Carcinomatous meningitis: Leptomeningeal metastases in solid tumors.
Carcinomatous meningitis: Leptomeningeal metastases in solid tumors.
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DOI：
10.4103/2152-7806.111304
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发表时间：
2013
影响因子：
--
通讯作者：
Chamberlain MC
中科院分区：
文献类型：
--
作者：
Le Rhun E;Taillibert S;Chamberlain MC
软脑膜转移（LM）是癌症转移扩散至软脑膜的结果，导致中枢神经系统功能障碍。乳腺癌、肺癌和黑色素瘤是成人实体瘤中最常见的 LM 病因。在固定的神经功能缺损出现之前早期诊断 LM，可以更早、可能更有效地进行治疗，从而提高受影响患者的生活质量。除了临床怀疑 LM 之外，诊断还取决于脑脊液 (CSF) 中是否存在癌症或神经轴成像显示的放射学表现。目前，脑脊液中生物标志物和蛋白质分析的使用虽然不常用，但具有潜在用途。对症治疗针对疼痛，包括头痛、恶心和呕吐，而更具体的 LM 治疗包括脑脊液内化疗、全身化疗和特定部位放疗。这篇综述特别强调讨论了包括靶向治疗在内的新型药物，这些药物在未来的 LM 治疗中可能有希望。这些新疗法包括治疗非小细胞肺癌的抗表皮生长因子受体（EGFR）酪氨酸激酶抑制剂厄洛替尼和吉非替尼、治疗乳腺癌的抗HER2单克隆抗体曲妥珠单抗、抗CTLA4易普利姆玛和抗BRAF酪氨酸激酶抑制剂（例如治疗黑色素瘤的vermurafenib）以及抗血管治疗药物。 内皮生长因子单克隆抗体贝伐珠单抗目前正在 LM 患者中进行研究。管理 LM 患者面临的挑战是多方面的，包括确定适合治疗的患者以及脑脊液内药物治疗的最佳给药途径。
Leptomeningeal metastasis (LM) results from metastatic spread of cancer to the leptomeninges, giving rise to central nervous system dysfunction. Breast cancer, lung cancer, and melanoma are the most frequent causes of LM among solid tumors in adults. An early diagnosis of LM, before fixed neurologic deficits are manifest, permits earlier and potentially more effective treatment, thus leading to a better quality of life in patients so affected. Apart from a clinical suspicion of LM, diagnosis is dependent upon demonstration of cancer in cerebrospinal fluid (CSF) or radiographic manifestations as revealed by neuraxis imaging. Potentially of use, though not commonly employed, today are use of biomarkers and protein profiling in the CSF. Symptomatic treatment is directed at pain including headache, nausea, and vomiting, whereas more specific LM-directed therapies include intra-CSF chemotherapy, systemic chemotherapy, and site-specific radiotherapy. A special emphasis in the review discusses novel agents including targeted therapies, that may be promising in the future management of LM. These new therapies include anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib in nonsmall cell lung cancer, anti-HER2 monoclonal antibody trastuzumab in breast cancer, anti-CTLA4 ipilimumab and anti-BRAF tyrosine kinase inhibitors such as vermurafenib in melanoma, and the antivascular endothelial growth factor monoclonal antibody bevacizumab are currently under investigation in patients with LM. Challenges of managing patients with LM are manifold and include determining the appropriate patients for treatment as well as the optimal route of administration of intra-CSF drug therapy.