A-82 Neurocognitive Improvement after Intra-Arterial Bevacizumab for Steroid-Refractory Radiation Necrosis of the Brain

Objective Evaluate neurocognitive change after single low-dose targeted intra-arterial (IA) bevacizumab in patients with brain radiation necrosis. Methods Phase II, single-arm, prospective trial. 10 adults underwent targeted 2.5 mg/kg IA bevacizumab. Neurocognitive indices (Neuropsychological Assessment Battery® and Wechsler Test of Adult Reading) were measured at baseline and 12-months to document performance in 5 domains: Attention, Language, Learning and Memory, Visuospatial, and Executive Function. Clinical indices also quantified. Data (mean ± SD, 95% confidence interval [CI], Cohen’s d) were analyzed using paired t tests. Null hypothesis rejected for p < 0.05. Results At baseline, Numbers-&-Letters Speed T-score (38.2 ± 10.7) indicated decreased processing speed consistent with sub-cortical pattern of illness. All other baseline neurocognitive indices were within normalized means (image). 12-months post-treatment, Numbers-&-Letters Errors T-score increased by 6.0 ± 4.9 [95%CI 1.9,10.1] (t = 3.464, d = 1.225, p = 0.010). List-Learning List-Long-Delayed-Recall T-score increased by 9.0 ± 5.6 [95% CI 4.3,13.7] (t = 4.520, d = 1.598, p = 0.003) and Design-Construction T-score increased by 3.5 ± 4.1 [95%CI 0.04,7.0] (t = 2.391, d = 0.845, p = 0.048). Volume of radiation necrosis decreased by 74.4 ± 14.7% (t = −3.308, d = 1.169, p = 0.013). Headache decreased by 84.4 ± 18.2% (t = −3.495, d = 1.236, p = 0.010). 0/10 died or exhibited AEs attributed to bevacizumab. 2/10 patients experienced radiation necrosis recurrence at months 10 and 11, respectively. Conclusions Single low-dose intra-arterial targeted bevacizumab led to durable neuropsychological performance increase in memory retrieval and visuospatial ability consistent with improvement in sub-cortical function. To our knowledge this is the first prospective report of this novel approach in adults. Clinical improvements mirrored neuropsychologic improvements. Randomized trials are needed comparing targeted low-dose IA bevacizumab to multi-cycle IV bevacizumab at higher doses to determine which is best alternative in brain radiation necrosis.

Bevacizumab efficacy in treatment of brain radiation necrosis

Radiation therapy (RT) plays an important role in treatment of primary and metastatic CNS tumors and some non-neopiastic conditions (arteriovenous malformations, trigeminal neuralgia). Radiation necrosis (RN) is a common adverse effect of RT. Until recently steroid therapy was used as a main treatment regimen for RN. Mechanisms of RN development are not clear; however, it was shown that vascular endothelial growth factor (VEGF) plays a critical role in its formation. A number of surveys showed efficacy of bevacizumab as an anti-VEGF agent in treatment of RN. Radiation necrosis pathogenesis, diagnostics and treatment are summarized in this review.