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Ⅰ.はじめに
髄膜癌腫症(leptomeningeal metastasis:LM)は著しいQOLの低下を生じ,予後不良の病態である.特に肺腺癌のLMに対しては,乳癌の場合と比較し,髄腔内化学療法の効果が十分とはいえず,過去の報告でも緩和ケアで生存期間中央値が4~6週,放射線治療例で2~3カ月,メトトレキサート(MTX)髄注と放射線治療例で5カ月である1,8).
近年EGFR-tyrosine kinase inhibitor(EGFR-TKI)が,肺腺癌の他臓器転移に有効であるだけでなく,脳転移や髄膜癌腫症にも効果を認めた報告が散見される20).しかし,EGFR-TKIの血液脳関門の通過性・髄液移行性が,他の臓器への移行性よりも劣る点から,全身の癌のコントロールがよいにもかかわらず,中枢神経系のみに再発を来すことも指摘されており12),化学療法のみでは治療効果に限界がある.
このような状況のなか,当院では,LMに対して,他臓器転移がコントロールされている症例には積極的に集学的治療を行ってきた.LMでは,高率に水頭症を合併するため,脳室腹腔シャント術(VPシャント)を施行し,著明な症状改善を得ることができた.さらに,他臓器転移が制御され,状態のよい症例には,全脳全脊髄照射も選択肢の1つとした.
今回,肺腺癌からのLMに対し,EGFR-TKIとVPシャントと放射線治療を組み合わせた集学的治療が奏功した4例を報告する.
Background: Leptomeningeal metastasis (LM) is a devastating complication of systemic cancers. New therapies that have beneficial effects on primary cancers outside the central nervous system (CNS) have underscored the significance of LM. Intrathecal chemotherapy plus radiation therapy are less effective for LM from lung adenocarcinoma. We retrospectively studied outcomes of patients with LM from lung adenocarcinoma who underwent multidisciplinary treatments in our institute.
Methods: Four patients with LM from lung adenocarcinoma treated with EGFR-TKI, VP shunt and irradiation. Of those four, two presented with increased intracranial pressure, one with epilepsy, and the other with truncal ataxia. Treatment was indicated when LM was confirmed by MR images or cytology, and Karnofsky Performance Status scale was more than 40%, and life expectancy was more than three months if LM was controlled. EGFR mutation was not examined, because of the unsettled approval of Japanese public health insurance at the time of this study. The patients selected for treatment by EGFR-TKI were all Asian women who had never smoked. Treatment sequence was based on clinical symptoms depending on the individual situation.
Result: The mean time from diagnosis of lung adenocarcinoma to LM onset was 28 (24 to 36) months. Mean survival time from LM diagnosis was 9 months. All patients died of LM. No patients suffered from peritoneal carcinomatosis or infection after VP shunt.
Conclusion: The triple modality combination of EGFR-TKI,VP shunt and radiation therapy may improve outcomes and symptoms of patients with LM from lung adenocarcinoma.
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