Best Practices in Identifying Proton-Appropriate Patients Presented by Dr. Ramesh Rengan Professor, Department of Radiation Oncology, University of Washington School of Medicine Medical Director, SCCA Proton Therapy Center Radiation Oncologist, University of Washington Medical Center Introduction

Protons are a form of radiation treatment that, for a subset of patients, may provide a clinical benefit when compared with standard radiotherapy.

2 Finding the 3%

Your challenge: Proton therapy is appropriate in only How can I make sure that 3-10% of solid tumor cases. my patient is But for that group, getting the best there are many expected treatment plan? clinical benefits.

3 Clinical Benefits of Proton Therapy

• Ability to apply higher therapeutic dosages, because the beam delivers the most radiation at the tumor site, reducing overall exposure • Expected reduction in radiation-caused secondary cancers - Particularly critical to young people and pediatric cases - Important to anyone with long life expectancy • Less radiation damage to nearby healthy tissue - Particularly important in ocular, brain, lung and breast cancers • Clinical evidence to support fewer side effects compared to X-rays in certain patients

So Why Only 3-10%?

• 30% of solid tumor cancer patients receive radiation (of any type) Cases suitable for proton therapy • Protons are not generally applicable for metastasized cancers – Half of the 60% are treated for palliative, versus curative, care Of 100% of cancer cases … • Limited resource 60% of these are solid tumor cases 30% of these are suitable for radiation • Cost 3-10% of these are suitable for protons • Complexity of treatment planning and delivery • Availability of proton centers

5 When Is Proton Therapy Appropriate?

Will share infographic section once final.

6 Additional Challenges • Lack of access to a proton center – Only 25 in the US (the SCCA Proton Therapy Center for the 3-10% is the only proton center in the PNW) – Typical 5-day-a-week, 6-week schedule is logistically difficult if the patient lives far away • Insurance confusion – Inconsistent coverage policies between payers – Fully covered by Medicare • May not be available in-network

7 Proton Centers in the US

SCCA Proton Therapy Center • 25 centers in operation, 2013 11 under construction Seattle, WA 1200 mi reach • Centers at Mayo Clinic, MD Anderson, Harvard and Memorial Sloan Kettering • More than 150,000 patients treated worldwide • Significant regional variation in payer coverage of protons

8 The Solution to Access in the PNW

Seattle Cancer Care Alliance Proton Therapy Center is: • A resource for the PNW medical community, offering innovative radiation treatments for solid tumor patients • Part of the Seattle Cancer Care Alliance, which harnesses the collective brain power of three world-class organizations to help people live longer, better and richer lives • Located at UW Medicine’s Northwest Hospital & Medical Center • Working closely with insurance companies and patients to develop coverage solutions

9 Who Can • Pediatric patients • Those whose tumor is very close to vital organs Benefit – Ocular cancers – Lung and left breast (the heart is very sensitive to from radiation) – CNS tumors Proton – Head and neck cancers – Chondrosarcomas/chordomas Treatment? • Re-irradiation patients • Those who have a long life expectancy after their disease and are at risk for second malignancies – Lymphomas – Younger men with prostate cancer – Women with breast cancer • Those with genetic conditions that predispose them to high toxicity when exposed to radiation

10 Protons: Where • The greatest benefit of protons is in integral radiation dose reduction. Is the – All radiation advances increase the targeting of the tumor Evidence? – Takes decades to realize this benefit • There is a lack of evidence for radiation treatment industry-wide, not just for protons. – Few long-term studies comparing modalities – While long-term toxicity is expected to be reduced (harder to measure), acute toxicity may be similar (easier to measure)

11 The best way to minimize side effects, and perhaps improve outcomes, is to eliminate any exposure of healthy tissue to treatment.

