Cardiac Adverse Events Associated With Chemo‐Radiation Versus Chemotherapy for Resectable Stage III Non‐Small‐Cell Lung Cancer: A Surveillance, Epidemiology and End Results‐Medicare Study

BACKGROUND: We compared cardiac outcomes for surgery‐eligible patients with stage III non‐small‐cell lung cancer treated adjuvantly or neoadjuvantly with chemotherapy versus chemo‐radiation therapy in the Surveillance, Epidemiology and End Results‐Medicare database. METHODS AND RESULTS: Patients were age 66+, had stage IIIA/B resectable non‐small‐cell lung cancer diagnosed between 2007 and 2015, and received adjuvant or neoadjuvant chemotherapy or chemo‐radiation within 121 days of diagnosis. Patients having chemo‐radiation and chemotherapy only were propensity‐score matched and followed from day 121 to first cardiac outcome, noncardiac death, radiation initiation by patients who received chemotherapy only, fee‐for‐service enrollment interruption, or December 31, 2016. Cause‐specific hazard ratios (HRs) and competing risks subdistribution HRs were estimated. The primary outcome was the first of these severe cardiac events: acute myocardial infarction, other hospitalized ischemic heart disease, hospitalized heart failure, percutaneous coronary intervention/coronary artery bypass graft, cardiac death, or urgent/inpatient care for pericardial disease, conduction abnormality, valve disorder, or ischemic heart disease. With median follow‐up of 13 months, 70 of 682 patients who received chemo‐radiation (10.26%) and 43 of 682 matched patients who received chemotherapy only (6.30%) developed a severe cardiac event (P=0.008) with median time to first event 5.45 months. Chemo‐radiation increased the rate of severe cardiac events (cause‐specific HR: 1.62 [95% CI, 1.11–2.37] and subdistribution HR: 1.41 [95% CI, 0.97–2.04]). Cancer severity appeared greater among patients who received chemo‐radiation (noncardiac death cause‐specific HR, 2.53 [95% CI, 1.93–3.33] and subdistribution HR, 2.52 [95% CI, 1.90–3.33]). CONCLUSIONS: Adding radiation therapy to chemotherapy is associated with an increased risk of severe cardiac events among patients with resectable stage III non‐small‐cell lung cancer for whom survival benefit of radiation therapy is unclear.