Managing leptomeningeal melanoma metastases in the era of immune and targeted therapy.
Managing leptomeningeal melanoma metastases in the era of immune and targeted therapy.
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DOI：
10.1002/ijc.30147
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发表时间：
2016-09-15
影响因子：
6.4
通讯作者：
Forsyth PA
中科院分区：
文献类型：
--
作者：
Smalley KS;Fedorenko IV;Kenchappa RS;Sahebjam S;Forsyth PA
黑色素瘤经常转移到脑部，临床上约30%的患者明显累及中枢神经系统（尸检时高达75%）。在约5%的病例中，黑色素瘤细胞也转移到脑膜、蛛网膜下腔和脑脊液。轻脑膜黑色素瘤转移（LMM）患者预后最差，其特点是疾病进展迅速（平均生存时间为8-10周），并可因神经系统原因死亡。近年来，针对黑色素瘤的靶向和免疫疗法的发展取得了巨大进展，这已经转化为增加的生存效益。尽管取得了这些进展，但大多数患者治疗失败，人们怀疑大脑和脑轻脑膜是黑色素瘤细胞的“避难所”，它们逃避了靶向治疗和免疫治疗。新出现的证据表明：1)迁移到中枢神经系统的癌细胞可能具有独特的分子特性；2)中枢神经系统/脑轻脑膜微环境是影响治疗反应的促生存生态位。在这篇小综述中，我们将概述LMM发展的临床过程，并将描述颅内免疫和细胞微环境如何为这种疾病的成功治疗提供机遇和挑战。我们将进一步讨论证明BRAF抑制剂和免疫治疗在LMM治疗中的潜在应用的最新数据，并将回顾未来治疗这一晚期黑色素瘤最具破坏性并发症的潜在治疗策略。
Melanoma frequently metastasizes to the brain, with CNS involvement being clinically evident in ~30% of patients (as high as 75% at autopsy). In ~5% cases melanoma cells also metastasize to the leptomeninges, the sub-arachnoid space and cerebrospinal fluid (CSF). Patients with leptomeningeal melanoma metastases (LMM) have the worst prognosis and are characterized by rapid disease progression (mean survival 8-10 weeks) and a death from neurological causes. The recent years have seen tremendous progress in the development of targeted and immune therapies for melanoma that has translated into an increased survival benefit. Despite these gains, the majority of patients fail therapy and there is a suspicion that the brain and the leptomeninges are a “sanctuary” sites for melanoma cells that escape both targeted therapy and immunologic therapies. Emerging evidence suggests that 1) Cancer cells migrating to the CNS may have unique molecular properties and 2) the CNS/leptomeningeal microenvironment represents a pro-survival niche that influences therapeutic response. In this Mini-Review we will outline the clinical course of LMM development and will describe how the intracranial immune and cellular microenvironments offer both opportunities and challenges for the successful management of this disease. We will further discuss the latest data demonstrating the potential use of BRAF inhibitors and immune therapy in the management of LMM, and will review future potential therapeutic strategies for the management of this most devastating complication of advanced melanoma.