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Neurooncol Pract. 2016 Dec;3(4):272-280. Epub 2016 Jan 7.

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

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Department of Neurosurgery , Osaka Medical College , Takatsuki, Osaka , Japan (M.F., N.N., T.K., S.-I.M.); Department of Neurosurgery , Kyoto University Graduate School of Medicine , Kyoto , Japan (S.M., Y.A.); Department of Neurosurgery, Chubu Medical Center for Prolonged Traumatic Brain Dysfunction , Kizawa Memorial Hospital , Minokamo , Japan (J.S., K.M.); Division of Neurological Surgery , Chiba Cancer Center , Chiba , Japan (T.I.); Proton Medical Research Center , University of Tsukuba , Tsukuba , Japan (K.T.); Department of Neurosurgery , Hokkaido University Graduate School of Medicine , Sapporo , Japan (K.H., S.T.); Department of Neurosurgery , Japanese Red Cross Medical Center , Tokyo , Japan (Y.T.); Department of Neurosurgery , Kumamoto University Graduate School of Medical Science , Kumamoto , Japan (H.N.); Department of Neurosurgery , Kyorin University Faculty of Medicine , Mitaka , Japan (M.N.); Department of Clinical Oncology and Neuro-oncology Program , Hiroshima University Hospital , Hiroshima , Japan (K.S.); Department of Neurosurgery , Kurume University School of Medicine , Kurume , Japan (M.T.); Department of Neurosurgery , Oita University Faculty of Medicine , Oita , Japan (T.A.); Department of Neurosurgery and Neuro-Oncology , National Cancer Center Hospital , Tokyo , Japan (Y.N.); Department of Neurosurgery , The University of Tokyo , Tokyo , Japan (N.S., A.M.); Department of Neurosurgery , Iwate Medical University , Morioka , Japan (K.O.); Department of Neurosurgery, Division of Hyperbaric Medicine , Iwate Medical University , Morioka , Japan (T.B.); Department of Neurosurgery , Kitasato University School of Medicine , Sagamihara , Japan (T.Kum); Department of Neurosurgery , Tokyo Medical and Dental University , Tokyo , Japan (T.N.); Department of Neurosurgery , Osaka City University Graduate School of Medicine , Osaka , Japan (N.T.); Translational Research Informatics Center , Foundation for Biomedical Research and Innovation , Kobe , Japan (E.N., S.K., Y.N.).



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.


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 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.


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%).


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.


Bevacizumab; brain radiation necrosis; positron emission tomography; vascular endothelial growth factor

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