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," said Karen Hoffman, M.D., an associate professor in the Department of Radiation Oncology at The University of Texas MD Anderson Cancer Center. "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," Dr. Hoffman said. "But protons have the potential to get that dose even lower."
Dr. Hoffman is MD Anderson's principal investigator of 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," Dr. Hoffman said.
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," said Elizabeth Bloom, M.D., a professor in the Department 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 will also 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.
Drs. Bloom and Hoffman said that the chief barrier to recruiting patients for the trial is convincing insurance companies to cover the more expensive proton therapy. In theory, Dr. Bloom said, insurance companies might save money in the long run if their customers could avoid long-term health problems resulting from incidental radiation to the heart, lung, contralateral breast, and shoulder girdle muscles.
"Protons can help keep the radiation where it needs to be and minimize the doses to the heart and other structures," Dr. Bloom said. "We think that this will have long-term health benefits, but we have to prove it. That's the point of this trial."
For more information, contact Dr. Elizabeth Bloom at 281-646-2244 or firstname.lastname@example.org or Dr. Karen Hoffman at 713-563-2339 or email@example.com. For more information about the RAD-COMP trial, visit www.clinicaltrials.org and search for study No. 2016-0085.
OncoLog, February 2018, Volume 63, Issue 2