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Review
. 2025 Mar;172(1):31-40.
doi: 10.1007/s11060-024-04902-0. Epub 2024 Dec 20.

Cerebral spinal fluid analyses and therapeutic implications for leptomeningeal metastatic disease

Jie Wei Zhu #  1 , Megan Shum #  1 , Maleeha A Qazi  2 , Arjun Sahgal  2   3 , Sunit Das  4 , Matthew Dankner  5 , Ines Menjak  1   6 , Mary Jane Lim-Fat  7 , Katarzyna J Jerzak  8   9   10
Affiliations
Review

Cerebral spinal fluid analyses and therapeutic implications for leptomeningeal metastatic disease

Jie Wei Zhu et al. J Neurooncol. 2025 Mar.

Abstract

Purpose: To review applications of cerebral spinal fluid (CSF) biomarkers for the diagnosis, monitoring and treatment of leptomeningeal metastatic disease (LMD) among patients with metastatic solid tumors.

Methods: A narrative review identified original research related to CSF biomarkers among patients with metastatic solid tumors and LMD. Pre-clinical research (e.g. studies conducted in animal models) was not included. A descriptive analysis of literature was undertaken, with a focus on clinical applications related to the diagnosis, monitoring and treatment of LMD.

Results: The low cellularity of CSF in comparison to plasma is an advantage for liquid biopsy, given that circulating tumor DNA (ctDNA) is not significantly diluted by genomic DNA from non-cancer cells. This results in higher variant allelic frequencies and increased sensitivity in detecting ctDNA compared to plasma. However, the clinical significance of positive ctDNA and/or circulating tumor cells (CTCs) in the CSF, particularly in the absence of other signs of LMD (either clinical and/or radiological), remains unclear. While the use of CSF liquid biopsy to monitor treatment response is promising, this approach requires prospective validation using larger sample sizes prior to adoption in routine clinical care. Discovery efforts involving proteomics and metabolomics have potential to identify proteins involved in the regulation of energy metabolism, vasculature, and inflammation in LMD, which in turn, may offer insights into novel treatment approaches.

Conclusion: CSF liquid biopsy should be incorporated in prospective studies for patients with LMD to validate promising diagnostic and/or predictive biomarkers of treatment response, as well as new therapeutic targets.

Keywords: Biomarkers; Cerebral spinal fluid; Circulating tumor cells; Circulating tumor DNA; Leptomeningeal metastatic disease; Liquid biopsy.

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Conflict of interest statement

Declarations. Competing interests: A.S. reports: grants from Elekta, Varian, Seagen Inc., BrainLAB, consulting fees from Varian, Elekta, BrainLAB, Merck, Abbvie, Roche, honoraria from AstraZeneca, Elekta, Varian, BrainLAB, Accuray, Seagen Inc., travel expenses from Elekta, Varian, BrainLAB, roles on leadership board as Vice President of International Stereotactic Radiosurgery Society and other interests as member of Elekta MR-Linac Research Consortium, member of Elekta Clinical Steering Committee, chair of Elekta Oligometastases Group and Elekta Gamma Knife Icon Group. S.D. reports grant funding from the Canadian Institutes of Health Research, Gratitude 10, the Canadian Cancer Society, the Calum Macbeth fund, Synaptive, VPIX, and the Keenan Chair in Surgery, royalties from Oxford University Press, travel and accommodation from the Congress of Neurological Surgeons and the American Association of Neurological Surgeons, data safety monitoring board or advisory board for the Subcortical Surgery Group, and is the Provincial Lead for CNS Cancers at Ontario Health, Cancer Care Ontario. I.M. reports: honoraria from AstraZeneca and Merck, education funding from AstraZeneca. M.L. reports: Advisory Board for Servier, Novocure. K.J.J has been a consultant, speaker, or advisory board member for Amgen, AstraZeneca, Apo Biologix, Daiichi Sankyo, Eli Lilly, Esai, Genomic Health, Gilead Sciences, Knight Therapeutics, Merck, Myriad Genetics, Novartis, Organon, Pfizer, Roche, and Viatris; has received research funding from AstraZeneca, Eli Lilly, and Pfizer; has received support for attending meetings or travel from AstraZeneca and Daiichi Sankyo; has a patent regarding compounds for treating cancer and methods of use thereof (US patent 10 576 056; Europe patent 3 393 466); and has received drug supply from Pfizer and Viatris for an investigator initiated clinical trial.

References

    1. Remsik J, Boire A (2024) The path to leptomeningeal metastasis. Nat Rev Cancer 24(7):448–460. https://doi.org/10.1038/s41568-024-00700-y - DOI - PubMed - PMC
    1. Le Rhun E, Weller M, Brandsma D et al (2017) EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours. Ann Oncol 28:iv84–iv99 - DOI - PubMed
    1. Nayar G, Ejikeme T, Chongsathidkiet P, Elsamadicy AA, Blackwell KL, Clarke JM, Lad SP, Fecci PE (2017) Leptomeningeal disease: current diagnostic and therapeutic strategies. Oncotarget 8(42):73312 - DOI - PubMed - PMC
    1. Tewarie IA, Jessurun CAC, Hulsbergen AFC et al (2021) Leptomeningeal disease in neurosurgical brain metastases patients: a systematic review and meta-analysis. Neurooncol Adv. 3(1):vdab162. https://doi.org/10.1093/noajnl/vdab162 - DOI - PubMed - PMC
    1. Lowe SR, Wang CP, Brisco A et al (2022) Surgical and anatomic factors predict development of leptomeningeal disease in patients with melanoma brain metastases. Neuro Oncol 24(8):1307–1317. https://doi.org/10.1093/neuonc/noac023 - DOI - PubMed - PMC

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