A Canadian cross-sectional study suggests looking at whole-heart radiation exposure is not the best predictor of future cardiac risk in breast cancer patients.
The amount of radiation that the left anterior descending coronary artery is exposed to during radiotherapy in breast cancer is a better predictor of future cardiac risk than the whole-heart dose, according to a recent Canadian study.
The new research, published in JAMA Oncology, was a cross-sectional study of 4908 women with breast cancer who underwent radiation therapy at a tertiary care centre in southern Alberta, Canada between 2008 and 2018. The median age was 59.6 years, and the median follow-up was 10.5 years. Less than half of the sample (2223, 45.3%) had left-sided breast cancer, with this subgroup of patients having a median age of 59.9 years and a median follow-up of 10.8 years.
Across the whole sample, 100 patients (2.8%) went on to develop coronary artery disease while 180 (3.7%) experienced an adverse cardiac event (a composite outcome covering myocardial infarctions, hospital admissions or emergency department presentations for unstable angina, heart failure, arrhythmia, pericarditis, or myocarditis). There were 225 patients (4.6%) who had one or both CAD or an adverse cardiac event. Within the left-sided breast cancer subgroup, 115 patients (5.2%) had both CAD and an adverse cardiac event.
A discriminative performance analysis of different dose metrics’ ability to predict cardiac events in patients with left-sided breast cancer found that a maximum left anterior descending coronary artery (LAD) dose of 12Gy was the most discriminative (concordance index 0.58, 95% confidence interval 0.53-0.63). The 12Gy dose was selected for subsequent regression modelling exploring the association between radiation dose and future cardiac events.
After accounting for the influence of patient age, pre-existing medical factors (e.g., hypertension, diabetes, and chronic kidney disease), and radiotherapy treatment factors, patients with left-sided breast cancer who received ≥12Gy of radiation to their LAD were 81% more likely to experience a cardiac future cardiac event (subdistribution hazard ratio 1.81, 95% CI 1.04-3.16) compared to patients who received <12Gy to their LAD. In contrast, there was no association between patients who received a mean heart dose of radiation (≥2Gy versus <2Gy) and cardiac risk (0.90, 0.41-2.01).
“The characterisation of patients by any of the radiotherapy treatment factors was not significant in multivariable models, reinforcing that cardiac risk is more directly captured by dose metrics than by treatment-related surrogates,” the researchers noted.
The research was limited by the fact that data relating to tumour stage and systemic therapy details were not available, meaning these important clinical factors could not be included in the analyses.
“Prior studies have established a dose-response relationship indicating that radiation dose to the heart during breast radiotherapy is associated with an increased risk of major adverse cardiac events (MACEs),” wrote the researchers.
“Although these studies largely evaluated cardiac doses that were considerably higher than doses reported by modern radiotherapy techniques, they continue to influence survivorship care expectations for patients undergoing modern breast radiotherapy.
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“Recent evidence suggests that radiation dose to specific cardiac substructures, especially the LAD, correlates more strongly with predicting cardiac outcomes or that the whole-heart dose is an inadequate predictor altogether.
“In this cross-sectional population-based cohort study of patients with breast cancer and individual coronary dosimetry, the maximum dose to the LAD was independently associated with the risk of adverse cardiac events, whereas whole-heart metrics were not. This indicates that the traditional reliance on whole-heart metrics may obscure clinically relevant injury patterns.
“The implications of this work for clinicians reinforce the value of conscientious LAD sparing in breast radiotherapy, even for patients with satisfactory traditional whole-heart dosimetry.”
