Abstract 4144401: Hypertension and Incident Cardiovascular Events following Thoracic Radiotherapy

Introduction: Radiation therapy (RT) is associated with high efficacy in treating thoracic malignancies. However, it has been linked to potentially limiting cardiotoxicity, including anecdotal reports of profound hypertension (HTN). Yet, the long-term incidence and implications of HTN development after RT is unknown. Aims: We aimed to define the relation between RT and HTN development in patients with lung and esophageal cancers, as well as the association of RT with major adverse cardiac event (MACE) and overall survival. Methods: From a large cohort of consecutive esophageal and lung cancer patients treated with thoracic RT from 2007-2019, we assessed the incidence and outcomes of incident (new) or worsened HTN [systolic blood pressure (SBP) ≥130mmHg] after RT initiation. Secondary outcomes were MACE (heart failure, myocardial infarction, stroke, arrhythmia and sudden death) and overall survival by RT dose. Differences in outcomes by HTN status were also evaluated via landmark analysis, excluding those with undiagnosed HTN. Observed new HTN rates were compared to Framingham predicted rates, and absolute excess risks were estimated. Multivariate regression was used to define the relation between clinical and RT measures (including cardiac and aorta substructure dose) and outcomes. Results: Overall, 439 RT-treated patients (238 esophageal; 201 lung; 66.7% male; mean age 63.2 years; 57.9% baseline HTN) were identified. Most (67.4%) had advanced T3-4 disease. Over a median follow-up of 23 months, 262 (59.7%) developed new or worsened HTN; median SBP increase of 8 mmHg. In landmark analysis, the cumulative incidence of new or worsened HTN by 1 year was 48.0% and 68.5%, respectively. Using the JNC 8 cutoff of ≥140/90 mmHg, the new HTN rate was 19.1% at 1 year, translating to a 1.7-fold higher rate than the Framingham predicted rate (RR 1.72, P <0.0001). In multivariate models, RT dose consistently associated with new or worsened HTN development ( P <0.05). Similarly, beyond age, only RT-dose (aorta max dose, mean dose, V60; whole heart, left atrium, left ventricle, right atrium V60; right ventricle max dose, mean dose, V50, V60) consistently associated with MACE ( P <0.05 for all). In multivariate analysis, new HTN remained associated with improved overall survival (HR: 0.75, P <0.001), even after accounting for surgical resection and disease-related factors. Conclusion: In patients with lung and esophageal cancers, RT increases HTN risk even within 1-year of treatment.