Left Anterior Descending Artery Dose Predicts Cardiac Risk Better Than Whole-Heart Metrics in Breast Radiotherapy: JAMA

The cross-sectional design entailed the use of very detailed radiation therapy data for the patients followed up over time, involving statistical modeling and data processing performed between September 2024 and April 2026. Specifically, the patient group involved people who received either 3-dimensional conformal or intensity-modulated radiotherapy and among these, only those with left-sided breast cancer underwent primary-risk assessment. Radiation therapy planning doses were derived from the historical computed tomography data by employing sophisticated segmentation techniques and then the data obtained were carefully transformed to the standardized equivalent dose in 2-Gy fractions (EQD2).

Adverse cardiac events including myocardial infarction, unstable angina, acute coronary syndrome, arrhythmias, heart failure, pericarditis, myocarditis, as well as coronary angiography or revascularization procedures, comprised the primary endpoints assessed. The team used receiver operator characteristic curves and competing-risks regression models adjusted by Fine and Gray in their analyses.

Key findings:

• The comprehensive radiation tracking study was conducted on an extensive baseline patient population of 4,908 total patients having breast cancer of which 2,223 subjects had left-sided breast cancer.
• The median follow-up period was long with substantial duration of 10.8 years and an interquartile range ranging from 8.4 to 13.1 years.
• By the time of 10-year post treatment, the cumulative incidence rate of major adverse cardiac event or confirmed coronary artery disease was recorded as precisely 5.0% (95% CI, 4.1-6.0).
• In left-sided breast cancer patients, the maximum LAD dose was shown to have much better discriminatory power as compared to the mean heart dose, giving a concordance index of 0.58 (95% CI, 0.52-0.64) while the concordance index in case of the latter was low and showed 0.53 (95% CI, 0.47-0.60).
• After multivariable adjustment for baseline cardiovascular risk factors, a maximum LAD dose of 12 Gy EQD2 or higher was identified as an independent predictor of heart disease with a subdistribution hazard ratio of 1.81 (95% CI, 1.04-3.16; P = .04).
• Contrary to vessel parameters, there was absolutely no statistical significance in mean whole heart dose of 2 Gy or more in predicting cardiac events (P = .99).
• For immediate real-world use, the 12-Gy EQD2 safety limit translates to a physical dose of approximately 10.5 Gy for a standard 42.5 Gy regimen delivered in 16 fractions, and 7 Gy for an ultra-hypofractionated 26 Gy regimen delivered in 5 fractions.

Overall, in the current cross-sectional study on heart-sparing breast radiotherapy, there is an association between LAD doses and cardiac adverse events, but not with metrics of whole-heart doses. These results suggest that it would be beneficial to implement LAD-based planning and account for respiratory motion in breast cancer patients during radiation therapy to prevent long-term cardiovascular complications. The above-mentioned empirical results represent an essential cornerstone of contemporary precision oncology and clearly demonstrate that survivorship care cannot rely anymore on general organ at risk statistics.

Reference:

Quirk S, Atkins KM, Logie N, et al. Cardiac Risk After Heart-Sparing Breast Radiotherapy. JAMA Oncol. Published online July 02, 2026. doi:10.1001/jamaoncol.2026.2066