Section of Virology and Immunotherapy, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
Department of Neurosurgery, Miller School of Medicine, University of Miami, 1475 NW 12th Ave, Miami, FL, 33136, USA.
J Neurooncol. 2024 Mar;167(1):39-47. doi: 10.1007/s11060-024-04582-w. Epub 2024 Jan 31.
Leptomeningeal disease (LMD) secondary to high grade glioma (HGG), such as glioblastoma (GBM), are characterized by the spread of tumor cells to the leptomeninges which further complicates treatment approaches. Intrathecal (IT) chemotherapy has surfaced as a potential strategy to bypass the blood-brain barrier and address the challenges posed by disseminated disease. Here, we present a review of the safety and efficacy of IT chemotherapy in the treatment of LMD secondary to HGG.
A systematic review following PRISMA guidelines was conducted searching PubMed and Embase from January 1995 to September 2022 using specified terms related to IT chemotherapy for LMD. Included articles involved patients diagnosed with LMD from HGG, treated with intrathecal chemotherapy, and provided survival data. Data, including demographics, tumor characteristics, treatment, and survival information, were collected and independently extracted.
A total of 68 patients across 10 clinical studies were diagnosed with LMD from HGG and included in the review. Among these patients, the average age at diagnosis was 44.2 years. GBM was the most common tumor type (n = 58, 85.3%). A majority of the patients presented with recurrent disease (n = 29, 60.4%). The review encompassed various IT chemotherapy regimens, including mafosfamide, thio-TEPA, 5-fluoro-2'-deoxyuridine (FdUrd), methotrexate (MTX), and cytarabine; however, dosages and frequencies were inconsistently reported. The mean progression-free survival (PFS) and overall survival (OS) for this cohort were 7.5 months and 11.7 months, respectively. Common side effects of IT chemotherapy included headaches, nausea, and vomiting, with more severe complications such as myelotoxicity, disseminated intravascular coagulopathy, meningitis, and gastrointestinal toxicity reported in some cases.
LMD continues to be an uncommon complication associated with HGG with a poor prognosis. This article provides an overview of the presently available literature on IT chemotherapy for LMD secondary to HGG, and their respective treatment protocols with overall survival attributes. Additional research is warranted to ascertain how to maximize the potential efficacy of IT chemotherapy as a treatment option.
高级别神经胶质瘤（HGG），如胶质母细胞瘤（GBM），引起的脑膜疾病（LMD）的特点是肿瘤细胞扩散到软脑膜，这进一步使治疗方法复杂化。鞘内（IT）化疗已成为一种潜在的策略，可以绕过血脑屏障并解决播散性疾病带来的挑战。在这里，我们回顾了 IT 化疗治疗 HGG 继发 LMD 的安全性和有效性。
按照 PRISMA 指南，对 1995 年 1 月至 2022 年 9 月在 PubMed 和 Embase 上使用与 IT 化疗治疗 LMD 相关的特定术语进行了系统评价。纳入的文章涉及诊断为 HGG 引起的 LMD 的患者，接受 IT 化疗治疗，并提供生存数据。收集并独立提取数据，包括人口统计学、肿瘤特征、治疗和生存信息。
共有 10 项临床研究中的 68 例患者被诊断为 HGG 继发 LMD，并纳入了本综述。在这些患者中，平均诊断年龄为 44.2 岁。GBM 是最常见的肿瘤类型（n=58，85.3%）。大多数患者表现为复发性疾病（n=29，60.4%）。该综述涵盖了各种 IT 化疗方案，包括氨磷汀、噻替派、5-氟-2'-脱氧尿苷（FdUrd）、甲氨蝶呤（MTX）和阿糖胞苷；然而，剂量和频率报告不一致。该队列的平均无进展生存期（PFS）和总生存期（OS）分别为 7.5 个月和 11.7 个月。IT 化疗的常见副作用包括头痛、恶心和呕吐，在某些情况下还报告了更严重的并发症，如骨髓毒性、弥漫性血管内凝血、脑膜炎和胃肠道毒性。
LMD 仍然是 HGG 的一种罕见并发症，预后较差。本文综述了目前关于 HGG 继发 LMD 的 IT 化疗文献，并介绍了它们各自的治疗方案和总生存情况。需要进一步的研究来确定如何最大限度地提高 IT 化疗作为治疗选择的潜在疗效。
