International journal of radiation oncology, biology, physics · 2026
Cardiac Substructure Dosimetry and Major Adverse Cardiac Events After Breast Radiation Therapy: A 12-Year Cohort Study With Normal Tissue Complication Probability Modeling.
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Lui Jeffrey C F, Chan Jeffrey C H, Chow James C H, Tong Julian, Lee Jonan C Y, Lee Francis K H, Cheung Gavin T C, Leung Vincent W S, Lee Victor H F, Jimenez Rachel B
Аннотация
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.
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.