Key result
Cardiac calcification burden and age predict related cardiac events with ~0.80 AUC.
Why the study?
Cardiac calcifications are emerging predictors of cardiotoxicity after breast cancer radiotherapy, but their association with specific subgroups of cardiac events and the interplay with dosimetric and clinical predictors during moderate hypofractionation remained unclear.
Cohort (n=1,091)
No
Effect estimate: AUC 0.80
p-value: p=<0.0001
Cardiac calcification scores strongly predict atherosclerotic-related cardiac events after breast radiotherapy, while non-atherosclerotic events are more related to left-sided irradiation, anthracycline use, and respiratory toxicity.
CAC burden and age predict coronary events while treatment factors predict others after hypofractionated breast RT; leaves open tailored risk stratification.
Background and purpose Cardiac calcifications (CAC) are emerging as relevant predictors of cardiac toxicity after breast cancer radiotherapy. This study aimed to investigate the association between quantitative CAC scores and specific subgroups of cardiac events in patients treated with moderate hypofractionation, and to assess the interplay between dosimetric and clinical predictors for different families of events. Materials and methods Data from 1172 consecutive breast cancer patients treated at a single institution with 40 Gy in 15 fractions were analyzed. Mean heart dose (MHD) was extracted after automatic heart segmentation. Agatston score (AS), CAC volume, and maximum heart HU value (Max_HU) were quantified from planning CT scans. Available clinical variables included laterality, chemotherapy, age, smoking status, and respiratory toxicity occurring within 3 years after radiotherapy. Cardiac events were classified into two groups: CAC_corr (coronary artery disease, acute myocardial infarction, congestive heart failure, and valvular disease) and CAC_uncorr (conduction abnormalities, atrial premature beats, atrial fibrillation, pericarditis, and tachyarrhythmia). Associations between predictors and outcomes were tested using logistic regression. Results After excluding patients with pacemakers/electrodes, 1091 patients were available. With a median follow-up of 6.5 years, 29 cardiac events were recorded. Among them, 15/29 were CAC_corr and were similarly distributed between right-and left-sided tumors (8 vs 7). Conversely, 13/14 CAC_uncorr events occurred in left breast cancer patients; therefore, analyses for this subgroup were restricted to left-sided cases (13/561). For CAC_corr events, the combination of AS/CAC_volume/Max_HU with age showed the best predictive performance (AUC=0.80/0.79, p<0.0001), while respiratory toxicity had no impact. For CAC_uncorr events, age and anthracycline-based chemotherapy (FEC) were the strongest predictors (AUC=0.73, p=0.0125). Including respiratory toxicity significantly improved model performance (AUC=0.77, p=0.0003). MHD was not independently associated with cardiac events. Conclusion CAC_corr events were mainly associated with CAC burden and age, independently of tumor laterality. In contrast, CAC_uncorr events appeared more related to treatment-related factors, as most occurred after left-sided irradiation. Within left breast cancer patients, these events were mainly associated with age, anthracycline-based chemotherapy, and respiratory toxicity rather than with MHD.
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Belardo et al. (2026) conducted a cohort in Breast cancer (n=1,091). Cardiac calcifications (CAC) vs. Lower or absent cardiac calcifications was evaluated on CAC_corr cardiac events (coronary artery disease, acute myocardial infarction, congestive heart failure, and valvular disease) (AUC 0.80, p=<0.0001). Cardiac calcification burden and age strongly predicted calcification-related cardiac events (AUC 0.80), while unrelated events were associated with age, anthracyclines, and respiratory toxicity.
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