The Impact of Radiation Dose to Heart Substructures on Major Coronary Events and Patient Survival after Chemoradiation Therapy for Esophageal Cancer

SIMPLE SUMMARY: Whether it is necessary to evaluate the radiation exposure of cardiac substructures when making radiotherapy plans is one of the current research hotspots. In this cohort study of 355 patients with esophageal cancer, the radiation dose to key coronary substructures such as the left anterior descending artery V30(Gy) and mean left main coronary artery was closely associated with major coronary events and overall patient survival, and showed better predictive value than the mean heart dose or heart V30(Gy) recommended by current guidelines. Our findings suggest that, in addition to the whole heart, key coronary substructures should be contoured as organs at risk during radiotherapy plan optimization. ABSTRACT: Background: There is a paucity of data regarding the association between radiation exposure of heart substructures and the incidence of major coronary events (MCEs) in patients with esophageal cancer (ESOC) undergoing chemoradiation therapy. We studied radiation dosimetric determinants of MCE risk and measured their impact on patient prognosis using a cohort of ESOC patients treated at a single institution. Methods: Between March 2005 and October 2015, 355 ESOC patients treated with concurrent chemoradiotherapy were identified from a prospectively maintained and institutional-regulatory-board-approved clinical database. Dose-distribution parameters of the whole heart, the atria, the ventricles, the left main coronary artery, and three main coronary arteries were extracted for analysis. Results: Within a median follow-up time of 67 months, 14 patients experienced MCEs at a median of 16 months. The incidence of MCEs was significantly associated with the left anterior descending coronary artery (LAD) receiving ≥30 Gy (V30(Gy)) (p = 0.048). Patients receiving LAD V30(Gy) ≥ 10% of volume experienced a higher incidence of MCEs versus the LAD V30(Gy) < 10% group (p = 0.044). The relative rate of death increased with the left main coronary artery (LMA) mean dose (Gy) (p = 0.002). Furthermore, a mutual promotion effect of hyperlipidemia and RT on MCEs was observed. Conclusion: Radiation dose to coronary substructures is associated with MCEs and overall survival in patients with ESOC. In this study, the doses to these substructures appeared to be better predictors of toxicity outcomes than mean heart dose (MHD) or whole-heart V30(Gy). These findings have implications for reducing coronary events through radiation therapy planning.