Left Anterior Descending Coronary Artery Radiation Dose Association With All-Cause Mortality in NRG Oncology Trial RTOG 0617

Purpose: A left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15 Gy) >= 10% has been recently observed to be an independent risk factor of major adverse cardiac events and all-cause mortality in patients with locally advanced non-small cell lung cancer treated with radiation therapy. However, this dose constraint has not been validated in independent or prospective data sets. Methods and Materials: The NRG Oncology/Radiation Therapy Oncology Group (RTOG) 0617 data set from the National Clinical Trials Network was used. The LAD coronary artery was manually contoured. Multivariable Cox regression was per-formed, adjusting for known prognostic factors. Kaplan-Meier estimates of overall survival (OS) were calculated. For assess-ment of baseline cardiovascular risk, only age, sex, and smoking history were available.Results: There were 449 patients with LAD dose-volume data and clinical outcomes available after 10 patients were excluded owing to unreliable LAD dose statistics. The median age was 64 years. The median LAD V15 Gy was 38% (interquartile range, 15%-62%), including 94 patients (21%) with LAD V15 Gy <10% and 355 (79%) with LAD V15 Gy >= 10%. Adjusting for prog-nostic factors, LAD V15 Gy >= 10% versus <10% was associated with an increased risk of all-cause mortality (hazard ratio [HR], 1.43; 95% confidence interval, 1.02-1.99; P = .037), whereas a mean heart dose >= 10 Gy versus <10 Gy was not (adjusted HR, 1.12; 95% confidence interval, 0.88-1.43; P = .36). The median OS for patients with LAD V15 Gy >= 10% versus <10% was 20.2 versus 25.1 months, respectively, with 2-year OS estimates of 47% versus 67% (P = .004), respectively.Conclusions: In a reanalysis of RTOG 0617, LAD V15 Gy >= 10% was associated with an increased risk of all-cause mortality. These findings underscore the need for improved cardiac risk stratification and aggressive risk mitigation strategies, including implementa-tion of cardiac substructure dose constraints in national guidelines and clinical trials. (c) 2022 Elsevier Inc. All rights reserved.