Future of Radiation Therapy JP Morgan Healthcare Conference January - PowerPoint PPT Presentation

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? Radiation Therapy (RT): Ablative Treatments: Spectrum of biologic effects • Ablative : SRS/SBRT Cryo HIFU Laser Microwave Systemic Treatments: • Biologic therapy Drugs: Traditional ChemoRx Hormonal Therapy Organ-sparing Targeted Drugs DNA changes Immune modulation Very few curative therapies Minor improvements in subsets of patients

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 Higher Beam Shaping In-room Integration of Early Linacs Energy Devices Image Better Beam Linacs Guidance Shaping and Aiming • Treat deeper • Treat smaller areas • Increase in • Higher daily Explore new Impact indications tumors tumor doses doses • Individualization • Improve • Faster, Better, • Decrease toxicity in • Decrease tumor control Safer treatments deeper organs skin toxicity

Improving RT Techniques and Outcomes 1995-2000 2000-2005 2005-2010 2010-2015 2015-Future Beam shaping devices: In-room image Partially integrated Hypofractionation, Integration of Better MLCs guidance systems Adaptive RT Beam Shaping and Aiming • Dedicated devices • SRS Novelty IMRT IGRT Need for increased integration and/or • Multivendor • SBRT/SABR interoperability environment • ART • Head/Neck: improve • Prostate Ca: • Increased • Lung Ca SBRT: • Faster, better, safer Clinical Impact saliva / swallowing Enable dose complexity improve cure treatments escalation: improve • Pelvis: Less bowel • Decrease • Frameless CNS • Global RT: cure toxicity throughput radiosurgery • Simpler set-ups • Reduce traditional • Allows safer • Increase safety • Partial breast • Education & set-up errors chemotherapy concerns. accelerated training administration irradiation

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 Toxicity Rates Cancer Control 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 Planning time (min) 350 300 RapidPlan ™ Manual 250 114 ± 86 min 21 ± 13 min Time 200 Equivalent 150 30% 90% or better 100 10% 90% Better 50 0 A1A2A3A4B1B2C1D1D2D3E1E2E3F1F2F3F4F5F6 Courtesy, Royal Surrey County Hospital NHS Foundation, Guilford, UK conventional RapidPlan Data source on file

INTELLIGENT TREATMENT DELIVERY: High Definition Radiotherapy (HDRT) Works in Progress

INTELLIGENT TREATMENT DELIVERY: 4 π Dose Compression for Lung SBRT 64 Gy PATIENT 1 PATIENT 2 15 Gy 4 π HDRT IMRT VMAT Dong P et al. IJROBP 86(3):407-13, 2013 Works in Progress

INTELLIGENT TREATMENT DELIVERY: High Definition Radiosurgery Brain Stem Brain Stem 50% Rx Dose 50% Rx Dose 4 π High Definition SRS Coplanar RapidArc 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: TM Velocity  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  Cardiac Arrhythmia Arthritis (Atrial Fibrillation)  Works in Progress

Cardiac Arrhythmias: A New RT Frontier?

Affordable, Accessible, Quality Care Cost of Cancer Care in US Average Cost per Patient 30% increase from 2010 to 2020 $120,000 $100,000 $80,000 Average cost for one extra year of life: $60,000 1995: $54,100 $40,000 2005: $139,100 $20,000 2013: $207,000 $0 Short course Intermediate Long course Colectomy Cystectomy Lobectomy Pancreatectomy Hospital Office 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 $10M $3-4M? The Key To Progress: Better Dose MR LINAC Delivery 3D CONFORMAL IMRT IGRT SBRT HDRT