Low-Dose Cardiac Exposure (Heart V5) as an Independent Predictor of Radiation-Induced Pericarditis in Breast Cancer: An Interpretable Machine Learning Study

Background In breast cancer treatment, high-dose cardiac irradiation has traditionally been the focus, but growing evidence suggests that even low-dose radiation can cause long-term cardiac damage, raising concerns about radiation-induced heart disease (RIHD) and pericarditis as significant survivorship issues. Understanding dosimetric predictors like low-dose cardiac exposure (heart_V5) is critical for optimizing treatment safety. Methods A retrospective cohort study was conducted from January 2022 to June 2023, involving 277 female breast cancer patients (training n = 224, test n = 53). Radiation-induced pericarditis risk, the primary outcome, was derived from an NTCP model binarized at 3.8487×10⁻⁶ to classify the top 25% as high-risk. Key exposure was heart_V5 (median 31.5%, IQR 21.9–42.2), and analytics included preprocessing, six machine-learning models (XGBoost best-performing) with 5-fold cross-validation, DeLong test for AUC comparison, and SHAP for model interpretation. Results On the independent test set (n = 53), the XGBoost model achieved superior performance, with an area under the receiver operating characteristic curve (AUC) of 0.918 (95% CI 0.848–0.987), an accuracy of 0.925, a recall of 0.727, and an F1-score of 0.800. Critically, to isolate the impact of low-dose radiation, a simplified XGBoost model excluding high-dose features was developed. This model maintained high predictive power (AUC = 0.903), underscoring the significant, independent predictive value of low-dose cardiac exposure (heart_V5). In this simplified model, heart_V5 was a top-three predictor, demonstrating a non-linear dose-response relationship. While high-dose metrics (heart_V30, heart_V40) were the dominant predictors in the full model, the strong performance of the simplified model confirms that heart_V5 is a key factor for pericarditis risk. Furthermore, heart_V5 was significantly correlated with the mean heart dose (Pearson r = 0.75, p < 0.001). Conclusions Low-dose cardiac exposure (heart_V5) demonstrates independent predictive value for radiation-induced pericarditis when high-dose features are controlled, suggesting its consideration in radiotherapy planning to reduce late pericardial morbidity.