TOPLINE

In a cross-sectional study of patients who received heart-sparing radiotherapy for breast cancer, maximum dose to the left anterior descending (LAD) coronary artery predicted long-term cardiac risk, while mean heart dose did not.

METHODOLOGY

• Recent evidence suggests that radiation dose to specific cardiac substructures, especially the LAD, better predicts cardiac outcomes than whole-heart dose metrics. Yet prospective LAD contouring remains uncommon, and clinically actionable dose objectives have not been established for breast cancer radiotherapy in North America.
• Researchers conducted a cross-sectional study of 4908 patients with breast cancer (2223 with left-sided disease) treated with three-dimensional conformal or intensity-modulated radiotherapy between 2008 and 2018 at a tertiary care center in Calgary, Canada. The deep inspiration breath-hold technique was introduced in 2013 and utilized in 465 patients (21%) with left-sided disease.
• The main outcome was the incidence of cardiac events (myocardial infarction, unstable angina, arrhythmia, heart failure, pericarditis, or myocarditis) or coronary artery disease (documented coronary angiography or revascularization).
• Dosimetry was derived from CT plans using AI-based segmentation, with all radiation doses converted to equivalent dose in 2 Gy fractions (EQD₂) using an alpha/beta ratio of 3 for late cardiac effects. Analyses included receiver operating characteristic curves and competing risks regression, adjusted for cardiovascular risk factors.

TAKEAWAY

• Over a median follow-up of 10.8 years, cumulative incidence of cardiac events or coronary artery disease was 5% among patients with left-sided disease, with a median time to event of 4.5 years.
• A clinically relevant maximum LAD dose of 12 Gy (EQD₂) was identified. Maximum LAD dose (concordance index, 0.58; 95% CI, 0.52-0.64) discriminated cardiac events better than mean heart dose (concordance index, 0.53; 95% CI, 0.47-0.60) in patients with left-sided breast cancer.
• In multivariable analysis, maximum LAD dose ≥ 12 Gy was independently associated with higher cardiac risk (subdistribution hazard ratio, 1.81; P = .04), whereas mean heart dose ≥ 2 Gy showed no association (P = .99).
• Implementation of the deep inspiration breath-hold technique increased the proportion of patients with left-sided breast cancer receiving a maximum LAD dose < 12 Gy from 8.6% to 53.2% (P < .001).

IN PRACTICE

“These findings substantiate the use of LAD dosimetry and strengthen the evidence associating cardiac irradiation with late cardiac morbidity, which supports a shift to including LAD-specific dose objectives in treatment planning,” the study authors wrote. “Incorporating LAD sparing into breast radiotherapy protocols and auditing LAD dose as part of institutional quality assurance may reduce preventable cardiac harms.”

SOURCE

The study, led by Sarah Quirk, PhD, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS

The study lacked data on tumor stage and details on systemic therapies, some of which have cardiotoxicities. The predictive performance of maximum LAD dose (concordance index 0.58) was modest. The study only evaluated cardiac risk with the LAD and whole heart and did not exclude other cardiac substructures previously investigated for association with risk.

DISCLOSURES

Several co-authors reported financial relationships with various pharmaceutical and healthcare companies outside the submitted work. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.