Cardiovascular Event Reporting in Modern Cancer Radiation Therapy Trials

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in cancer survivors, particularly after chest radiation therapy (RT). However, the extent to which CVD events are consistently reported in contemporary prospective trials is unknown.

From 10 high-impact RT, oncology, and medicine journals, we identified all latter phase trials from 2000 to 2019 enrolling patients with breast, lung, lymphoma, mesothelioma, or esophageal cancer wherein chest-RT was delivered. The primary outcome was the report of major adverse cardiac events (MACEs), defined as incident myocardial infarction, heart failure, coronary revascularization, arrhythmia, stroke, or CVD death across treatment arms. The secondary outcome was the report of any CVD event. Multivariable regression was used to identify factors associated with CVD reporting. Pooled annualized incidence rates of MACEs across RT trials were compared with contemporary population rates using relative risks (RRs).

The 108 trials that met criteria enrolled 59,070 patients (mean age, 58.0 ± 10.2 years; 46.0% female), with 273,587 person-years of available follow-up. During a median follow-up of 48 months, 468 MACEs were reported (including 96 heart failures, 75 acute coronary syndrome, 1 revascularization, 94 arrhythmias, 28 strokes, and 20 CVD deaths; 307 occurred in the intervention arms vs 144 in the control arms; RR, 1.96; P < .001). Altogether, 50.0% of trials did not report MACEs, and 37.0% did not report any CVD. The overall weighted-trial incidence was 376 events per 100,000 person-years compared with 1408 events per 100,000 person-years in similar nontrial patients (RR, 0.27; P < .001). There were no RT factors associated with CVD reporting.

In contemporary chest RT-based clinical trials, reported CVD rates were lower than expected population rates.