Sorbonne Université, INSERM, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) S 1127, Institut du Cerveau et de la Moelle épinière (ICM), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix Service de Neurologie 2-Mazarin, Paris, France.
Sorbonne Université, INSERM, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) S 1127, Institut du Cerveau et de la Moelle épinière (ICM), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix Service de Neuropathologie-Escourolle, Paris, France.
Oncologist. 2020 Nov;25(11):e1763-e1776. doi: 10.1634/theoncologist.2020-0258. Epub 2020 Aug 31.
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. Leptomeningeal spread (LMS) is a severe complication of GBM, raising diagnostic and therapeutic challenges in clinical routine.
We performed a review of the literature focused on LMS in GBM. MEDLINE and EMBASE databases were queried from 1989 to 2019 for articles describing diagnosis and therapeutic options in GBM LMS, as well as risk factors and pathogenic mechanisms.
We retrieved 155 articles, including retrospective series, case reports, and early phase clinical trials, as well as preclinical studies. These articles confirmed that LMS in GBM remains (a) a diagnostic challenge with cytological proof of LMS obtained in only 35% of cases and (b) a therapeutic challenge with a median overall survival below 2 months with best supportive care alone. For patients faced with suggestive clinical symptoms, whole neuroaxis magnetic resonance imaging and cerebrospinal fluid analysis are both recommended. Liquid biopsies are under investigation and may help prompt a reliable diagnosis. Based on the literature, a multimodal and personalized therapeutic approach of LMS, including surgery, radiotherapy, systemic cytotoxic chemotherapy, and intrathecal chemotherapies, may provide benefits to selected patients. Interestingly, molecular targeted therapies appear promising in case of actionable molecular target and should be considered.
As the prognosis of glioblastoma is improving over time, LMS becomes a more common complication. Our review highlights the need for translational studies and clinical trials dedicated to this challenging condition in order to improve diagnostic and therapeutic strategies.
This review summarizes the diagnostic tools and applied treatments for leptomeningeal spread, a complication of glioblastoma, as well as their outcomes. The importance of exhaustive molecular testing for molecular targeted therapies is discussed. New diagnostic and therapeutic strategies are outlined, and the need for translational studies and clinical trials dedicated to this challenging condition is highlighted.
胶质母细胞瘤（GBM）是最常见且侵袭性最强的原发性恶性脑肿瘤。软脑膜播散（LMS）是 GBM 的一种严重并发症，在临床常规中带来了诊断和治疗方面的挑战。
我们对专注于 GBM 中 LMS 的文献进行了综述。从 1989 年到 2019 年，我们在 MEDLINE 和 EMBASE 数据库中查询了描述 GBM LMS 诊断和治疗选择以及风险因素和发病机制的文章。
我们检索到 155 篇文章，包括回顾性系列、病例报告和早期临床研究，以及临床前研究。这些文章证实，GBM 中的 LMS 仍然存在：（a）诊断挑战，仅在 35%的病例中获得 LMS 的细胞学证据；（b）治疗挑战，单独采用最佳支持治疗，中位总生存期低于 2 个月。对于出现提示性临床症状的患者，建议同时进行全脑磁共振成像和脑脊液分析。液体活检正在研究中，可能有助于做出可靠的诊断。基于文献，LMS 的多模式和个体化治疗方法，包括手术、放疗、全身细胞毒性化疗和鞘内化疗，可能为选定的患者带来益处。有趣的是，在存在可操作的分子靶点的情况下，分子靶向治疗似乎很有前景，应予以考虑。
随着胶质母细胞瘤的预后随着时间的推移而改善，LMS 成为更常见的并发症。我们的综述强调了开展转化研究和临床试验的必要性，以改善针对这种具有挑战性的疾病的诊断和治疗策略。
本综述总结了胶质母细胞瘤并发症软脑膜播散的诊断工具和应用治疗方法及其结果。讨论了进行全面分子检测以进行分子靶向治疗的重要性。概述了新的诊断和治疗策略，并强调了开展针对这种具有挑战性疾病的转化研究和临床试验的必要性。
