Proton Beam Therapy Completes Step Toward Breast Cancer Use

Roxanne Nelson, RN, BSN

October 17, 2019

In theory, proton beam therapy may improve the safety of radiotherapy for breast cancer patients, and now clinical data provide evidence that supports further testing of the pricey, precise technology in a randomized trial to find out whether that is true.

In a single-arm, phase 2 trial with breast cancer patients, proton beam therapy yielded rates of disease control and toxicity that were similar to historical rates with standard therapy.

With the proton beam method, the 5-year rate for locoregional failure was 1.5%; for overall survival, it was 91%. There were no significant changes in echocardiography or cardiac biomarkers following treatment.

"This the first prospective study that examines the use of proton therapy for locally advanced breast cancer," said lead author Shannon MacDonald, MD, radiation oncologist and associate professor, Harvard Medical School, Boston, Massachusetts. "It was designed as a phase 2 study and not a randomized study, and the intent was to pave the way for a randomized study, which is currently underway."

The study was published in the Journal of Clinical Oncology.

Regional nodal irradiation (RNI) is given for both high-risk, early-stage and locally advanced breast cancer to reduce the risk for locoregional failure and improve disease-free survival. However, RNI includes administering radiation to the first three intercostal spaces of the internal mammary nodes, which significantly increases cardiopulmonary exposure to radiation. This in turn elevates the risk for major cardiac events; the risk is proportional to mean heart radiation dose.

There has been much interest in proton beam therapy as a means of lessening the exposure risk. Proton beam therapy offers a high degree of precision. It allows an escalated dose of radiation to be targeted directly on a tumor while sparing the adjacent healthy tissue. The use of proton beam therapy in medical settings has greatly increased during the past decade, but it remains controversial, owing to cost and to the fact that few studies have compared it with other types of radiotherapy.

In this study, MacDonald and colleagues evaluated the safety and efficacy of proton beam radiotherapy in 70 women with nonmetastatic breast cancer who required postoperative radiotherapy to the breast/chest wall and regional lymphatics. The patients were considered to be suboptimal candidates for conventional radiotherapy.

Low Toxicity, Good Disease Control

The primary endpoint was the occurrence of radiation pneumonitis of grade 3 or higher or any grade 4 toxicity within 3 months of therapy. Secondary endpoints included 5-year locoregional failure, overall survival, and acute and late toxicities.

Most patients (94%) had stage II or III breast cancer, and 93% underwent mastectomy. Virtually all patients (99%) received chemotherapy; 57% underwent neoadjuvant chemotherapy, and 13% achieved a pathologic complete response.

The median of mean delivered dose to the internal mammary nodes was 48.8 Gy (relative biological effectiveness [RBE]), the mean heart dose was a median of 0.50 Gy (RBE), and the mean dose to the left-side anterior descending artery was a median of 1.16 Gy (RBE).

None of the patients experienced any type of grade 4 or 5 toxicity, and there was no occurrence of radiation pneumonitis of grade 3 or higher in the cohort. One patient developed grade 2 radiation pneumonitis. The most common adverse event was skin dermatitis (83%).

With regard to cardiac events, no significant decreases in global longitudinal strain or left ventricular ejection fraction and no significant increases in circulating biomarkers were observed in any patient. The authors note that the "final analyses of the strain portion of the echocardiograms to assess for subclinical cardiac strain changes for the entire cohort, along with circulating cardiac biomarkers, will be reported separately."

For the secondary endpoints, at a median follow-up of 55 months, eight patients experienced a distant relapse (crude distant failure rate, 12%). The distant metastasis–free survival was 86%. The estimated 5-year overall survival was 91%.

MacDonald pointed out that she is the clinical primary investigator of RADCOMP (Randomized Trial of Proton vs Photon Therapy for Patients with Non-Metastatic Breast Cancer Receiving Comprehensive Nodal Radiation), which is "designed to show if there is a benefit in decreased cardiac toxicity from proton therapy and the hypothesis is that there will be.

"This study is a PCORI [Patient-Centered Outcomes Research Institute]–sponsored multi-institutional trial that is open at 65 centers and 22 proton centers and has accrued over 700 patients to date," she said.

Paving the Way

Commenting on the study, Richard Bakst, MD, associate professor of radiation oncology at the Icahn School of Medicine at Mount Sinai, New York City, noted that the results of this study are encouraging but that the follow-up was only for 5 years. "This is a start to gathering data, but it isn't long enough to make any conclusions about heart and lung exposures," he said. "We are looking more at the late effects, and I think people are going to want to see 10- and 15-year data."

Bakst explained that breast cancer patients are being treated with proton beam therapy, and it's "used clinically on a case-by-case basis."

However, insurers may not be willing to provide coverage because the use of proton beam radiotherapy has not been well studied in breast cancer. "Insurance coverage is a moving target," he said. "Sometimes they cover and sometimes not."

The study was supported by a grant from the National Institutes of Health. MaDonald has disclosed no relevant financial relationships. Several coauthors have disclosed relationships with industry, as noted in the article. Bakst has reported no relevant financial relationships.

J Clin Oncol. 2019;37:2778-2785. Abstract

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