Brian C. Baumann, MD; James M. Metz, MD; Steven J. Frank, MD; Anita Mahajan, MD; and Jeffrey D. Bradley, MD, FACR, FASTRO

Source: https://dailynews.ascopubs.org/do/10.1200/ADN.21.200441/full/

Article Highlights:

  • As supported by emerging data, proton therapy is a high-value treatment for appropriately selected pediatric and adult patients.
  • Proton therapy reimbursement may be cut up to 50% under the new Radiation Oncology Alternative Payment Model (RO APM), placing proton centers in significant financial jeopardy and at risk for closure.
  • Proton therapy should be excluded from the RO APM to provide proton centers time to gather the necessary additional data on comparative effectiveness and to complete ongoing randomized trials to further clarify proton therapy’s value for patients with cancer.

Proton therapy is an emerging radiation treatment modality that has the potential to reduce side effects for patients by limiting the amount of normal tissue exposed to radiation. Unlike conventional x-ray radiation, which has both entrance and exit doses, proton therapy delivers radiation to the target, with little to no radiation extending beyond the target.1,2 In addition, there is at least some evidence that proton therapy may have an enhanced biologic effect on tumors over conventional x-ray therapy.3 Although proton therapy has great promise to improve disease outcomes, reduce harm, and improve quality of life for patients with cancer, it is now under financial constraints due to the Centers for Medicare & Medicaid Services’ (CMS) recent announcement of the Radiation Oncology Alternative Payment Model (RO APM).4

Dr. Brian C. Baumann

Dr. James M. Metz

The RO APM will come into effect January 2022, will last for up to 5 years, and is mandatory for 40% of all radiation oncology practices in the United States. In this new payment model, radiation oncology centers will receive a bundled payment rate based on the patient’s cancer diagnosis, regardless of the type or complexity of the radiation treatment given. The RO APM applies to common treatments, such as photon external beam radiation (e.g., 3-D conformal radiation or intensity-modulated radiation therapy [IMRT]) and brachytherapy, but is not applicable to some rare, niche radiation treatments, such as radiopharmaceuticals or intraoperative radiotherapy. The CMS, however, decided that proton therapy, a rare, emerging technology, be included in the RO APM. When the CMS was analyzing hospital radiation oncology claims to determine the proposed bundled payment rate, the reviewed claims included very few proton treatments, as proton therapy accounted for < 1% of the total sample analyzed.4,5 Given the rarity of proton therapy in the data, the rate-setting methodology described in the proposed rule would not produce national payment rates for the disease sites treated by proton beam therapy in a manner that would appropriately reimburse providers for their costs. Currently, proton therapy, as an emerging technology, is a more costly treatment because of the higher cost of the capital equipment required to deliver it, the higher cost of maintaining a proton center, and the greater complexity of proton therapy treatment planning and delivery. Expectations vary, but some have postulated that proton therapy would receive approximately a 50% cut in reimbursement under the new RO APM.4 Such a massive financial loss, incurred over 5 years, would place proton centers in significant financial jeopardy, and many would be likely to close, limiting patient access to this treatment and stifling further innovation and research on proton therapy. Although pediatric patients are excluded from the RO APM, they will nonetheless be affected, as fewer proton centers will be able to continue operations, limiting children’s access to proton therapy, which is considered the optimal delivery method of radiation for many pediatric malignancies.

Dr. Steven J. Frank

Proton therapy is a high-value treatment for appropriately selected pediatric and adult patients; however, the Center for Medicare & Medicaid Innovation has postulated that the therapy as a whole is “low-value” without acknowledging the most recent published data over the last 4 years.6 Specifically, high-quality comparative effectiveness data are now available that contradict the claim that proton therapy is “low-value.”7 Coverage policies are rapidly evolving in favor of proton therapy. For example, the Washington State Health Care Authority recently authorized the addition of proton therapy for head and neck tumors under its Health Technology Assessment program as a covered benefit because of the emerging published data.8 Furthermore, The University of Texas Health System and MD Anderson Cancer Center completed and published a study demonstrating the high value of proton therapy, which is now a covered benefit.9 In addition, technologic innovations are rapidly ensuring that proton therapy is more affordable and enabling expansion of patient access to this treatment. In our opinion, proton therapy should be excluded from the RO APM to provide proton centers time to gather the necessary additional data on comparative effectiveness and to complete ongoing randomized trials to further clarify proton therapy’s value for patients with cancer.

