Long-term risk of major cardiac events in breast cancer patients treated with intensity-modulated and 3-dimensional conformal radiotherapy: Secondary analysis of a randomized clinical trial.

We assess the relationship between radiation dose to the heart and cardiac disease within the context of modern radiotherapy techniques of 3-dimensional and intensity-modulated radiotherapy (IMRT). The KROG 15-03 study was a multicenter phase III trial involving 693 breast cancer patients who underwent breast-conserving surgery (BCS). Patients were randomly assigned to receive either IMRT or 3D-CRT following BCS. Major cardiac event (MCE), defined as the occurrence of angina pectoris or myocardial infarction requiring coronary angiography, and admission for cardiac arrhythmia related to the irradiation of the heart. The primary outcome of the study was to investigate the incidence of MCE and factors associated with MCEs. At a median follow-up of 6.5 years, the incidence of MCEs at 6.5 years was 1.8%. The mean heart dose (MHD) for the entire cohort of 647 patients was 2.1 (±2.3) Gy. The cumulative incidence of MCEs at 6.5 years was 1.1% for the subgroup of MHD <2.9 Gy and 3.3% for the subgroup of MHD >2.9 Gy (p = 0.010), and 0.9% for the subgroup of age ≤55 years and 3.3% for the subgroup of age >55 years (p = 0.006), respectively. Multivariate analyses confirmed that MHD (p = 0.044; hazard ratio [HR], 1.21 per 1 Gy; 95% confidence interval [CI], 1.09-1.46) and age (p = 0.034; HR, 1.07 per 1 year; 95% CI, 1.03-1.14) were significant factors of MCEs. The incidence of MCE increased by 21% per 1-Gy increase in MHD within 6.5 years after radiotherapy.