In a retrospective cohort analysis reported in JAMA Oncology, Atkins et al identified a volume (V, percent) of exposure of the left anterior descending (LAD) coronary artery to a radiation dose (V15 Gy ≥10%) that is an independent risk factor for major adverse cardiac events and all-cause mortality in patients receiving radiotherapy for locally advanced non–small cell lung cancer (NSCLC).
Study Details
The study involved 701 consecutive patients receiving thoracic radiotherapy for NSCLC at Harvard University–affiliated hospitals between December 2003 and January 2014. Major adverse cardiac events included unstable angina, heart failure hospitalization or urgent visit, myocardial infarction, coronary revascularization, and cardiac death.
“The findings of this cohort study suggest that optimal cardiac dose constraints may differ based on preexisting coronary heart disease.... These constraints are worthy of further study because there is a need for improved cardiac risk stratification and aggressive risk mitigation strategies.”— Atkins et al
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Key Findings
The median follow-up for major adverse cardiac events was 20.4 months (interquartile range [IQR] = 8.2–44.6months) overall and 47.8 months (IQR = 31.6–75.4 months) among surviving patients.
In the total cohort, the optimal cutpoints for delineating risk of major adverse cardiac events (highest C-index value) were LAD coronary artery V15 Gy ≥ 10% (0.64), left circumflex coronary artery V15 Gy ≥ 14% (0.64), left ventricle V15 Gy ≥ 1% (0.64), and mean total coronary artery dose ≥ 7 Gy (0.62).
In analysis adjusting for age, hypertension, diabetes, arrhythmia, coronary heart disease, and radiotherapy technique, LAD coronary artery V15 Gy ≥ 10% was associated with increased risk of major adverse cardiac events (adjusted hazard ratio [HR] = 13.90, 95% CI = 1.23–157.21, P = .03) and all-cause mortality (adjusted HR = 1.58, 95% CI = 1.09–2.29, P = .02).
Among 449 patients without coronary heart disease, increased risk of major adverse cardiac events at 1 year was significantly associated (all P < .001) with LAD coronary artery V15 Gy ≥ 10% (4.9% vs 0% for <10%), left circumflex coronary artery V15 Gy ≥ 14% (5.2% vs 0.7%), left ventricle V15 Gy ≥ 1% (5.0% vs 0.4%), and mean total coronary artery dose ≥ 7 Gy (4.8% vs 0%). Among 252 patients with coronary heart disease, only left ventricle V15 Gy ≥ 1% was associated with increased risk (8.4% vs 4.1%, P = .046).
Among patients without coronary heart disease, 2-year all-cause mortality was increased with LAD coronary artery V15 Gy ≥ 10% (51.2% vs 42.2%, P = .009) and mean total coronary artery dose ≥ 7 Gy (53.2% vs 40.0%, P = .01). Among those with coronary heart disease, no increase in risk was observed for LAD coronary artery V15 Gy ≥ 10% or according to the cutpoints for other cardiac substructures.
The investigators concluded, “The findings of this cohort study suggest that optimal cardiac dose constraints may differ based on preexisting coronary heart disease. Although the LAD coronary artery V15Gy greater than or equal to 10% appeared to be an independent estimator of the probability of major adverse cardiac events and all-cause mortality, particularly in patients without coronary heart disease, left ventricle V15 Gy greater than or equal to 1% appeared to confer an increased risk of major adverse cardiac events among patients with coronary heart disease. These constraints are worthy of further study because there is a need for improved cardiac risk stratification and aggressive risk mitigation strategies.”
Raymond H. Mak, MD, of Dana-Farber Cancer Institute and Brigham and Women's Hospital, is the corresponding author for the JAMA Oncology article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