Dr. Anita Mahajan

In 2020, several key studies demonstrated the promise of proton therapy in making significant and clinically meaningful reductions in acute toxicity in our patients. The study by Baumann et al published in JAMA Oncology found that in a cohort of 1,483 patients with solid malignancies treated with definitive chemoradiotherapy for nonmetastatic disease, proton therapy was associated with a statistically significant two-thirds reduction in acute grade ≥ 3 adverse events on propensity weighted analysis (RR 0.31, 95% CI [0.15, 0.66]; p = 0.002) and a significant reduction in the rate of Eastern Cooperative Oncology Group (ECOG) performance status declines from the start to the end of treatment (RR 0.51, 95% CI [0.37, 0.71]; p < 0.001) compared with the photon group.1 Disease-free survival and overall survival were comparable between the two cohorts. Although the study was retrospective, the data on adverse events and survival were gathered prospectively, and 90% of the patients on the photon arm received the most advanced form of photon radiotherapy: IMRT. The cost-effectiveness implications have not been explored, but a two-thirds reduction in serious adverse events associated with hospitalizations could potentially offset the higher upfront cost of proton therapy and offers an intriguing opportunity to intensify treatments, which could, in turn, improve oncologic outcomes for patients who receive chemoradiotherapy.1,7 With fewer patients experiencing a drop in their ECOG performance status during proton chemoradiotherapy, there could be cost savings to society, as more patients would be able to work during treatment and/or handle their own self-care, freeing up their families and caretakers to remain at their jobs. In 2020, we also saw the publication of a randomized prospective trial of proton compared with photon chemoradiotherapy for esophageal cancer by Lin et al in the Journal of Clinical Oncology.10 Similar to the JAMA Oncology study, this trial found comparable oncologic outcomes but a statistically significant reduction in the primary endpoint of total toxicity burden in favor of the proton arm. Proton beam therapy was associated with 2.3-times lower total toxicity burden than photon therapy.10

In 2020, several key studies demonstrated the promise of proton therapy in making significant and clinically meaningful reductions in acute toxicity in our patients.

While the Lin et al and Baumann et al studies reported a benefit for proton therapy in reducing the risk of severe acute side effects, there is also excitement about the potential of proton therapy to limit late side effects of radiation, occurring months to years after treatment has completed. The study by Xiang et al published in Cancer reported pooled data on second malignancies from the National Cancer Database on patients with a wide range of solid malignancies treated with definitive radiotherapy (450,373 patients).11 They found that proton therapy was associated with a statistically significant two-thirds reduction in the rate of second malignancies compared with photon therapy, including in the head-to-head analysis comparing proton therapy with IMRT. There is also recent data on long-term intelligence outcomes for proton compared with photon cranial radiation. In a study by Kahalley et al in the Journal of Clinical Oncology, children treated with proton therapy for medulloblastoma exhibited superior long-term outcomes in global IQ, perceptual reasoning, and working memory compared with the photon-treated cohort (p < 0.05 for all).12

Dr. Jeffrey D. Bradley

We think there are many reasons to be excited about the promise of proton therapy and a compelling argument to be made that it is in the public’s interest to nurture proton therapy as a critical technology of the future. Government leaders have invested large subsidies into developing green energy and other technologies that are more costly than conventional options but which hold great promise to improve the environment and public health in the future. Why then would we not want to invest in a form of radiation therapy that is just as effective against cancer and exposes less of the body to radiation’s harmful effects?

We think there are many reasons to be excited about the promise of proton therapy and a compelling argument to be made that it is in the public’s interest to nurture proton therapy as a critical technology of the future.