12 Protons in Pediatrics

• Radiation is of concern in children because: – Higher chance of secondary cancers due to long life expectancy post cancer – Heightened sensitivity to radiation in children

• Protons can address these concerns: – Ability to deliver an increased therapeutic dose – Less harm to nearby tissue – Ability to limit overall exposure

• Protons are standard of care for a variety of pediatric solid tumors – Medulloblastomas – Pediatric CNS tumors

13 Pediatric Neuroblastoma Patient

Protons Photons Protons Photons

Images represent a reduction in radiation to the abdomen, when using protons

14 Medulloblastoma: Craniospinal Irradiation

Protons Photons

Images represent a reduction in radiation to the entire chest and abdomen cavities, when using protons

15 Ocular Tumors Protons have been well established in the management of ocular tumors, specifically ocular melanomas. Protons Photons Previously, specialized “dedicated eye” facilities offered protons to patients with these tumors. The SCCA Proton Therapy Center is a state-of-the-art, clinically-focused facility that has a first-in-class ocular treatment program. The standard course of ocular treatment is five sessions.

Decrease in radiation exposure to underlying brain tissue, when using protons

16 There is increasing awareness that any Breast Cancer radiation dose to the heart, no matter how small, can result in an increased risk of major cardiac events during the Protons Photons lifetime of a patient. The Darby paper, a groundbreaking report in the New England Journal of Medicine, reported that any level of radiation delivered to the heart in women with breast cancer is toxic. For certain patients, protons can significantly spare the heart while allowing all critical regions to be treated. We’re participating in an ongoing effort Images represent a significant reduction in sponsored by the Patient-Centered radiation to the heart, when using protons Outcomes Research Institute (PCORI) to test this question in a multi-center, randomized trial.

17 H&N cancer cure rates with radiation Head & Neck Cancer therapy have been excellent for the past 30 years. Protons Photons The focus has been on side-effect reduction: • IMRT is a reflection of that evolution • Proton therapy, with pencil beam scanning, is another evolutionary step It provides improved conformality of the curative high-dose region and reduces the low-dose bath. This is a “win-win” for H&N patients and represents the next step forward from IMRT. Images represent a reduction in radiation We are planning to participate in a to the head and brain, when using protons randomized trial of IMRT vs. protons for H&N cancer.

18 Collaborative • Radiation – IMRT Treatment Planning – Brachytherapy – Stereotactic radiosurgery – Gamma knife The oncologists at Seattle Cancer Care Alliance – Proton therapy have expertise in all forms of cancer treatment. – Neutrons Our aim is to find the best treatment for the patient after considering all options. • Chemo • Hormone therapy • Immunotherapy • Transplant • Surgery

19 Clinical Review of Treatment Options

If radiation is the chosen treatment, then what is the best radiation approach? • An independent cancer-site tumor board review of treatment plans across modalities • A consultation review with other cancer specialists • A collaborative planning session and review with the referring physician • A comparison of the X-ray radiation treatment plan with protons • A joint recommendation to the patient in partnership with the referring physician

20 Selected Clinical Trials

Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non–Small Cell Lung Cancer: Final Results of a Phase 2 Study - by Joe Y. Chang et al. JAMA Oncol. August 20, 2017

Charged particle therapy versus photon therapy for paranasal sinus and nasal cavity malignant diseases: a systematic review and meta-analysis - by Samir H Patel et al. The Lancet, August 2014

Second Nonocular Tumors Among Survivors of Retinoblastoma Treated with Contemporary Photon and Proton Radiotherapy - by Roshan V. Sethi et al. Cancer January 1, 2014

Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer - by Sarah C. Darby et al. N Engl J Med, March 14, 2013

21 Takeaway

1 2 3 4

Protons, in some cases, The decision of whether We want to help you The SCCA Proton Therapy offer substantial clinical to use protons is a identify the 3-10% of Center is here to help benefit, particularly in collaborative effort with the patients for whom as a research, community reduction of secondary referring physician, the SCCA protons may be a and clinical resource. cancers. oncology team and the patient. consideration.

22 Thank You

Dr. Ramesh Rengan [email protected]