Neurological Surgery 脳神経外科43巻3号

2015年03月発行

総説

小児脳腫瘍に対する化学療法—治療の進化

著者： 柳澤隆昭¹

所属機関： ¹東京慈恵会医科大学脳神経外科学講座

ページ範囲：P.183 - P.198

Ⅰ．はじめに
　小児脳腫瘍は小児がんにおいて白血病に次ぐ頻度をもつ小児期最多の固形腫瘍であり，小児がんの約20〜25%を占める．小児がん治療は，20世紀医学のsuccess storyの代表とされ，小児がんによる死亡率は，最近20年も年々減少し続けている⁵⁶⁾．このような小児がん治療の残された最大の課題として筆頭に挙げられるのが脳腫瘍である⁵⁶⁾．他の固形腫瘍と同様，外科的治療・放射線治療・化学療法を併用した集学的治療は成果を挙げてきたが，脳腫瘍は今日小児がんによる死亡の最大の要因となっている⁵⁶⁾．一方，脳腫瘍は小児がんにおける合併症・後遺症の最大の要因となっている．内分泌機能障害，認知機能障害，運動障害，言語障害など，全身性疾患というべき多様な合併症を認め，多くは生涯にわたる後遺症となる．このため小児脳腫瘍患者の生存率の向上とquality of life（QOL）の向上は世界共通の急務である．
　これらの目標達成を妨げる要因として，小児脳腫瘍が全体で乳がんの約100分の1，成人脳腫瘍の約10分の1の頻度であり，100種類の異なる腫瘍から構成され，多くの腫瘍が稀少がんであることが挙げられる．成人がんのように，臨床疫学の成果を反映した臨床試験によって新しい治療法を開発していくことが困難な腫瘍が多い．さらに，神経系の発達期にあり，手術や放射線治療などの治療による障害が重篤になりやすく，治療方法に大きな制限があることが挙げられる．同じ腫瘍でも発症部位，年齢により診断・治療の方法，予後が異なる．これらの要素を考慮し，治療の合併症の可能性も考慮しながら，個々の患者に最適な診断・治療方法を選択する必要があり，複雑で困難となる．
　このような困難に直面しながらも，小児脳腫瘍治療は大きな進化をとげてきた．その基盤として，①治療のセンター化：稀少疾患を集約して診療経験を集積，②臨床試験：診療センターを連結した多施設共同臨床試験から近年の大規模国際共同試験までの新しい治療の開発，③長期フォローアップ知見の集積：重篤な後遺症，例外的な生存例の知見の臨床への還元，が挙げられる．さらに近年小児脳腫瘍において次世代シークエンスを用いた大規模なゲノム解析が急速に展開し，from bench to bedすなわち分子生物学的研究による病態解明から新しい診断・治療方法が開発される可能性が高くなっている²³⁾．これらの歴史をみれば，わが国の小児脳腫瘍の治療の進歩のため，われわれがとるべき道は明らかである．本稿では，代表的な小児脳腫瘍をとりあげ，集学的治療の中で化学療法の導入により治療がどのように変化し，さらに今後どのように変わろうとしているのか，治療の進化を概観する．

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