The Safety and Efficacy of Bevacizumab for Radiosurgery - Induced Steroid - Resistant Brain Edema; Not the Last Part in the Ship of Theseus.

Background: Radiation-induced brain edema (RIBE) is a serious complication of radiation therapy. It may result in dramatic clinico-radiological deterioration. At present, there are no definite guidelines for management of the complication. Corticosteroids are the usual first line of treatment, which frequently fails to provide long-term efficacy in view of its adverse complication profile. Bevacizumab has been reported to show improvement in cases of steroid-resistant radiation injury. The objective of this study is to evaluate the role of Bevacizumab in post-radiosurgery RIBE.

Material and Methods: Since 2012, 189 out of 1241 patients who underwent radiosurgery at our institution developed post-radiosurgery RIBE, 17 of which did not respond to high-dose corticosteroids. We systematically reviewed these 17 patients of various intracranial pathologies with clinic-radiological evidence of RIBE following gamma knife radiosurgery (GKRS). All patients received protocol-based Bevacizumab therapy. The peer-reviewed literature was evaluated.

Results: 82 percent of the patients showed improvement after starting Bevacizumab. The majority began to improve after the third cycle started improvement after the third cycle of Bevacizumab. Clinical improvement preceded radiological improvement by an average of eight weeks. The first dose was 5 mg/kg followed by 7.5-10 mg/kg at with two-week intervals. Bevacizumab needs to be administered for an average of seven cycles (range 5-27, median 7) for best response. Steroid therapy could be tapered in most patients by the first follow-up. One patient did not respond to Bevacizumab and needed surgical decompression for palliative care. One noncompliant patient died due to radiation injury.

Conclusion: Bevacizumab is a effective and safe for treatment of RIBE after GKRS. A protocol-based dose schedule in addition to frequent clinical and radiological evaluations are required. Bevacizumab should be considered as an early treatment option for RIBE.