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.

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

“…Recently, a meta‐analysis showed that bevacizumab treatment in patients with RNB leads to a reduction or stabilization of corticosteroid treatment in 97% of patients, and a clinical improvement of the neurological symptoms in 91.2% of patients. There were only 2.4% of grade three adverse events . A single‐arm prospective trial also showed a rapid decrease in perilesional edema after initiation of bevacizumab on MRI imaging .…”

“…There were only 2.4% of grade three adverse events. 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.…”

Modern Ideas About the Combination of Radiation Therapy With Antiangiogenic Drugs in the Treatment of Patients With Brain Metastases

“…Риск кровотечения из ЦНС был основной проблемой при введении антиангиогенной терапии в практику и приводил к частому исключению пациентов с метастазами головного мозга из клинических исследований [16]. Однако в ряде последующих исследований было доказано, что проблема повышенной опасности отсутствует, так как частота кровотечений, а также других побочных эффектов у пациентов с метастазами в головном мозге не увеличивалась [16][17][18][19][20][21][22][23][24][25][26][27][28]. В соответствии с этим частота побочных явлений, связанных с бевацизумабом, была одинаковой у пациентов с (21 %) и без (20 %) метастазов в головной мозг [17].…”

“…Для достижения контроля над симптомами, вызванными отеком, часто необходимы высокие дозы кортикостероидов, применение которых, в свою очередь, сопровождается большим количеством побочных эффектов. Несколько исследований показали, что применение бевацизумаба безопасно у пациентов с возникшим радионекрозом и уменьшает выраженность симптоматики, тем самым улучшая качество жизни [26,27]. Необходимы рандомизированные проспективные исследования для определения оптимального графика, дозировки и продолжительности терапии.…”

Neurologic complications of melanoma

“…Despite retrospective and small prospective studies describing the efficacy of VEGF inhibitors in the setting of radiation necrosis for decreasing edema and associated symptoms, the decision to initiate treatment can be difficult . Levin et al reported that all patients who received bevacizumab for the treatment of radiation necrosis had decreased MRI findings and neurologic symptoms or signs associated with radiation necrosis.…”