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Review

The early recognition and diagnosis of neoplastic meningitis

ORCID Icon, ORCID Icon, , & ORCID Icon
Pages 105-116 | Received 18 Jul 2023, Accepted 06 Dec 2023, Published online: 25 Dec 2023
 

ABSTRACT

Introduction

The diagnosis and monitoring of leptomeningeal metastases (LM) from solid tumors are challenging, and the combination of neurological symptoms, MRI findings, and cerebrospinal fluid (CSF) cytology does not always allow to achieve a definitive diagnosis.

Areas covered

This review summarizes the studies that have investigated CSF liquid biopsy to improve the initial diagnosis of LM in case the CSF cytology is negative or only suspicious for tumor cells, and monitoring of tumor response following targeted therapies or immunotherapy. In this regard, the early detection of LM recurrence and the development of resistant mutations are critical issues. Moreover, the early identification of subgroups of patients with a higher risk of LM progression, as well as the correlation of LM burden with survival, are discussed.

Expert opinion

There is an urgent need of prospective studies to monitor longitudinally LM using CSF liquid biopsy and investigate the role of CTC, ctDNA or novel assays. The optimal setting for the longitudinal CSF and blood collection can be clinical trials focused on the molecular diagnosis of LM as well as the response and monitoring following targeted agents.

Article highlights

  • . The diagnosis and monitoring of leptomeningeal metastases (LM) from solid tumors are challenging.

  • CSF liquid biopsy can recapitulate the biology of LM and reveal molecular heterogeneity as compared with primary solid tumors.

  • Although most of studies are retrospective and comprise small, heterogeneous cohorts of patients, CSF CTCs or ctDNA could improve the accuracy of the initial diagnosis of leptomeningeal metastasis, when associated with CSF cytology.

  • The optimal use of CTCs and/or ctDNA in the setting of diagnosis (e.g. cutoff values, type of assays), monitoring, and guidance of treatment decisions has to be defined.

  • Prospective studies and clinical trials are the best setting to address these issues.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.

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