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Association of Pulmonary Artery Radiation with Pulmonary Hypertension after Lung Cancer Radiotherapy
28 Pages Posted: 2 May 2025
More...Abstract
Background: Thoracic radiotherapy results in pulmonary fibrosis that previously was hypothesized to increase the risk of pulmonary hypertension (PH), however dose effects to cardiopulmonary structures predicting PH has not been systematically studied.
Methods: Multi-institutional retrospective cohort analysis of patients with non-small cell lung cancer (NSCLC) treated with thoracic RT. Radiotherapy dose to the pulmonary arteries (PA), distal pulmonary vasculature, lungs, and heart was extracted. Area under the receiver operating curve (AUROC) analyses estimating PH and Fine-Gray regressions were performed.
Findings: Of 848 patients included (n=746 discovery; n=102 validation), 49·9% were women and the median age was 65 years (interquartile range, 58-73 years). The 2-year cumulative incidence of PH was 11·6%. PA volume (V) receiving 10 Gy demonstrated the highest AUROC for predicting PH (0.58), and was significantly associated with the risk of PH on multivariable regression adjusting for cardiopulmonary risk factors in the discovery (subdistribution hazard ratio [sHR] 1·01; 95% CI, 1·00-1·02; p=0·025) and validation (sHR 1·03, 95% CI: 1·00-1·05; p=0·019) cohorts. In those who developed PH after RT (vs PH negative), right ventricular systolic dysfunction (RVSD) and tricuspid disease were more common (4·1% vs 0·5% [p=0·004] and 3·3% vs 0·2% [p=0·003], respectively).
Interpretation: PH was common following thoracic RT and associated with PA radiation dose. After PH, patients were more likely to develop RVSD and tricuspid disease. These findings suggest PH following thoracic RT may occur through a pathophysiological process distinct from RT-induced pulmonary fibrosis and warrants further study.
Keywords: Lung cancer, radiotherapy, pulmonary hypertension, pulmonary artery
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