Key result
Higher left-sided cardiac radiation doses linked to increased risk of MACE and heart failure.
Why the study?
Cardiovascular toxicity after adjuvant breast cancer radiotherapy remains a concern, with unclear associations between radiation doses to cardiac substructures and long-term cardiovascular events.
Does radiation dose to specific cardiac substructures predict long-term major adverse cardiac events and specific cardiovascular toxicities in women treated with adjuvant breast cancer radiotherapy?
Case-Control (n=878)
Does radiation dose to specific cardiac substructures predict long-term major adverse cardiac events and specific cardiovascular toxicities in women treated with adjuvant breast cancer radiotherapy?
p-value: p=<0.05
Radiation exposure to specific left-sided cardiac substructures (left atrium and left ventricle) better predicts long-term cardiovascular toxicities after breast cancer radiotherapy than overall mean heart dose.
May warrant substructure dose constraints in breast radiotherapy planning; leaves open prospective confirmation before changing practice.
Background Adjuvant breast cancer (BC) radiotherapy (RT) improves survival and local control, but cardiovascular (CV) toxicity remains a concern. Aim This retrospective study investigated the association between RT doses to cardiac substructures and CV toxicity 15 years after BC RT. Methods Women with unilateral BC diagnosed between 2007 and 2008, treated with RT at [Anonymous] were retrospectively included. Patients with major adverse cardiac events (MACE) were matched to controls by CV risk factors, anthracycline and anti-HER2 therapy. Cardiac substructures were delineated on simulation scans, and multivariable logistic regression was performed to assess associations between RT doses to these substructures and MACE or other CV events. Results After a median follow-up of 16.5 years (IQR 16.1–17.1), and inclusion of 878 patients, 173 patients experienced MACE and were matched to 167 controls. All patients underwent adjuvant RT using 3-dimensional conformal RT to a total dose of 50 Gy in 25 fractions, with or without a boost to the tumor bed. New individual cardiac toxicities included: atrial fibrillation (AF) 98/878 (11.16%), heart failure (HF) 82/878 (9.34%), coronary artery disease (CAD) 46/878 (5.24%) and valvular disease 180/878 (20.50%). Mean heart doses were 6.62 ± 5.20Gy (MACE) and 5.76 ± 4.96Gy (controls) ( p = 0.0916). Compared with controls, patients with MACE had significantly higher disease stage and more frequent histories of CAD, AF and HF. Maximum RT doses to the left atrium (LA) were associated with MACE, new-onset HF, AF and valvular disease, while mean RT dose to the left ventricle (LV) was associated with development of CAD (all p < 0.05). Conclusion This study demonstrates that patients treated with RT for BC may experience diverse CV toxicities during long-term follow-up. Higher doses to left-sided cardiac substructures, particularly the LA and LV, were associated with specific CV endpoints, while MHD was not associated with toxicity.
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Vorst et al. (2026) conducted a case-control in Unilateral breast cancer (n=878). Radiotherapy dose to cardiac substructures (left atrium and left ventricle) vs. Lower radiotherapy doses / Controls was evaluated on Major adverse cardiac events (MACE) and other cardiovascular events (AF, HF, CAD, valvular disease) (p=<0.05). Higher radiotherapy doses to left-sided cardiac substructures (left atrium and left ventricle) were significantly associated with MACE, heart failure, atrial fibrillation, and CAD (all p<0.05).
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