Rdta-05 Bevacizumab for Radiation-Induced Brain Necrosis: A Systematic Review of Randomized Controlled Trials and Cohort Studies

Abstract Radiation therapy for primary and secondary brain cancers can lead to radiation-induced brain necrosis (RBN) with resultant cognitive decline and reduced quality of life. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A, has shown promise in treating RBN and is widely used off-label, though not formally approved in the U.S or Europe. We conducted a systematic review to assess bevacizumab in RBN. Using medical subject headings for bevacizumab and RBN, we searched PubMed, Embase, Google Scholar, and Cochrane databases. Of 456 screened articles, we only included randomized controlled trials (RCTs) and cohort studies, yielding 5 articles. Levin et al. (2011) compared bevacizumab (n=5) with placebo (n=7). Bevacizumab led to clinical and radiological improvement. Subsequently, all patients in the placebo group crossed over to bevacizumab and demonstrated similarly beneficial results. Sadraei et al. (2015) demonstrated that 23 of 24 patients on bevacizumab had 53.7% decrease in MRI findings and dexamethasone dose, with only 1 grade 3 AE. Xu et al. (2018) conducted an RCT demonstrating superior efficacy of bevacizumab (n=58) over steroids (n=54) in terms of composite radiological and clinical improvement (65.5% vs 31.5% p0.01), decrease in necrosis volume on MRI (51.8% vs 19.3%) and clinical improvement (62.1% vs 42.6%, p=0.039). Voss et al. (2021) analyzed a single dose of bevacizumab in steroid-refractory patients (n=11). All 11 patients demonstrated improved KPS and reduced steroid dose, 9 had 25% reduction in brain edema, 7 had clinical improvement, and 6 discontinued steroids. Dashti et al. (2022) prospectively evaluated single intra-arterial 2.5 mg/kg dose of bevacizumab after blood-brain barrier disruption in 10 steroid-refractory patients. At 12 months, necrosis volume decreased by 74% (p=0.012), edema by 50% (p=0.086), and headaches by 84% (p=0.022); 90% discontinued steroids. To conclude, bevacizumab demonstrates promising efficacy in RBN, warranting further studies for possible FDA approval.