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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Abstract

当施設で経験した18例の脳放射線壊死病理組織を検討し,壊死巣周囲に反応性アストロサイトが集簇し,血管内皮増殖因子(VEGF)を産生し,これが脆弱な血管新生を惹起し,そこからの血漿成分の漏出が脳浮腫の原因であることを解明した.そこで,12名の症候性脳放射線壊死の症例に抗VEGF抗体であるベバシズマブの静脈内投与を単一施設の臨床研究として行ったところ,全例で脳浮腫の軽減を認めた.以上の結果に基づき,「脳放射線壊死に対する核医学的診断とベバシズマブの静脈内投与による治療」を高度医療(第3項先進医療)として厚生労働省に申請し,2011年4月1日に認可され,薬事承認を目指した多施設臨床試験として現在実施中である.

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.

Journal

  • Japanese Journal of Neurosurgery

    Japanese Journal of Neurosurgery 21(6), 472-480, 2012

    The Japanese Congress of Neurological Surgeons

References:  15

Cited by:  1

Codes

  • NII Article ID (NAID)
    110009457757
  • NII NACSIS-CAT ID (NCID)
    AN10380506
  • Text Lang
    JPN
  • Article Type
    Journal Article
  • ISSN
    0917-950X
  • Data Source
    CJP  CJPref  NII-ELS  J-STAGE 
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