Radiation-Induced Cardiac Disease

During the third and last day of the 2021 American College of Cardiology Scientific Sessions, Dr. Marjan Boerma, PhD, Associate Professor, University of Arkansas for Medical Sciences, delivered a presentation on radiation-induced heart disease as a panelist during session 748, “Cardio-Oncology: Today’s Standard of Practice.” Aptly entitled “Unchain My Heart,” the presentation began with a focus on studies demonstrating the now well-known increased risk of heart disease as a late effect of cancer treatment in long-term survivors of Hodgkin’s lymphoma as well as in breast cancer patients who received radiotherapy for left-sided compared with right-sided breast cancers.

Dr. Boerma also discussed a combined analysis of prospective multicenter trials by Robert Dess, MD, Assistant Professor in the Department of Radiation Oncology at the University of Michigan https://pubmed.ncbi.nlm.nih.gov/28301264/ focused on patients with locally advanced non-small-cell lung cancer where radiation therapy may be critical for optimal treatment, yet also be associated with an increased risk of cardiac injury and dysfunction. Patients eligible for the study were diagnosed with stage II to III NSCLC and treated with radiation therapy from 2004 to 2013 as participants in one of four radiation therapy trials at two medical centers. The trial accrued 125 patients, and for surviving patients, the median follow-up was 51 months.

The median radiation dose provided was 70 Gy. Of the participants, 84% also received chemotherapy, and 27% had been diagnosed with pre-existing cardiac disease. The primary end point of the trial was a grade > 3 cardiac event. At a median of 11 months, 19 patients had grade > 3 cardiac events, and 11% of trial participants had grade > 3 cardiac events at a median of 24 months. The risk for grade > 3 cardiac events was significantly increased for those with pre-existing cardiac disease and higher mean radiation heart dose, where at 24 months, more than 10% of trial participants developed > 3 cardiac events. Disease progression and grade ≥ 3 cardiac events were associated with decreased overall survival. Yet the investigators reported that cancer progression was more frequent (n = 71) than grade ≥ 3 cardiac events (n = 19). Research indicates the importance of taking appropriate measures to reduce the risk of radiation-induced cardiac injury, balancing against optimal cancer control.

During her presentation, Dr. Boerma noted that different types of cardiac injury may develop secondary to radiation treatment months or several years following radiotherapy. For example, radiation-induced heart disease may manifest as coronary artery fibrosis, stenosis, and accelerated atherosclerosis; acute or chronic pericarditis; or cardiac value defects. Radiation-induced cardiac disease may develop secondary to multiple mechanisms, including smooth muscle injury, capillary endothelial dysfunction, infiltration of immune cells, growth factor and cytokine release, myofibroblast and collagen deposits, and additional mechanisms. Dr. Boerma emphasized the need for ongoing research to better understand such radiation-induced mechanisms that contribute to cardiac injury to identify safe and effective cardioprotective therapies.

She noted that radiotherapy may also interact with other cancer treatments, where patients who receive radiation as well as anthracycline-based chemotherapy have an even higher risk than with radiation alone and emphasized that an increased risk of cardiac dysfunction is also being seen with newer radiation techniques. In addition, increased cardiotoxicity has been observed when radiation therapy and immune checkpoint inhibitors are provided concomitantly, which, although rare, may increase risk for potentially life-threatening myocarditis.
Dr. Boerma concluded her presentation by outlining several important open questions to pursue with further research. These include developing a better understanding of the interaction between radiotherapy and other cancer treatments; assessing dose in changing radiation therapy modalities; identifying individuals’ susceptibility to radiation-induced cardiotoxicities; developing safe and effective cardioprotective interventions, such as further study regarding treatment with statins as a potential prophylactic therapy; and ascertaining optimal strategies for long-term cardiology care for cancer survivors.
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Marjan Boerma, PhD. “Unchain My Heart: Radiation-Induced Heart Disease.” Session 748, “Cardio-Oncology: Today’s Standard of Practice.” Presented at: American College of Cardiology Scientific Sessions; May 15-17, 2021.

Dess RT, Sun Y, Matuszak MM, Sun G, Soni PDBazzi L, et al. Cardiac events after radiation therapy: combined analysis of prospective multicenter trial for locally advanced non-small-cell lung cancer. J Clin Oncol. May 1 2017;35(12): 1395-1402. Accessed on May 17, 2021 at https://pubmed.ncbi.nlm.nih.gov/28301264/.