Leptomeningeal disease: Current approaches and future directions Review


Authors: Sener, U.; Wilcox, J. A.; Boire, A. A.
Review Title: Leptomeningeal disease: Current approaches and future directions
Abstract: Purpose of Review: Leptomeningeal disease (LMD), or spread of cancer cells into the pia and arachnoid membranes encasing the brain and spinal cord, is associated with high symptom burden and poor survival at 2 to 5 months. Conventional treatments including photon-based radiation therapy, systemic chemotherapy, and intrathecal chemotherapy demonstrate limited efficacy. Despite significant successes for a range of solid tumors, immunotherapy has not yet demonstrated significant efficacy in management of LMD. Advances in understanding of LMD pathophysiology, improved diagnostics, and novel therapeutics are shifting this paradigm. In this article, we review diagnostic and treatment challenges associated with LMD. Recent Findings: We discuss the use of novel cerebrospinal fluid (CSF) analysis techniques such as circulating tumor cell and CSF cell-free DNA assessment to overcome limitations of conventional diagnostic modalities. We then review advances in treatment including clinical trial data demonstrating efficacy of proton craniospinal radiation to treat the entire neuroaxis. We discuss emerging data regarding targeted therapeutics conferring durable survival benefit. Summary: Novel therapeutics and combinatorial treatment approaches will likely further improve outcomes for patients with LMD. © The Author(s) 2025.
Keywords: clinical trial; review; solid tumor; pathophysiology; metastasis; radiotherapy; immunotherapy; drug combination; cerebrospinal fluid; spinal cord; diagnosis; drug administration; drug therapy; therapy; circulating tumor cell; cerebrospinal fluid cytology; arachnoid; central nervous system metastasis; leptomeningeal metastases; leptomeningeal disease; central nervous system metastases; symptom burden; human; craniospinal radiation; intrathecal therapy; intrathecal drug administration; circulating free dna
Journal Title: Current Neurology and Neuroscience Reports
Volume: 25
ISSN: 1528-4042
Publisher: Springer  
Date Published: 2025-03-18
Start Page: 25
Language: English
DOI: 10.1007/s11910-025-01412-y
PROVIDER: scopus
PMCID: PMC11920312
PUBMED: 40100294
DOI/URL:
Notes: Review -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Adrienne Boire -- Source: Scopus
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MSK Authors
  1. Adrienne Boire
    106 Boire
  2. Jessica Alice Wilcox
    34 Wilcox