Beyond mean heart dose: differentiated electrocardiographic manifestations and dosimetric mechanisms of cardiac injury in left-sided versus right-sided breast cancer after intensity-modulated radiotherapy

Objective To investigate dosimetric exposure variations to the whole heart and substructures between left- and right-sided breast cancer patients receiving intensity-modulated radiotherapy (IMRT), and to evaluate their relationships with post-radiotherapy (post-RT) electrocardiogram (ECG) alterations. Methods Clinical and dosimetric data of 91 breast cancer patients (54 left-sided, 37 right-sided) undergoing postoperative free-breathing IMRT were retrospectively analyzed. Twelve-lead ECGs were regularly monitored during follow-up. Kaplan-Meier analysis evaluated ECG abnormality-free survival. Receiver operating characteristic (ROC) curves compared the predictive values of mean heart dose (MHD) and left ventricular mean dose (LV D mean ) for new-onset repolarization abnormalities in left-sided patients, utilizing mathematically derived population-specific split-points. Results Target volume configurations (comprehensive regional and internal mammary node irradiation) drove distinct substructure exposure patterns between sides. In left-sided patients, MHD, LV, and left anterior descending artery (LAD) doses were significantly higher than those in right-sided patients (all P < 0.001). Conversely, right-sided patients sustained significantly higher doses to the sinoatrial node (SAN) and right coronary artery (RCA) (all P < 0.001). Left-sided patients had a significantly shorter median ECG abnormality-free survival than right-sided patients (7.0 vs. 12.0 months, P = 0.038). Among the 60 patients developing post-RT ECG modifications (incidence: 81.5% in left-sided cases), left-sided cases predominantly exhibited repolarization abnormalities (68.2%), whereas right-sided cases primarily presented rhythm abnormalities (62.5%, P = 0.032). In the left-sided subgroup, LV dosimetric parameters (LV D mean , LV V 5 – V 80 ) were significantly higher in the repolarization group than in the rhythm group (all P < 0.01). ROC analysis indicated that LV D mean outperformed MHD in predicting early repolarization changes (AUC: 0.776 vs. 0.715). Conclusion Early post-RT cardiotoxicity follows a laterality-specific “dual-mechanism model.” Left-sided modifications manifest primarily as acute/subacute repolarization surrogates driven by diffuse LV exposure, whereas right-sided modifications present as rhythm-based stress from focal SAN exposure.