The Ohio State University Wexner Medical Center Columbus, OH
T. Busby1, M. McCrohan1,2, P. Patel1,2, A. Holtman3, A. Siefker3, E. Wade3, N. Jin4, R. E. Merritt5, D. Diaz3, S. Ghazi1, M. Ferdousi1, P. Ruz1, E. D. Miller3, and D. Addison1,6; 1Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, OH, 2Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, 3Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 4Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 5Division of Thoracic Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 6Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH
Purpose/Objective(s):Radiation therapy (RT) is associated with significant efficacy in the treatment of thoracic malignancies. Yet, it has been linked with potentially limiting cardiotoxicity, including anecdotal reports of profound hypertension (HTN) which may cause additional morbidity. Yet, the long-term incidence, and implications of HTN development in patients requiring thoracic RT are unknown.Materials/
Methods: From a large cohort of consecutive patients with esophageal cancer treated with thoracic RT at a comprehensive cancer center from 2007 to 2019, we assessed the incidence and outcomes of new/incident or worsened HTN [systolic blood pressure (SBP) cutoff, 130 mmHg, based on AHA definitions]. New HTN was defined as elevated SBP post RT initiation on 2 consecutive outpatient visits 3 months apart or initiation of antihypertensive therapy; and worsened HTN as an increase in grade by Common Terminology Criteria for Adverse Events v5.0 or increase in antihypertensive therapy. Secondary outcomes included major adverse cardiovascular events (MACE), defined as arrhythmia, heart failure, myocardial infarction, stroke, and sudden death; as well as overall survival, by HTN status. Landmark analyses, excluding patients with elevated SBPs within 3 months prior to RT (undiagnosed HTN); and those treated with surgery were performed. Multivariate regression was used to define the relation between clinical and RT measures, and outcomes. Further, we assessed the effect of thoracic aorta RT dose on post-RT outcomes. Results: Overall, 238 RT treated patients (82.8% male; median age 63) were identified. Most patients had lower esophageal/gastroesophageal junction (GEJ) tumors (86.9%), T3-4 (78.2%), node positive disease (67.2%), and adenocarcinoma diagnosis (83.6%).Over a median follow-up of 33 months, 55.9% developed new or worsened HTN (median time to HTN, 4 months; median SBP increase 8.9 mmHg). Cumulative incidence of new or worsened HTN by 1 year was 28.8%, and 52.1%, respectively. In landmark analysis, excluding those with undiagnosed HTN, the cumulative incidence of new or worsened HTN was 29.1%, and 45.8%, respectively, by 1 year. On multivariate analysis, only higher disease stage and IMRT-use associated with incident HTN development (P<0.05). Aorta V5 RT-dose trended toward association with incident HTN (P=0.06). Whole heart (V5, V10), left atrium (V5, V10, V15, V20), age, and lower use of IMRT were most consistently associated with MACE (P<0.05 for all). In multivariate models, outside of traditional factors, incident HTN remained associated with improved overall survival (HR: 0.48, P<0.001). This relation remained even after accounting for surgical resection and disease related factors. Conclusion: Among patients with esophageal cancer, RT increases HTN risk even within 1-year of treatment. The development of HTN appears to confer a protective effect on long-term survival.
