The Safety and Efficacy of Bevacizumab for Radiosurgery - Induced Steroid - Resistant Brain Edema; Not the Last Part in the Ship of Theseus

Tripathi, Manjul; Ahuja, Chirag; Mukherjee, Kanchan; Kumar, Narendra; Dhandapani, Sivashanmugam; Dutta, Pinaki; Kaur, Rupinder; Rekhapalli, Rajashekhar; Batish, Aman; Gurnani, Jenil; Kamboj, Parwinder; Agrahari, Abhinav; Kataria, Ketan

doi:10.4103/0028-3886.271242

Cited by 19 publications

(18 citation statements)

References 34 publications

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“…A previous systematic review recommended an initial dose of 7.5 mg/kg every 2 weeks for four cycles to treat patients with RBN (15). Tripathi et al suggested that, to achieve the best response, an average of seven cycles (range: 5-27) of bevacizumab should be administered (61). Our study also indicated that bevacizumab should be administered for up to seven cycles on average (Table 1) (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33).…”

Section: Discussionsupporting

confidence: 59%

“…Although the literature is limited in this regard, several case reports and case series have yielded similar efficacy data (12)(13)(14)(15)(16)(17)(18)(19)(59)(60)(61). One systematic review assessed 16 studies, including seven single-case reports and a total of 71 unique RBN cases reported between 2007 and 2012.…”

Section: Discussionmentioning

confidence: 99%

“…A case report of two melanoma patients with brain metastasis and symptomatic RBN showed clinical improvement and discontinuation of dexamethasone after initial doses of 5 mg/kg every 2 weeks ( 18 ). Bevacizumab has also shown responses in patients with steroid-refractory RBN ( 16 , 17 , 60 , 61 ). A case series of four patients with high-grade glioma, who had developed cerebral edema due to tumor progression or radiation necrosis and were either not responding to corticosteroids or were not candidates for surgical debulking, showed rapid responses to bevacizumab treatment ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

“…Radiographic changes were observed on both T1 and T2 MRI images in all four patients, and three of them also showed a reduction in dexamethasone use ( 17 ). Similarly, in a retrospective study, bevacizumab was administered to 17 patients with radiation-induced brain edema refractory to steroids ( 61 ). The bevacizumab was administered at an increasing dose every 2 weeks (5–7.5–10 mg/kg).…”

Section: Discussionmentioning

confidence: 99%

“…The bevacizumab was administered at an increasing dose every 2 weeks (5–7.5–10 mg/kg). Approximately 82% of the patients showed clinical improvement, and the majority showed improvement after the third dose ( 61 ). In our systematic review, some patients did not show any clinical improvement or experienced symptomatic worsening and progression.…”

Section: Discussionmentioning

confidence: 99%

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Bevacizumab Treatment of Radiation-Induced Brain Necrosis: A Systematic Review

et al. 2021

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BackgroundRadiation brain necrosis (RBN) is a serious complication in patients receiving radiotherapy for intracranial disease. Many studies have investigated the efficacy and safety of bevacizumab in patients with RBN. In the present study, we systematically reviewed the medical literature for studies reporting the efficacy and safety of bevacizumab, as well as for studies comparing bevacizumab with corticosteroids.Materials and MethodsWe searched PubMed, Cochrane library, EMBASE, and ClinicalTrials.gov from their inception through 1 March, 2020 for studies that evaluated the efficacy and safety of bevacizumab in patients with RBN. Two investigators independently performed the study selection, data extraction, and data synthesis.ResultsOverall, the present systematic review included 12 studies (eight retrospective, two prospective, and two randomized control trials [RCTs]) involving 236 patients with RBN treated who were treated with bevacizumab. The two RCTs also had control arms comprising patients with RBN who were treated with corticosteroids/placebo (n=57). Radiographic responses were recorded in 84.7% (200/236) of patients, and radiographic progression was observed in 15.3% (36/236). Clinical improvement was observed in 91% (n=127) of responding patients among seven studies (n=113). All 12 studies reported volume reduction on T1 gadolinium enhancement MRI (median: 50%, range: 26%–80%) and/or T2 FLAIR MRI images (median: 59%, range: 48%–74%). In total, 46 responding patients (34%) had recurrence. The two RCTs revealed significantly improved radiographic response in patients treated with bevacizumab (Levin et al.: p = 0.0013; Xu et al.: p < 0.001). Both also showed clinical improvement (Levin et al.: NA; Xu et al.: p = 0.039) and significant reduction in edema volume on both T1 gadolinium enhancement MRI (Levin et al.: p=0.0058; Xu et al.: p=0.027) and T2 FLAIR MRI (Levin et al.: p=0.0149; Xu et al.: p < 0.001). Neurocognitive improvement was significantly better after 2 months of treatment in patients receiving bevacizumab than in those given corticosteroids, as assessed by the MoCA scale (p = 0.028). The recurrence rate and side effects of the treatments showed no significant differences.ConclusionsPatients with RBN respond to bevacizumab, which can improve clinical outcomes and cognitive function. Bevacizumab appears to be more efficacious than corticosteroid-based treatment. The safety profile was comparable to that of the corticosteroids.

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