Bevacizumab therapy for cerebral radiation necrosisManmeet Ahluwalia1, Neda Hashemi-Sadraei2, Gazanfar Rahmatullah2, John Suh3, Sam Chao2, Robert Weil2, Michael Vogelbaum2, David Peereboom2, Glen Stevens2, Gene Barneet21Cleveland, United States 2Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic 3Taussig Cancer Institute, Cleveland Clinic Keywords: brain tumor, gamma knife, radiation injury, complications, bevacizumabInteractive ManuscriptAsk Questions of this Manuscript: What is the background behind your study?Radiation necrosis is a serious complication of radiation treatment for brain tumors. Therapeutic options including steroids, anticoagulation and hyperbaric oxygen have limited efficacy. Radiation necrosis is postulated to be a continuous process involving endothelial cell dysfunction that leads to tissue hypoxia and necrosis, with secretion of the vascular endothelial growth factor (VEGF). Bevacizumab, an antibody against VEGF had been reported to reduce edema in patients with suspected radiation necrosis. Therapeutic options including steroids, anticoagulation and hyperbaric oxygen have limited efficacy. Radiation necrosis is postulated to be a continuous process involving endothelial cell dysfunction that leads to tissue hypoxia and necrosis, with secretion of the vascular endothelial growth factor (VEGF). What is the purpose of your study?Bevacizumab, an antibody against VEGF had been reported to reduce edema in patients with suspected radiation necrosis. Describe your patient group.19 patients with diagnosis of radiation necrosis (4 were biopsy proven) received bevacizumab. Describe what you did.After obtaining IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify patients with diagnosis of Radiation necrosis on the basis of magnetic resonance imaging (MRI) and/ or biopsy who were treated with bevacizumab between 7/2007 and 1/2011. Describe your main findings.Post treatment MRI was performed at an average of 8 weeks after initiating therapy with bevacizumab. Follow-up MRI demonstrated a radiographic response in all patients on the MRI fluid-attenuated inversion-recovery (FLAIR) sequences and 18 of 19 patients showed improvement in the T1-weighted post-Gadolinium contrast images. The average area change in the T1-weighted post-Gadolinium contrast abnormalities was a decrease of 45.1%, and the average change in the FLAIR images was a decrease of 49.1% (using McDonald’s criteria). Fifteen patients showed clinical benefit. There was a mean daily dose reduction of 5.96 mg of dexamethasone after initiation of bevacizumab in patients who were on steroids at start of bevaciuzmab for radiation necrosis. Describe the main limitation of this study.This was a retrospective review. Describe your main conclusion.Bevacizumab appears to produce radiographic response as well as clinical benefit in the treatment of patients with cerebral radiation necrosis. Describe the importance of your findings and how they can be used by others.The improvements can be rapid and bevacizumab is effective in cases that do not respond to traditional corticosteroid therapy. Radiation necrosis is a serious complication of radiation treatment for brain tumors. Therapeutic options including steroids, anticoagulation and hyperbaric oxygen have limited efficacy. Radiation necrosis is postulated to be a continuous process involving endothelial cell dysfunction that leads to tissue hypoxia and necrosis, with secretion of the vascular endothelial growth factor (VEGF). Bevacizumab, an antibody against VEGF had been reported to reduce edema in patients with suspected radiation necrosis. Therapeutic options including steroids, anticoagulation and hyperbaric oxygen have limited efficacy. Radiation necrosis is postulated to be a continuous process involving endothelial cell dysfunction that leads to tissue hypoxia and necrosis, with secretion of the vascular endothelial growth factor (VEGF).
Bevacizumab, an antibody against VEGF had been reported to reduce edema in patients with suspected radiation necrosis. 19 patients with diagnosis of radiation necrosis (4 were biopsy proven) received bevacizumab. After obtaining IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify patients with diagnosis of Radiation necrosis on the basis of magnetic resonance imaging (MRI) and/ or biopsy who were treated with bevacizumab between 7/2007 and 1/2011. Post treatment MRI was performed at an average of 8 weeks after initiating therapy with bevacizumab. Follow-up MRI demonstrated a radiographic response in all patients on the MRI fluid-attenuated inversion-recovery (FLAIR) sequences and 18 of 19 patients showed improvement in the T1-weighted post-Gadolinium contrast images. The average area change in the T1-weighted post-Gadolinium contrast abnormalities was a decrease of 45.1%, and the average change in the FLAIR images was a decrease of 49.1% (using McDonald’s criteria). Fifteen patients showed clinical benefit. There was a mean daily dose reduction of 5.96 mg of dexamethasone after initiation of bevacizumab in patients who were on steroids at start of bevaciuzmab for radiation necrosis. This was a retrospective review. Bevacizumab appears to produce radiographic response as well as clinical benefit in the treatment of patients with cerebral radiation necrosis.
The improvements can be rapid and bevacizumab is effective in cases that do not respond to traditional corticosteroid therapy. Project Roles:
M. Ahluwalia (), N. Hashemi-Sadraei (), G. Rahmatullah (), J. Suh (), S. Chao (), R. Weil (), M. Vogelbaum (), D. Peereboom (), G. Stevens (), G. Barneet ()
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