脳放射線壊死の成因と治療 : 高度医療(第3項先進医療)の申請 [in Japanese] Pathogenesis and Treatment of Radiation Necrosis in the Brain : Application of Investigational Medical Care System approved by Ministry of Health, Welfare and Labor [in Japanese]
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Symptomatic radiation necrosis is a serious problem after high-dose irradiation for brain tumors. We studied the pathogenesis of radiation necrosis in 18 surgically excised specimens obtained at Osaka Medical College by Hematoxylin and Eosin (H&E) staining and immunohistochemistry. H&E staining showed marked angiogenesis, telangiectasia at the boundary between the necrotic core and normal brain tissue, the so-called peri-necrotic area. Reactive astrocytosis at the peri-necrotic area produced Vascular Endothelial Growth Factor (VEGF) abundantly. These findings are irrespective of original tumor types and radiation modalities. Therefore, we demonstrated the crucial role of VEGF in the pathogenesis of radiation necrosis. Thereafter, we reported the potent effects of bevacizumab, an anti-VEGF antibody, for the treatment of symptomatic radiation necrosis. In a single-institute clinical trial, we applied intravenous administration of bevacizumab to 12 consecutive cases of symptomatic radiation necrosis in the brain. All cases responded well to this treatment, with marked shrinkage of peri-lesional edema. These treatments were effective irrespective of the original tumor types and radiation modalities. Based on these observations, we applied for an Investigational Medical Care System Grant from the Ministry of Health, Labor, and Welfare (MHLW) to study "Intravenous administration of bevacizumab for the treatment of symptomatic radiation necrosis in the brain with the diagnosis based on amino acid PET". MHLW approved the grant on April 1, 2011, and the clinical trial is ongoing. Five institutes are now included in the study, and other several institutes will join it this year for a nationwide multi-institutional clinical trial. The final goal of this clinical trial is to determine the on-label use of bevacizumab for the treatment of symptomatic radiation necrosis in the brain.
- Japanese Journal of Neurosurgery
Japanese Journal of Neurosurgery 21(6), 472-480, 2012
The Japanese Congress of Neurological Surgeons