One area where proton therapy has positioned itself as a possible treatment of the future is in the rapidly emerging field of flash radiation therapy, which has the potential to revolutionize cancer treatment. Flash radiation delivers very high–dose radiation using a much higher dose rate than conventional treatments, delivering an entire course of radiation in a matter of seconds or fractions of a second.13 The treatment remains experimental, but preclinical and very early clinical data suggest that the radiobiologic properties of flash radiation follow different principles and that comparable tumor control can be achieved with reduced toxicity.15 Flash radiation would offer the added convenience and lower cost of a single radiation treatment rather than a fractionated course of care. Proton therapy’s ability to deliver radiation to the target with minimal radiation extending beyond the target is an advantage for flash radiation when delivering very high–dose radiation in a single treatment.

There is still much work to be done to evaluate the role of proton therapy for treating patients with cancer. This is important work that should be allowed to continue so that the public can receive the best radiotherapy treatments now and, in the future, whether proton- or photon-based. Proton therapy has some clear advantages over conventional photon radiotherapy, but it is still an early technology that needs more time for research and development. We are concerned that including proton therapy in the bundled payment model will curtail the development of proton therapy before it has had a chance to realize its potential to improve public health. We strongly urge the CMS to consider removing proton therapy from the RO APM pilot study.

References

  1. Baumann BC, Mitra N, Harton JG, et al. Comparative effectiveness of proton vs photon therapy as part of concurrent chemoradiotherapy for locally advanced cancer. JAMA Oncol . 2020;6:237-246.
  2. Liao Z, Gandhi SJ, Lin SH, et al. Does proton therapy offer demonstrable clinical advantages for treating thoracic tumors? Semin Radiat Oncol . 2018;28:114-124.
  3. Wang L, Yang L, Han S, et al. Patterns of protein expression in human head and neck cancer cell lines differ after proton vs photon radiotherapy. Head Neck . 2020;42:289-301.
  4. The University of Florida Health Proton Therapy Institute. Medicare’s RO-APM Proposal. https://www.floridaproton.org/newsletter/2019/october/medicare-ro-apm-proposal. Published October 2019. Accessed December 16, 2020.
  5. The National Association for Proton Therapy. Radiation Oncology Alternative Payment Model Executive Summary. https://www.proton-therapy.org/blog/radiation-oncology-alternative-payment-model-executive-summary/. Published October 7, 2020. Accessed December 16, 2020.
  6. Medicare Payment Advisory Commission. Report to the Congress: Medicare and the Health Care Delivery System. Washington, DC: Medicare Payment Advisory Commission; 2018.
  7. Baumann BC, Hallahan DE, Michalski JM, et al. Concurrent chemo-radiotherapy with proton therapy: reduced toxicity with comparable oncological outcomes vs photon chemo-radiotherapy. Br J Cancer . 2020;123:869-870.
  8. Health Technology Clinical Committee. Findings and Decisions, in Authority WSHC (ed), 2019.
  9. Palmer MB, Ning MS, Shah AK, et al. Evidence-based access to proton therapy does not result in overutilization: 3-year results of a state-wide employer-based insurance coverage pilot. Int J Radiat Oncol Biol Phys . 2019;105:E441.
  10. Lin SH, Hobbs BP, Verma V, et al. Randomized phase iib trial of proton beam therapy versus intensity-modulated radiation therapy for locally advanced esophageal cancer. J Clin Oncol. 2020;38:1569-1579.
  11. Xiang M, Chang DT, Pollom EL. Second cancer risk after primary cancer treatment with three-dimensional conformal, intensity-modulated, or proton beam radiation therapy. Cancer . 2020;126:3560-3568.
  12. Kahalley LS, Peterson R, Ris MD, et al. Superior intellectual outcomes after proton radiotherapy compared with photon radiotherapy for pediatric medulloblastoma. J Clin Oncol . 2020;38:454-461.
  13. Diffenderfer ES, Verginadis II, Kim MM, et al. Design, implementation, and in vivo validation of a novel proton FLASH radiation therapy system. Int J Radiat Oncol Biol Phys . 2020;106:440-448.
  14. Wilson JD, Hammond EM, Higgins GS, et al. Ultra-high dose rate (FLASH) radiotherapy: silver bullet or fool’s gold? Front Oncol . 2020;9:1563.

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