Abstract
INTRODUCTION: This study aimed to evaluate the efficacy of the mean heart dose (MHD) as a predictor of radiation exposure to cardiac substructures and its association with markers of subclinical cardiotoxicity in breast cancer (BC) patients undergoing radiotherapy (RT). Although MHD provides an overall estimate of cardiac exposure, it does not capture the heterogeneous dose distribution across critical cardiac substructures. MATERIALS AND METHODS: In an ambispective study design, dosimetric parameters, including MHD and dose-volume metrics for the left anterior descending artery (LAD), left circumflex artery (LCx), and left main coronary artery (LMCA), were analyzed in a cohort of BC patients receiving adjuvant RT. Early cardiotoxicity markers, such as N-terminal pro-B-type natriuretic peptide (NT-proBNP), ejection fraction (EF), and the Tei index, were evaluated. The relationship between MHD and radiation doses to specific cardiac substructures, as well as their association with cardiac biomarker levels, was assessed. RESULTS: Among 104 patients, the overall MHD was 6.4 ± 5.4 Gy. Left-sided BC patients received a significantly higher MHD of 10.5 ± 4.37 Gy. The LAD mean dose was 16.12 ± 15.19 Gy for the entire cohort, increasing to 30.17 ± 5.74 Gy in left-sided cases. Patients with higher MHDs were more likely to receive elevated doses to the LMCA and LCx; however, a notable discrepancy was observed in LAD dose correlation. Regression analysis showed that MHD explained only 9.4% of the variance in LAD mean dose compared to 65% for LMCA. Receiver operating characteristic (ROC) analysis identified heart Dmax (43.12 Gy), heart V25 (13%), and LAD mean dose (28.92 Gy) as strong predictors of subclinical cardiotoxicity, whereas MHD was not. CONCLUSION: Our findings confirm that MHD is an inadequate surrogate for predicting the heterogeneous dose distribution among cardiac substructures. Elevated NT-proBNP levels and reduced EF were significantly associated with higher substructure doses, highlighting the need for individualized, substructure-specific dose constraints in RT planning. These findings support the use of advanced cardiac-sparing techniques such as deep inspiration breath-hold (DIBH), intensity-modulated radiotherapy (IMRT), and proton therapy.