Presenter(s)
K. M. Atkins1, V. Prudente2, S. Bernatz2, L. L. Thompson3, H. Aerts3, and R. H. Mak3; 1Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, 2Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 3Department of Radiation Oncology, Mass General Brigham/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
Purpose/Objective(s): The thymus is a key regulator of immune aging and adaptive immune function, pathways increasingly implicated in cardiovascular disease and cardiometabolic risk. Radiation exposure can degrade thymic health in a dose-dependent manner and influence clinical outcomes. Accordingly, we investigated thymic health as a novel biomarker of cardiovascular risk following cancer therapy using a validated deep learning-based measure.
Materials/Methods: Retrospective analysis of 696 patients with locally advanced non-small cell lung cancer treated with radiotherapy (RT) from 2003-2014. Baseline thymic function was determined from RT simulation CT scans using a validated deep-learning system that auto-segmented the thymus and evaluated its radiographic characteristics as a proxy for thymic functionality. A thymic health score was assigned (range 0-1; higher scores = better function), adjusted for inflammation by expert radiologist review. Preserved thymic health was defined as the upper quartile of thymic score. Fine-Gray regression models predicting major adverse cardiac events (MACE), adjusting for non-cardiac death as a competing risk, were performed. Radiation dose to the left anterior descending coronary artery (LAD), including the volume receiving 15 Gy (V15), and mean thymic dose were extracted from RT plans, and evaluated for interaction with thymic health.
Results: The median follow-up was 5.2 years (interquartile range, 3.4-7.8). Patients with intact thymic health were younger, more often female, and had lower prevalence of diabetes, hyperlipidemia, atherosclerotic cardiovascular disease, and coronary artery calcium (all p<0.05). There was a significant interaction between LAD dose and thymic dose (p=0.045), and a borderline interaction with thymic health (p=0.050). In models adjusting for baseline cardiovascular risk, LAD V15 =10% (vs <10%) remained associated with increased MACE risk when thymic health was impaired at baseline (subdistribution hazard ratio [sHR] 3.28, 95% confidence interval [CI] 1.67-6.57; p=0.001) or impacted by high thymic dose exposure (>median, 49 Gy; sHR 9.08, 95% CI 2.20-37.45; p=0.002), but not when thymic health was intact or thymic dose was low (both p>0.05).
Conclusion: Impaired thymic function, whether at baseline or radiation-related, modifies the association between LAD radiation exposure and major adverse cardiac events, supporting a novel immune-cardiovascular axis in which immune dysregulation may contribute to coronary injury patterns. Thymic health may therefore represent a biomarker and modifiable risk factor for cardiovascular events after thoracic radiotherapy. These findings suggest that thymus-sparing strategies and immune-targeted interventions warrant investigation to mitigate cardiovascular risk after thoracic radiotherapy.