A prospective, multicentre, single-arm clinical trial of bevacizumab for patients with surgically untreatable, symptomatic brain radiation necrosis†

Abstract

BackgroundBrain 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.MethodsPatients 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 11C-methionine or ≤2.5 on 18F-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.ResultsOf 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%).ConclusionsBevacizumab 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.

Effect of bevacizumab on brain radiation necrosis in anaplastic lymphoma kinase‐positive lung cancer

“…Therefore, bevacizumab, an anti‐VEGF antibody, is effective against brain radiation necrosis and has shown clinical efficacy. It has been suggested that an anti‐VEGF antibody changes tumour vascular function and tumour uptake of anticancer drugs and improves the delivery and efficacy of chemotherapy . The effectiveness of ALK‐TKI improved by bevacizumab might decrease brain tumour size, which might alter brain radiation necrosis.…”

“…Recent reports have demonstrated the effectiveness of bevacizumab in treating brain radiation necrosis. It improves cerebral oedema, helps reduce the corticosteroid dose, and provides symptomatic relief.…”

Focal radiation necrosis of the brain in patients with melanoma brain metastases treated with pembrolizumab

“…35 A single-arm prospective trial also showed a rapid decrease in perilesional edema after initiation of bevacizumab on MRI imaging. 36 Moreover, Glitza et al 37 reported that bevacizumab was safe in the treatment of RNB in patients with melanoma brain metastases treated with immunotherapy. Several reports have shown an increased median overall survival in patients with MBM treated with RT and ipilimumab.…”

Radiation necrosis following proton therapy successfully treated by low‐dose bevacizumab in a patient with relapsed anaplastic ependymoma

“…Although his symptoms, apart from homonymous hemianopsia (Supplementary Figure S1), returned to normal after administration of increased doses of dexamethasone (6 mg/day), subsequent MRI findings (Figure D) disclosed further deterioration 2 months after RN onset. As the effectiveness of the steroid appeared limited, we commenced 5 mg/kg of bevacizumab every 2 weeks for RN treatment. After six courses of bevacizumab, the RN had remarkably improved, with decreased mass size and swelling (Figures E and 1F).…”

“…Several recent studies have demonstrated the effectiveness of bevacizumab for RN in adults and small numbers of pediatric patients. Our observations supported these reports that bevacizumab was well‐tolerated and rapidly improved RN.…”