Angiotensin receptor blockade: a novel approach for symptomatic radiation necrosis after stereotactic radiosurgery

• Type of Material: Article
• Authors: Mudit Chowdhary, Rush University; Derick Okwan-Duodu, Emory University; Jeffrey M. Switchenko, Emory University; Robert H. Press, Emory University; Jaymin Jhaveri, Emory University; Zachary S. Buchwald, Emory University; Jim Zhong, Emory University; Bhavana V. Chapman, University of Texas MD Anderson Cancer Center; Ranjit S. Bindra, Yale School of Medicine; Joseph N. Contessa, Yale School of Medicine; Henry S. Park, Yale School of Medicine; James B. Yu, Yale School of Medicine; Roy H. Decker, Yale School of Medicine; Jeffrey James Olson, Emory University; Nelson M Oyesiku, Emory University; Ross A. Abrams, Emory University; Hui-Kuo G. Shu, Rush University; Walter J Curran, Emory University; Ian Crocker, Emory University; Kirtesh R. Patel, Yale School of Medicine
• Language: English
• Date: 2018-01-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017, Springer Science+Business Media, LLC.
• Final Published Version (URL): http://dx.doi.org/10.1007/s11060-017-2652-0
• Title of Journal or Parent Work: Journal of Neuro-Oncology
• ISSN: 0167-594X
• Volume: 136
• Issue: 2
• Start Page: 289
• End Page: 298
• Grant/Funding Information: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; Research reported in this publication was supported in part by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292.
• Keywords: THERAPY; Brain metastases; MECHANISMS; Angiotensin converting enzyme inhibitor; WHOLE-BRAIN RADIOTHERAPY; RISK; DIAGNOSIS; Neurosciences & Neurology; Radiation necrosis; Oncology; Life Sciences & Biomedicine; PNEUMONITIS; Arteriovenous malformation; SURGICAL RESECTION; Angiotensin receptor blocker; CONVERTING ENZYME-INHIBITORS; Clinical Neurology; METASTASES; Science & Technology; RANDOMIZED-TRIAL
• Research Categories: Health Sciences, Oncology

Abstract

Preclinical evidence suggests angiotensin blockade therapy (ABT) decreases late radiation toxicities. This study aims to investigate the association between ABT and symptomatic radiation necrosis (SRN) following stereotactic radiosurgery (SRS). Resected brain metastases (rBM) and arteriovenous malformation (AVM) patients treated with SRS from 2002 to 2015 were identified. Patients in the ABT cohort were on therapy during SRS and at 1-mo nth follow up. Kaplan Meier method and cumulative incidence model were used to analyze overall survival (OS) and intracranial outcomes. 228 consecutive patients were treated with SRS: 111 with rBM and 117 with AVM. Overall, 51 (22.4%) patients were in the ABT group: 32 (28.8%) in the rBM and 19 (16.2%) in AVM cohorts. Baseline characteristics were similar, except for higher Graded Prognostic Analysis (3–4) in the rBM (ABT: 25.0% vs. non-ABT: 49.0%, p = 0.033) and median age in the AVM (ABT: 51.4 vs. non-ABT: 35.4, p < 0.001) cohorts. In both populations, OS and intracranial efficacy (rBM—local control; AVM—obliteration rates) were statistically similar between the cohorts. ABT was associated with lower 1-year SRN rates in both populations: rBM, 3.1 versus 25.3% (p = 0.003); AVM, 6.7 vs. 14.6% (p = 0.063). On multivariate analysis, ABT was a significant predictive factor for rBM (HR: 0.17; 95% CI 0.03–0.88, p = 0.035), but did not reach statistical significance for AVM (HR: 0.36; 95% CI 0.09–1.52, p = 0.165). ABT use appears to be associated with a reduced risk of SRN following SRS, without detriment to OS or intracranial efficacy. A prospective trial to validate these findings is warranted.