Proton therapy may help breast cancer patients avoid cardiotoxicity

Radiation therapy to the whole breast or chest wall and the internal mammary lymph nodes can deliver a radiation dose to the heart that increases the risk of cardiovascular events. To see whether proton therapy can reduce this risk, a multi-institutional clinical trial is comparing proton therapy to standard photon-based radiation therapy for patients with locally advanced breast cancer.

“Breast cancer patients tend to be long-term survivors,” says Karen Hoffman, M.D., an associate professor of Radiation Oncology. “They have multiple decades ahead of them in which to face the consequences of treatment.”

When a patient’s heart is irradiated, these consequences may include major cardiovascular events such as heart failure, coronary heart disease, myocardial infarction, valvular disease, arrhythmia and unstable angina.

Despite efforts to reduce the radiation dose to the heart, the risk of cardiotoxicity from standard photon-based radiation therapy for breast cancer remains.

“With the techniques we use at MD Anderson, our dose to the heart with photons is lower than published data nationally,” Hoffman says. “But protons have the potential to get that dose even lower.”

Head-to-head trial

Hoffman is MD Anderson’s principal investigator on the Phase III RAD-COMP trial (No. 2016-0085), which is enrolling patients with node-positive breast cancer who have undergone mastectomy or lumpectomy and require radiation therapy to the whole breast or chest wall and the internal mammary lymph nodes.

“Radiation therapy to the internal mammary node chain carries a high risk of cardiotoxicity because the chain runs right along the sternum,” Hoffman says.

Patients in the trial are stratified by age, baseline cardiovascular risk, type of surgery, and affected breast before randomization to ensure that equal numbers of patients in each subgroup receive proton- or photon-based treatment. Patients in both the proton and photon therapy groups receive a radiation dose of 45.0-50.4 Gy delivered in 1.8-2.0-Gy fractions.

The trial’s primary endpoint is major cardiac events, for which patients will be followed up for 10 years.

“We can look at treatment plans and agree that proton therapy delivers a lower cardiac dose than standard therapy does," says Elizabeth Bloom, M.D., a professor of Radiation Oncology and a co-investigator of the trial. “But we need to know if what we see on paper will translate into reduced long-term cardiac harm.”

The trial’s secondary endpoints include patient-reported fatigue, body image, and other quality-of-life measures. The researchers also will compare rates of locoregional control and overall survival, neither of which is expected to differ significantly between the patients treated with protons and those treated with photons.

This article originally ran in the February 2018 issue of Oncolog.