title: Bevacizumab for the Treatment of Radiation-Induced Cerebral Necrosis: A Systematic Review of the Literature.
abstract: Radiation necrosis (RN) of brain tissue is a serious late complication of brain irradiation and recently bevacizumab has been suggested as treatment option of RN. There is a lack of data in the literature regarding the effectiveness of bevacizumab for the treatment of RN. The purpose of this review was to perform a comprehensive analysis of all reported cases using bevacizumab for the treatment of brain RN. In September 2016, we performed a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane Library. The research for the review was conducted using a combination of the keywords "radiation necrosis", "radiotherapy" and "bevacizumab" alongside the fields comprising article title, abstract and keywords. Randomized trials, non-randomized trials, prospective studies, retrospective studies and single case reports were included in the review. Our research generated 21 studies and 125 cases where bevacizumab had been used for the treatment of RN. The median follow-up was 8 months and the most frequent bevacizumab dose used was 7.5 mg/kg for 2 weeks with a median of four cycles. Low-dose bevacizumab resulted in effectiveness with improvement in both clinical and radiographic response. The median decrease in T1 contrast enhancement and in T2/FLAIR signal abnormality was 64% and 60%, respectively. A reduction in steroidal therapy was observed in majority of patients treated. Based on the data of our review, bevacizumab appears to be a promising agent for the treatment of brain RN. Future prospective studies are required to evaluate the role of bevacizumab in RN and to define the optimal scheduling, dosage and duration of therapy.
authors.affiliation: Department of Radiotherapy, University Hospital of Pisa, Italy.
authors.forename: Durim
authors.initials: D
authors.lastname: Delishaj
authors.affiliation: Department of Radiotherapy, University Hospital of Pisa, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ursino
authors.affiliation: Department of Radiotherapy, University Hospital of Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pasqualetti
authors.affiliation: Department of Radiotherapy, University Hospital of Pisa, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Cristaudo
authors.affiliation: Neuroradiology Unit, University Hospital of Pisa, Italy.
authors.forename: Mirco
authors.initials: M
authors.lastname: Cosottini
authors.affiliation: Department of Radiotherapy, University Hospital of Pisa, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Fabrini
authors.affiliation: Department of Radiotherapy, University Hospital of Pisa, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Paiar
keywords: Bevacizumab; Brain irradiation; Brain metastases; Stereotactic radiotherapy