Prognostic value of cerebrospinal fluid tumor cell count in leptomeningeal disease from solid tumors

J Neurooncol. 2024 May;167(3):509-514. doi: 10.1007/s11060-024-04615-4. Epub 2024 Mar 5.

Abstract

Purpose: Treatment decisions for leptomeningeal disease (LMD) rely on patient risk stratification, since clinicians lack objective prognostic tools. The introduction of rare cell capture technology for identification of cerebrospinal fluid tumor cells (CSF-TCs), such as CNSide assay, improved the sensitivity of LMD diagnosis, but prognostic value is unknown. This study assesses the prognostic value of CSF-TC density in patients with LMD from solid tumors.

Methods: We conducted a retrospective cohort study of patients with newly diagnosed or previously treated LMD from a single institution who had CNSide assay testing for CSF-TCs from 2020 to 2023. Univariable and multivariable survival analyses were conducted with Cox proportional-hazards modeling. Maximally-selected rank statistics were used to determine an optimal cutpoint for CSF-TC density and survival.

Results: Of 31 patients, 29 had CSF-TCs detected on CNSide. Median (interquartile range [IQR]) CSF-TC density was 67.8 (4.7-639) TCs/mL. CSF cytology was positive in 16 of 29 patients with positive CNSide (CNSide diagnostic sensitivity = 93.5%, negative predictive value = 85.7%). Median (IQR) survival from time of CSF-TC detection was 176 (89-481) days. On univariable and multivariable analysis, CSF-TC density was significantly associated with survival. An optimal cutpoint for dichotomizing survival by CSF-TC density was 19.34 TCs/mL. The time-dependent sensitivity and specificity for survival using this stratification were 76% and 67% at 6 months and 65% and 67% at 1 year, respectively.

Conclusions: CSF-TC density may carry prognostic value in patients with LMD from solid tumors. Integrating CSF-TC density into LMD patient risk-stratification may help guide treatment decisions.

Keywords: Biocept; CNSide; CTC; Circulating tumor cells; LMD; Rare cell capture.

MeSH terms

  • Adult
  • Aged
  • Cell Count
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Meningeal Carcinomatosis / cerebrospinal fluid
  • Meningeal Carcinomatosis / diagnosis
  • Meningeal Carcinomatosis / mortality
  • Meningeal Neoplasms* / cerebrospinal fluid
  • Meningeal Neoplasms* / diagnosis
  • Meningeal Neoplasms* / mortality
  • Meningeal Neoplasms* / pathology
  • Middle Aged
  • Neoplasms / cerebrospinal fluid
  • Neoplasms / diagnosis
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Prognosis
  • Retrospective Studies
  • Survival Rate