Predicting Adverse Cardiac Events After Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer.

Background: Radiotherapy may cause grade ≥3 cardiac events, necessitating a better understanding of risk factors. The potential predictive role of imaging biomarkers with radiotherapy doses for cardiac event occurrence has not been studied.
Objectives: The aim of this study was to establish the associations between cardiac substructure dose and coronary artery calcium (CAC) scores and cardiac event occurrence.
Methods: A retrospective cohort analysis included patients with locally advanced non-small cell lung cancer treated with radiotherapy (2006-2018). Cardiac substructures, including the left anterior descending coronary artery, left main coronary artery, left circumflex coronary artery, right coronary artery, and TotalLeft (left anterior descending, left main, and left circumflex coronary arteries), were contoured. Doses were measured in 2-Gy equivalent units, and visual CAC scoring was compared with automated scoring. Grade ≥3 adverse cardiac events were recorded. Time-dependent receiver-operating characteristic modeling, the log-rank statistic, and competing-risk models were used to measure prediction performance, threshold modeling, and the cumulative incidence of cardiac events, respectively.
Results: Of the 233 eligible patients, 61.4% were men, with a median age of 68.1 years (range: 34.9-90.7 years). The median follow-up period was 73.7 months (range: 1.6-153.9 months). Following radiotherapy, 22.3% experienced cardiac events, within a median time of 21.5 months (range: 1.7-118.9 months). Visual CAC scoring showed significant correlation with automated scoring ( r  = 0.72; P  < 0.001). In a competing-risk multivariable model, TotalLeft volume receiving 15 Gy (per 1 cc; HR: 1.38; 95% CI: 1.11-1.72; P  = 0.004) and CAC score >5 (HR: 2.51; 95% CI: 1.08-5.86; P  = 0.033) were independently associated with cardiac events. A model incorporating age, TotalLeft CAC (score >5), and volume receiving 15 Gy demonstrated a higher incidence of cardiac events for a high-risk group (28.9%) compared with a low-risk group (6.9%) ( P  < 0.001).
Conclusions: Adverse cardiac events associated with radiation occur in more than 20% of patients undergoing thoracic radiotherapy within a median time of <2 years. The present findings provide further evidence to support significant associations between TotalLeft radiotherapy dose and cardiac events and define CAC as a predictive risk factor.
Competing Interests: This work was supported by a Radiological Society of North America Research & Education Foundation Resident Research Grant. Dr No has received research grant funding from the Radiological Society of North America. Dr Kastelowitz has received research grant funding from the American Society for Radiation Oncology–LUNGevity and the Radiological Society of North America; and has received consulting fees from MIM Software. Dr Rhee has received funding from the National Institutes of Health (grant K08-HL148540); and has conducted industry-sponsored research for Pfizer. Dr Clark has received research grant funding from the Adult Congenital Heart Association. Dr Vitzthum has received research grants from RefleXion. Dr Loo has received research grants from the National Institutes of Health (grant P01CA244091) and Varian Medical Systems; holds stock in TibaRay; and is a board member for TibaRay. Dr Diehn has received research grant funding from Varian, Genentech, and AstraZeneca; receives royalties for patent licenses from Roche and Foresight Diagnostics; has received consulting fees from Roche, Varian, BioNTech, RefleXion, Novartis, Illumina, Genentech, Boehringer Ingelheim, and Gritstone Oncology; licenses patents to Roche and Foresight Diagnostics for liquid biopsy methods and to Celgene for single-cell analysis methods; is on advisory boards for AstraZeneca, Genentech, Boehringer Ingelheim, Illumina, and Gritstone Oncology; is a board member for Foresight Diagnostics; holds stock in Foresight Diagnostics and CiberMed; and receives in-kind research reagents from Illumina. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(© 2023 The Authors.)