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.

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Finding the 3% Your challenge: Proton therapy is appropriate in only 3-10% of solid tumor cases.

But for that group, there are many expected clinical benefits.

How can I make sure that

my patient is getting the best treatment plan?

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• 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

Clinical Benefits of Proton Therapy

So Why Only 3-10%? • 30% of solid tumor cancer patients receive radiation (of any type)

• Protons are not generally applicable for metastasized cancers – Half of the 60% are treated for palliative, versus curative, care

• Limited resource

• Cost

• Complexity of treatment planning and delivery

• Availability of proton centers

Of 100% of cancer cases …

60% of these are solid tumor cases

30% of these are suitable for radiation

3-10% of these are suitable for protons

Cases suitable for proton therapy

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When Is Proton Therapy Appropriate?

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Will share infographic section once final.

Additional Challenges for the 3-10% • Lack of access to a proton center

– Only 25 in the US (the SCCA Proton Therapy Center 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

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Proton Centers in the US

• 25 centers in operation, 11 under construction

• 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

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SCCA Proton Therapy Center 2013 Seattle, WA 1200 mi reach

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

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Who Can Benefit from Proton Treatment?

• Pediatric patients

• Those whose tumor is very close to vital organs – Ocular cancers – Lung and left breast (the heart is very sensitive to

radiation) – CNS tumors – Head and neck cancers – Chondrosarcomas/chordomas

• 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

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Protons: Where Is the Evidence?

• The greatest benefit of protons is in integral radiation dose reduction. – All radiation advances increase the targeting of the

tumor – 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)

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The best way to minimize side effects, and perhaps improve

outcomes, is to eliminate any exposure

of healthy tissue to treatment.

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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

Pediatric Neuroblastoma Patient

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

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Protons Photons Protons Photons

Medulloblastoma: Craniospinal Irradiation

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

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Protons Photons

Ocular Tumors Protons have been well established in the management of ocular tumors, specifically ocular melanomas.

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.

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Protons Photons

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

Breast Cancer There is increasing awareness that any radiation dose to the heart, no matter how small, can result in an increased risk of major cardiac events during the 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 sponsored by the Patient-Centered Outcomes Research Institute (PCORI) to test this question in a multi-center, randomized trial.

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Protons Photons

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

Head & Neck Cancer H&N cancer cure rates with radiation therapy have been excellent for the past 30 years.

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.

We are planning to participate in a randomized trial of IMRT vs. protons for H&N cancer.

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Protons Photons

Images represent a reduction in radiation to the head and brain, when using protons

Collaborative Treatment Planning

• Radiation – IMRT – Brachytherapy – Stereotactic radiosurgery – Gamma knife – Proton therapy – Neutrons

• Chemo

• Hormone therapy

• Immunotherapy

• Transplant

• Surgery

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The oncologists at Seattle Cancer Care Alliance have expertise in all forms of cancer treatment. Our aim is to find the best treatment for the patient after considering all options.

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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

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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

Takeaway

Protons, in some cases, offer substantial clinical benefit, particularly in reduction of secondary cancers.

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1 2 3 4 The decision of whether to use protons is a collaborative effort with the referring physician, the SCCA oncology team and the patient.

We want to help you identify the 3-10% of patients for whom protons may be a consideration.

The SCCA Proton Therapy Center is here to help as a research, community and clinical resource.

Thank You

Dr. Ramesh Rengan rengan@uw.edu