PCSM-04A PROSPECTIVE MULTICENTER SINGLE-ARM CLINICAL TRIAL OF BEVACIZUMAB FOR PATIENTS WITH SURGICALLY UNTREATABLE SYMPTOMATIC BRAIN RADIATION NECROSIS

Abstract

PURPOSE: Brain radiation necrosis (BRN) is a serious adverse event of radiotherapy especially for malignant brain tumors such as glioma and cancer metastasis, which can deteriorate the quality of life in the patients. Since vascular endothelial growth factor is a forcible vascular permeability factor highly expressed in BRN, bevacizumab is expected be an alternative treatment to reduce its perilesional edema. We performed a prospective, multicenter, single-arm trial involving patients with symptomatic BRN to evaluate the safety and efficacy of bevacizumab. PATIENTS AND METHODS: Patients with surgically untreatable symptomatic BRN refractory to conventional treatments (e.g. corticosteroid, anti-coagulants, or hyperbaric oxygen therapy) were enrolled. We judged that a major cause of perilisional edema was BRN, not tumor recurrence, when lesion/normal brain ratio showed ≤ 1.8 or ≤ 2.5 on 11C-methionine and 18 F-boronophenylalanine positron emission tomography (PET), respectively. 5mg/kg of bevacizumab was administrated 6 cycles biweekly. ≥30% reduction of perilesional edema lasting at least one month was specified as the primary endpoint. RESULTS: Forty-one patients were enrolled in this trial. The primary endpoint was achieved in 30 out of 38 (78.9%) patients at 3.03 months (median) after enrollment. Sixteen patients (42.1%) experienced improvement of Karnofsky performance status. Corticosteroid could be reduced in 29 patients (76.3%). Adverse events with grade ≥3 occurred in 10 patients (24.4%). CONCLUSION: Bevacizumab treatment offers certain clinical benefits for patients with surgically untreatable symptomatic BRN. The determination using amino acid PET, not biopsy, is valid and less invasive for eligibility to administrate bevacizumab.