Cardiac Substructures Dosimetric Predictors for Cardiac Toxicity After Definitive Radiotherapy in Esophageal Cancer.

PURPOSE:To investigate the predictive value of the cardiac substructures (CSs) dosimetric parameters for cardiac toxicity after definitive radiation therapy in locally advanced esophageal cancer. METHODS AND MATERIALS:Between August 2010 and January 2016, 716 patients with stage 2-3 esophageal cancer receiving definitive radiation therapy at 2 institutions were divided into training (n = 432) and external validation (n = 284) cohorts. Dose-volume histogram parameters for the whole heart (WH) and CSs were extracted. Competing risks and Cox regressions analyses were performed. The predictive performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC) and the Brier score. RESULTS:With a median follow-up of 93 months, 68 patients (15.7%) developed grade ≥3 cardiac events (G3+ CEs), with a median of 13.5 months to the first event. Multivariable analysis showed left ventricle, left anterior descending (LAD), and mean left circumflex (LCX) variables were significantly associated with G3+ CEs. The AUCs and Brier scores demonstrated favorable predictive accuracies of the models integrating these CS variables when predicting G3+ CEs in the training and validation cohorts. However, compared with the WH variables, the CS variables did not significantly improve the prediction of G3+ CEs. Nevertheless, when G3+ acute coronary syndrome and/or congestive heart failure (ACS/CHF) CE was the outcome of interest, models based on the LAD or LCX variables were superior to the WH variable models in training and validation cohorts. CONCLUSIONS:Models based on CS variables showed favorable predictive accuracy for G3+ CEs. The LAD and LCX variables significantly improved the prediction of G3+ ACS/CHF events compared with the WH variables. Radiation doses to CSs, such as LCX and LAD, should be monitored to help reduce the occurrence of significant CEs in patients with esophageal cancer undergoing definitive radiation therapy.