiosurgery Partial breast accelerated irradiation 2015-Future Integration of Better Beam Shaping and Aiming Need for increased integration and/or interoperability Faster, better, safer treatments Global RT: 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 RapidPlan Manual Rapid Plan Time 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) 57 th Annual Meeting & Exhibition; July 12-16, 2015; Anaheim, CA. University of Michigan
KNOWLEDGE-GUIDED ONCOLOGY: Royal Surrey County Hospital: Prostate Study 350 Planning time (min) Manual RapidPlan Time 114 ± 86 min 21 ± 13 min Equivalent or better 30% 90% Better 10% 90% Courtesy, Royal Surrey County Hospital NHS Foundation, Guilford, UK Data source on file 300 250 200 150 100 50 0 A1A2A3A4B1B2C1D1D2D3E1E2E3F1F2F3F4F5F6 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 VMAT 4 π HDRT Works in Progress Dong P et al. IJROBP 86(3):407-13, 2013
INTELLIGENT TREATMENT DELIVERY: High Definition Radiosurgery Brain Stem Brain Stem 50% Rx Dose 50% Rx Dose Coplanar RapidArc SRS 4π High Definition SRS Works in Progress
Promise of Protons
ADVANCED DATA ANALYTICS: InSightive Analytics Operational Efficiencies Referral Patterns Clinical Outcome Analysis ADVANCED DATA ANALYTICS
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 Cardiac Arrhythmia (Atrial Fibrillation) Works in Progress
Cardiac Arrhythmias: A New RT Frontier?
Short course Intermediate Long course Colectomy Cystectomy Lobectomy Pancreatectomy Office Hospital Affordable, Accessible, Quality Care Cost of Cancer Care in US 30% increase from 2010 to 2020 $120,000 $100,000 Average Cost per Patient Average cost for one extra year of life: 1995: $54,100 2005: $139,100 2013: $207,000 $80,000 $60,000 $40,000 $20,000 $0 RT Surgery Chemo (1 year) Sources: Avalere study, 2015 National Bureau of Economic Research
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 The Key To Progress: Better Dose Delivery $10M MR LINAC $3-4M? 3D CONFORMAL IMRT IGRT SBRT HDRT