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

Abstract

Purpose: Treatment decisions for leptomeningeal disease (LMD) rely on patient risk strati cation, since clinicians lack objective prognostic tools. The introduction of rare cell capture technology for identi cation of cerebrospinal uid tumor cells (CSF-TCs) 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 signi cantly associated with survival. An optimal cutpoint for dichotomizing survival by CSF-TC density was 19.34 TCs/mL. The time-dependent sensitivity and speci city for survival using this strati cation 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-strati cation may help guide treatment decisions.