Proton Therapy Improves Outcomes, Reduces Radiation Side Effects in Patients with Cancer

Many patients with cancer and oncologists may not have heard about proton therapy, an advanced form of radiation therapy to target cancerous cells. The use of proton therapy is growing thanks to its potentially reduced side-effect profile compared with standard radiation, improved patient outcomes, and new proton therapy centers across the country. For many patients with difficult-to-treat cancer, this treatment brings new hope for potentially improving their outcomes and quality of life.

Proton therapy was approved by the FDA for cancer in 1988. In the past, few proton radiation centers were built in the United States, because of the high financial investment required, lack of expertise, and most were located within a few academic centers, which hindered patient access to them. Today, the cost has significantly decreased, which is encouraging the growth of new centers, increasing patient access to this newer type of radiation. More than 75,000 patients with cancer in the United States have received proton treatment by now.¹

What Is Proton Therapy?

Proton therapy is a form of radiation, but it differs from traditional (photon) radiation that uses x-rays or gamma rays. Traditional radiation directly targets the tumor, but it also delivers radiation into healthy tissues surrounding the tumor, which exposes those healthy tissues to unnecessary radiation. This unavoidable exposure of healthy tissue to radiation can lead to short-term and long-term side effects, and the development of secondary tumors.

By contrast, proton therapy delivers up to 60% less radiation to adjacent tissues than traditional radiation and deposits the majority of the radiation directly into the tumor, and then stops.² Almost no radiation is delivered beyond the tumor, which reduces the harmful side effects.

Reduced Side Effects

A growing body of evidence demonstrates that proton therapy lowers the risk for side effects compared with traditional radiation. As a result of its superior beam characteristics, proton therapy has been used for the treatment of pediatric cancers and has been shown to reduce short- and long-term side effects in those patients.³

But proton therapy has also shown benefits in adults. For example, in a recent study, proton therapy led to about a 66% reduction in hospitalizations compared with traditional radiation, but the cure rates were almost identical.⁴ Studies have also shown that an advanced form of proton therapy called “intensity-modulated proton therapy” can reduce side effects in patients with head and neck cancer.⁵

There is also evidence that proton therapy reduces the risk of secondary cancers that can result from standard radiation.^1,6 Secondary cancers are a serious concern for patients, especially in cancer survivors today, who are living longer, and longer survival duration may increase the risk for secondary cancers.⁷ A recent study showed that compared with intensity-modulator radiotherapy (IMRT) with photons, proton therapy can reduce the risk of second cancers by at least 50% in many cases.⁸

Patients receiving proton therapy may still have discomfort during and after treatment; fatigue and skin problems, such as redness, irritation, dryness, swelling, or blistering, may occur with proton therapy, especially if the tumor is near the skin surface.²

Patients who receive combined treatment with chemotherapy and radiation may have fewer side effects if proton therapy is used instead of standard radiation in many cancer types.⁹ A recent randomized clinical trial showed that patients receiving chemotherapy and radiation therapy, with or without surgery, for esophageal cancer had fewer major adverse events if they were treated with proton therapy instead of IMRT.¹⁰

Improved Patient Outcomes

Promising benefits of proton therapy have been documented in several areas, as described below. As this therapy becomes more common, its benefits may be better understood.

Pediatric cancer. Children are very sensitive to radiation, even at low doses, which can harm developing tissues. Exposing developing tissue to standard radiation therapy can have lifelong consequences. Proton therapy can reduce these harmful side effects and minimize the long-term damage. This also applies to young adults, and even to middle-aged and older patients.

Human papillomavirus (HPV)-­related head and neck cancers typically affect young adults. The treatment of these cancers often includes chemotherapy and radiation, which can have serious, and sometimes lifelong, side effects. Proton therapy can reduce these side effects in young adults and improve patients’ long-term quality of life.

Combination therapies. An increasing number of patients with cancer are receiving combined therapies that include chemotherapy, radiation, and surgery. Again, proton therapy can lessen the impact of these combined therapies, by minimizing the side effects on vulnerable organs, such as the heart and lungs.

An alternative to standard radiation therapy. The number of radiation treatments can be reduced if a higher daily dose is used, but clinical trials have shown that shorter treatment regimens may result in more side effects, unless advanced radiation therapy techniques are used. Proton therapy may offer an alternative therapy, provide better long-term outcomes, and cost-savings, by reducing the treatment-related side effects and their costs and inconvenience for patients.

