2978 - Investigation of Cardiovascular Autonomic Dysfunction Diagnosed by Exercise Stress Testing Among Patients Treated with Thoracic Radiotherapy
Presenter(s)
J. P. Nesseler1, M. Oorloff1, O. Peony1, M. Kamrava1, T. Upadhaya1, I. J. Chetty1, C. Ramin2, A. Nikolova3, R. H. Mak4, and K. M. Atkins1; 1Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, 2Department of Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 3Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, 4Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA
Purpose/Objective(s): Cardiovascular (CV) autonomic dysfunction is a dysregulation of heart rate (HR) and blood pressure associated with decreased quality of life (QOL) and increased risk of CV mortality. Thoracic radiotherapy (RT) can contribute to autonomic dysfunction, but clinical and dosimetric predictive factors are poorly understood, and were studied herein.
Materials/Methods: Retrospective single-institution analysis of adults with cancer treated with thoracic RT between February 2009 and January 2024 who underwent post-RT exercise stress testing. The presence of CV autonomic dysfunction was defined as at least two abnormal results among an elevated resting HR (>80 beats/min), an abnormal HR reserve (<80%), an abnormal HR recovery at 1 min (<12 beats/min), a blunted systolic blood pressure response (<20 mmHg), or an abnormal reserve pulse pressure (<44 mmHg). Whole heart and areas of autonomic innervation (aortic arch and sympathetic trunk) were manually delineated and dosimetric parameters (mean, max, and volume [V] receiving 5, 15, and 30 Gy [cc]) extracted. Fine and Gray regressions were performed (death as a competing risk).
Results: Among adult cancer patients treated with thoracic RT, 165 had stress testing following RT. Most (87%, n=143) were female, with breast cancer (82%, n=136) or lung cancer (7%, n=12). The median age at stress testing was 68 years (IQR 58-75), 49% (n=81) had hypertension, 12% (n=20) diabetes, and 5% (n=13) CV disease (CVD). For treatment, 45% (n=75) received chemotherapy, 13% (n=21) targeted agents, 11% (n=18) HER-2 therapy, and 6% (n=10) immune checkpoint inhibitor (ICI) therapy. Median time from RT to stress test was 27 months (IQR 12-52); the most common indications were atypical chest pain (28%, n=47), dyspnea (27%, n=44), cancer rehabilitation workup (24%, n=39), or asymptomatic CV abnormalities (15%, n=25). There were 31 autonomic dysfunction events, with 2- and 5-year cumulative incidence estimates of 9% and 18%. On multivariable regression adjusting for age and baseline CVD, mean aortic arch dose (subdistribution hazard ratio [sHR] 1.05/Gy, 95% confidence interval [CI] 1.00-1.09; p=0.039) and immunotherapy (sHR 4.39, 95% CI 1.59-12.10; p=0.004) were significantly associated with increased risk of autonomic dysfunction, while mean heart and sympathetic chain dose were not (p>0.05). 3/10 patients treated with ICI experienced grade 2 immune-related adverse events, two of whom developed autonomic dysfunction.
Conclusion: CV autonomic dysfunction was commonly identified from stress testing after thoracic RT. Mean aortic arch radiation exposure and receipt of ICI were significantly associated with the risk of autonomic dysfunction. Given the QOL impact of CV autonomic dysfunction, heightened clinical awareness and improved risk mitigation strategies are warranted.