Abstract
BACKGROUND: Brain radiation necrosis (BRN) can be a complication of radiotherapy for primary and secondary brain tumors, as well as head and neck tumors. Since vascular endothelial growth factor (VEGF) is also a vascular permeability factor in the brain, bevacizumab, a humanized antibody that inhibits VEGF, would be expected to reduce perilesional edema that often accompanies BRN. METHODS: Patients with surgically untreatable, symptomatic BRN refractory to conventional medical treatments (eg, corticosteroid, anticoagulants, or hyperbaric oxygen therapy) were enrolled. We judged that a major cause of perilesional edema with a lesion-to-normal brain ratio ≤1.8 on (11)C-methionine or ≤2.5 on (18)F-boronophenylalanine PET was BRN, not tumor recurrence, and 6 cycles of biweekly bevacizumab (5 mg/kg) were administered. The primary endpoint was a ≥30% reduction from the patients' registration for perilesional edema continuing for ≥1 month. RESULTS: Of the 41 patients enrolled, 38 were fully eligible for the response assessment. The primary endpoint was achieved in 30 of the 38 (78.9%) patients at 3.0 months (median) after enrollment. Sixteen patients (42.1%) experienced improvement of their Karnofsy Performance Score. Corticosteroid use could be reduced in 29 patients (76.3%). Adverse events at grade ≥3 occurred in 10 patients (24.4%). CONCLUSIONS: Bevacizumab treatment offers certain clinical benefits for patients with surgically untreatable, symptomatic BRN. The determination of BRN using amino-acid PET, not biopsy, is adequate and less invasive for determining eligibility to receive bevacizumab.