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Updated: Jul 1, 2026
Voluntary Breath-hold Technique for Reducing Heart Dose in Left Breast Radiotherapy
Published on: July 3, 2014
Cardiac Substructure Dosimetry and Major Adverse Cardiac Events After Breast Radiation Therapy: A 12-Year Cohort
Jeffrey C F Lui1, Jeffrey C H Chan2, James C H Chow2
1Departments of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China; Department of Clinical Oncology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Purpose:
To identify cardiac substructure dosimetric predictors of major adverse cardiac events (MACE) following breast radiation therapy (RT), and to develop a robust normal tissue complication probability (NTCP) model for personalized risk assessment using a cohort with over a decade of follow-up.
Methods And Materials:
This retrospective study included 633 female breast cancer patients receiving postoperative RT (2011-2013) at 2 Hong Kong public hospitals. The heart and 6 cardiac substructures were retrospectively contoured on planning computed tomographies, and dose-volume metrics were extracted and converted to equivalent dose in 2 Gy fractions. The primary endpoint was the first occurrence of MACE (cardiogenic death, myocardial infarction, coronary revascularization, unstable angina, or heart failure). Fine-Gray regression was used to identify predictors of MACE, with noncardiogenic death as the competing event. Based on these predictors, an NTCP model was developed to quantify the 10-year excess MACE risk attributable to radiation. Model performance was evaluated using bootstrap optimism-corrected Harrell's C-index and 10-year time-dependent AUC.
Results:
Over a median follow-up of 11.8 years, 29 patients (4.6%) developed MACE. In multivariable analysis, left anterior descending artery (LAD) V40 in equivalent dose in 2 Gy fractions emerged as the strongest dosimetric predictor (subdistribution hazard ratio, 1.023 per %; P = .010). A threshold of LAD V40 ≥18% identified patients at more than 2-fold increased risk of MACE (subdistribution hazard ratio, 2.333; P = .033). The final NTCP model (incorporating LAD V40, age, and cardiac history) demonstrated excellent discrimination with an optimism-corrected C-index of 0.865. Compared with 3-dimensional conformal RT, volumetric modulated arc therapy replanning of high-risk cases substantially reduced LAD V40, translating to an average 5.7% absolute reduction in projected 10-year excess MACE risk.
Conclusions:
In this multicenter cohort with long-term follow-up, LAD V40 was identified as a superior predictor of MACE compared to whole-heart dosimetry. Pending external validation, the developed NTCP model offers a promising framework for personalized risk stratification to guide the use of cardiac-sparing techniques.
