Radiotherapy for lung cancer elevates risk of MACE, mortality

Cardiac radiation dose exposure is a modifiable cardiac risk factor for major cardiac adverse events (MACE) and all-cause mortality in patients undergoing radiotherapy for non-small-cell lung cancer (NSCLC), researchers report in the Journal of the American Heart Association.

First author Katelyn M. Atkins, MD, PhD, of the Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, and colleagues studied a cohort of 748 consecutive locally advanced NSCLC patients in an effort to understand the extent to which radiation therapy can affect MACE in cancer patients. Cardiotoxicity after radiotherapy has been noted in long-term breast cancer and Hodgkin lymphoma survivors, but those cancers typically see higher survival rates than lung cancer, one of the biggest killers in the U.S.

“Thus, the clinical relevance of radiotherapy-associated cardiac toxicity in locally advanced NSCLC patients has historically been minimized given the competing risk of cancer-specific death and presumption of prolonged latency to cardiotoxicity,” Atkins et al. wrote in JAHA.

The authors retrospectively tracked their study population through an average of 20.4 months, during which period 77 patients developed at least one marker of MACE. Five hundred thirty-three patients—nearly three-quarters of the original cohort—died during follow-up.

Atkins and co-authors reported that the two-year cumulative incidence of MACE was 5.8% in their subjects, and mean radiation dose delivered to the heart (mean heart dose) was linked to a significantly increased risk of MACE and all-cause mortality. Mean heart dose increased the risk of MACE at a hazard ratio (HR) of 1.05/Gy and the risk of all-cause mortality at an HR of 1.02/Gy.

Mean heart dose, which was individually calculated for each patient and defined as the mean radiation dose delivered to the whole heart by completion of radiotherapy, ranged anywhere from 10 Gy or greater to less than 10 Gy. It was associated with an increased risk of all-cause mortality in CHD-negative patients (178 vs. 118 deaths), with two-year estimates of 52.2% versus 40%. CHD-positive patients saw a two-year all-cause death estimate of 54.6% versus 50.8%.

The authors said their study “strongly suggests” that, despite the competing risk of cancer-specific death and short life expectancy, NSCLC patients see a high risk for MACE within two years of radiotherapy. Cardiac radiation dose seemed to be an independent predictor of MACE and all-cause mortality, but Atkins and colleagues said further prospective studies will need to assess the effect of combined cardiac risk stratification, cardiac radiation dose reduction techniques and post-radiation preventive care on NSCLC patients’ survival and quality of life.

“The results of this study highlight the importance of early recognition and treatment of cardiovascular events and inform the design of future prospective trials that incorporate baseline cardiac risk stratification with cardiac radiation dose reduction techniques and post-radiotherapy cardiac preventative care,” the authors wrote. “Indeed, as cardiac dose exposure is a modifiable predictor, we suggest more stringent avoidance of high cardiac radiotherapy dose and reconsideration of stricter cardiac radiation dose constraints in national radiotherapy guidelines.”