Costs and Insurance

Currently, proton therapy can be more costly than standard radiation, so there is resistance by insurance companies to cover it.¹¹ However, these cost estimates are often overestimated and don’t consider the costs related to the treatment of side effects caused by standard radiation, which can be lifelong.¹¹ For example, patients with cancer today may live many years after treatment, which can result in a substantial cost for them if they require treatment for lifelong side effects. Because proton therapy significantly reduces side effects, it can lower long-term costs during survivorship.¹¹

Medicare usually covers proton therapy for most cancer types, but coverage denials are common among private health insurance companies. According to a recent study, about 66% of patients with private health insurance initially had their requests for proton therapy denied. When the patients appealed these denials, about 68% of the requests were eventually approved.¹¹

Another study showed an 87% insurance approval rate; however, appealing a coverage denial caused significant delays in treatment and was costly.¹² Patients should coordinate with a financial counselor at their proton therapy center to work with their insurance plan to determine their benefits before treatment.

New Developments

Recent exciting research and innovations in proton therapy are propelling this technology further into mainstream cancer care. These ongoing advancements will likely provide new ways to deliver proton beams to patients. For example, pencil beam scanning is a major improvement in proton-beam delivery of tiny beams that are only millimeters wide. Each beam can be controlled tightly, which provides precise coverage of all 3 dimensions (3-D) of the tumor.¹³

Other technical advancements can help to deliver more complex proton treatments, which will enable us to provide treatment for more complicated cancers. New imaging developments allow providers to target the tumor accurately, including the ability to do 3-D targeting with cone-beam CT, while the patient is on the treatment table. This provides a full 3-D image of the tumor and surrounding area, which further improves the treatment accuracy.

As noted earlier, proton technology is becoming more precise, more powerful, and less expensive to develop. It may also improve the patient’s ability to mount an immune response against tumor cells, while avoiding triggering of the immunosuppressive effects that photon therapy can cause.¹⁴ If this research holds true, proton therapy may play a vital role in combination with immunotherapy.

With progress, the cost to build proton therapy facilities will continue to be reduced. As the benefits of this new technology are becoming more apparent, many of the critics of this new technology have become proton users. Many providers who were critical of proton therapy 5 or 10 years ago now have their own proton center or intend to develop one. We are continuing to expand our understanding of how this powerful technology can be used to advance cancer care and improve patients’ lives.

References

1. The National Association for Proton Therapy. Proton therapy fact sheet. Updated 2020. www.proton-therapy.org/patient-resources/fact-sheet/.
2. Cancer.net. Proton therapy. www.cancer.net/navigating-cancer-care/how-cancer-treated/radiation-therapy/proton-therapy.
3. Grosshans DR. Proton therapy for paediatric medulloblastoma. Lancet Oncol. 2016;3:258-259.
4. University of Pennsylvania School of Medicine. Proton therapy lowers risk of side effects in cancer compared to traditional radiation. Science Daily. December 26, 2019. www.sciencedaily.com/releases/2019/12/191226134054.htm.
5. McKeever MR, Sio TT, Gunn GB. Reduced acute toxicity and improved efficacy from intensity-modulated proton therapy (IMPT) for the management of head and neck cancer. Chin Clin Oncol. 2016;5(4):54.
6. Eaton BR, MacDonald SM, Yock TI, Tarbell NJ. Secondary malignancy risk following proton radiation therapy. Frontiers in Oncology. 2015;5:261.
7. Dracham CB, Shankar A, Madan R. Radiation induced secondary malignancies: a review article. Radiation Oncology Journal. 2018;36(2):85-94.
8. Xiang M, Change DT, Pollom EL. Second cancer risk after primary cancer treatment with three-dimensional conformal, intensity-modulated, or proton beam radiation therapy. Cancer. 2020 May 19. Online ahead of print.
9. Bauman 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. 2019;6:237-246.
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. Rochman S. Focusing on proton therapy. Cancer Today. June 21, 2019. www.cancertodaymag.org/Pages/Summer2019/Focusing-on-Proton-Therapy.aspx.
12. Ning MS, Gomez DR, Shah AK, et al. The insurance approval process for proton radiation therapy: a significant barrier to patient care. International Journal of Radiation Oncology, Biology Physics. 2019;104(4):724-733.
13. ProTom International. Advantages of Pencil Beam Scanning. November 16, 2017. www.protominternational.com/2017/11/advantages-of-pencil-beam-scanning/.
14. Lee HJ Jr, Zeng J, Rengan R. Proton beam therapy and immunotherapy: an emerging partnership for immune activation in non-small cell lung cancer. Translational Lung Cancer Research. 2018;7(2):180-188.