Abstract
PURPOSE: Cardiotoxicity is a major concern for patients undergoing thoracic radiation therapy. This study compared the predictive power of radiation dose-volume histogram (DVH) parameters and radiomic/dosiomic features of the whole heart (WH) and cardiac substructures for elevated circulating high-sensitivity cardiac troponin T (hs-cTnT), a biomarker for early detection of cardiac adverse events. METHODS AND MATERIALS: A retrospective cohort of 160 patients with non-small cell lung cancer (NSCLC) from a completed prospective trial and a prospective cohort of 57 patients with NSCLC enrolled in an ongoing trial were analyzed. The endpoint was hs-cTnT elevation, indicated by an increase of ≥5 ng/L from baseline. An in-house auto-segmentation model delineated 19 cardiac substructures. DVH parameters, radiomic, and dosiomic features were extracted from each patient. A 100-iteration Monte Carlo cross-validation (75%/25% split) was conducted within the retrospective cohort to mitigate random split bias. Logistic regression models using different input combinations were compared, with a model using only clinical factors serving as the baseline. Key predictive features were identified using permutation importance during training. Models were validated by holdout in the prospective cohort to evaluate robustness. Model performance was assessed by the area under the receiver operating characteristic curve (AUROC). RESULTS: Incidence of hs-cTnT elevation was 31.9% in the retrospective and 29.8% in the prospective cohort. The substructure DVH model achieved the highest predictive performance in cross-validation (mean AUROC, 0.71; 95% CI, 0.70-0.73) and demonstrated greater robustness in holdout validation compared with WH-based models (AUROC: 0.60 vs ≤0.51). Feature analysis identified the left anterior descending coronary artery V20Gy as the most dominant predictor, with cutoff values ranging from 0.2% to 5% using various indices. CONCLUSIONS: Cardiac substructure DVH parameters have superior predictive power and robustness over WH variables for predicting hs-cTnT elevation in NSCLC radiation therapy, emphasizing the need to use cardiac substructures for cardiotoxicity risk assessment.