Added prognostic value of circulating tumor cell numbers in CSF of patients with leptomeningeal metastasis from epithelial tumors

Abstract

BACKGROUND: Leptomeningeal metastases (LM) from solid tumors are described in up to 10 % of patients, and median survival rates are low. Advanced techniques for circulating tumor cell enumeration in cerebrospinal fluid (CSF) can help in diagnosing patients with LM but also could have value in prognostication. Our aim was to investigate whether the number of circulating tumor cells (CTCs) in CSF are of added value in survival prediction in LM patients. METHODS: We performed a single-center retrospective study in a cohort of consecutive patients with LM from epithelial tumors. Circulating tumor cells in CSF were measured by an Epithelial Cell Adhesion Molecule (EpCAM)-based immunoflow cytometry method at LM diagnosing. The added prognostic value of the number of CTCs in CSF on top of known clinical prognostic factors for LM was assessed. We compared Cox proportional hazards regression models with and without CTCs by discriminative performance measures. RESULTS: We included 103 eligible patients with epithelial tumors (60 % NSCLC, 29 % breast cancer), who were diagnosed with either possible, probable, or confirmed LM according to EANO-ESMO criteria. Median survival was 129 days. CTC numbers in CSF were of significant added prognostic value in a multivariable prognostic model (HR = 1.86, 95 % CI = 1.26-2.76, likelihood ratio test p-value=0.003 for models with CTCs versus without CTCs). CONCLUSION: Our findings indicate that the number of CTCs in CSF, as measured by EpCAM immunoflow cytometry, are of additional prognostic value to other well-known clinical predictors of survival in LM. The number of CTCs in CSF should be taken in account when assessing the prognosis of patients with LM.