Randomized Double-Blind Placebo-Controlled Trial of Bevacizumab Therapy for Radiation Necrosis of the Central Nervous System

Abstract

Purpose To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials Fourteen patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system (CNS) radiation necrosis. All patients were required to have radiographic or biopsy proof of CNS radiation necrosis and progressive neurological symptoms or signs. Eligible patients received irradiation for head and neck carcinomas, meningioma, or low- to mid-grade gliomas. Patients were randomized to receive IV saline or bevacizumab at 3-week intervals. MRI 3-weeks after the second treatment and clinical signs and symptoms defined response or progression. Results The volumes of necrosis estimated on T2FLAIR and T1-weighted gadolinium-enhanced MRI demonstrated that, while no patient receiving placebo responded (0/7), all bevacizumab-treated patients did (5/5 randomized and 7/7 cross-over) with decreases in T2FLAIR and T1-weighted gadolinium-enhanced volumes and decrease Ktrans. All bevacizumab-treated patients – and none of the placebo-treated patients - showed improvement in neurological symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all 4 study doses, only 2 patients had experienced a recurrence of MRI changes consistent with progressive radiation necrosis, and this was the only patient to receive only 2 treatments with bevacizumab. Conclusions This class I evidence of bevacizumab efficacy in the treatment of CNS radiation necrosis justifies consideration of this treatment option for people who suffer radiation necrosis secondary to the treatment of head and neck and brain cancers.