Quantitative assessment of circulating tumor cells in cerebrospinal fluid as a clinical tool to predict survival in leptomeningeal metastases

Abstract

Circulating tumor cells (CTC) in cerebrospinal uid (CSF) are a quantitative diagnostic tool for leptomeningeal metastases (LM) from solid tumors, but their prognostic signi cance is unclear. Our objective was to evaluate CSF-CTC quanti cation in predicting outcomes in LM. MethodsThis is a single institution retrospective study of patients with solid tumors who underwent CSF-CTC quanti cation using the CellSearch® platform between 04/2016-06/2019. Information on neuroaxis imaging, CSF results, and survival was collected. LM was diagnosed by MRI and/or CSF cytology. Survival analyses were performed using multivariable Cox proportional hazards modeling, and CSF-CTC splits associated with survival were identi ed through recursive partitioning analysis. ResultsOut of 290 patients with CNS metastases, we identi ed a cohort of 101 patients with newly diagnosed LM. In this group, CSF-CTC count (median 200 CTCs/3ml) predicted survival continuously (HR = 1.005, 95% CI: 1.002-1.009, p = 0.0027), and the risk of mortality doubled (HR = 2.84, 95% CI: 1.45-5.56, p = 0.0023) at the optimal cutoff of ≥ 61 CSF-CTCs/3ml. Neuroimaging ndings of LM (assessed by 3 independent neuroradiologists) were associated with a higher CSF-CTC count (median CSF-CTCs range 1.5-4 for patients without radiographic LM vs 200 for patients with radiographic LM, p<0.001), but did not predict survival. ConclusionOur data shows that CSF-CTCs quanti cation predicts survival in newly diagnosed LM, and outperforms neuroimaging. CSF-CTC analysis can be used as a prognostic tool in patients with LM and provides quantitative assessment of disease burden in the CNS compartment.

Randomized Phase II Trial of Proton Craniospinal Irradiation Versus Photon Involved-Field Radiotherapy for Patients With Solid Tumor Leptomeningeal Metastasis

“…5,33,[41][42][43][44] CSF CTC count has been shown to be a valuable tool to predict survival in patients with LM. 45 In an exploratory analysis, we determined that baseline CTC count is a predictive biomarker of CNS control and survival in patients treated with pCSI, confirming our prior results. 23 Furthermore, although pCSI is associated with overall decrease in CTC count after treatment, increase in CTC count was observed after IFRT and was associated with poorer outcomes for these patients.…”

Leptomeningeal Disease (LMD) in Patients with Melanoma Metastases

“…Thus, researchers investigated the possibility of detecting CTC in CSF to confirm LM diagnosis. In melanoma, CSF circulating melanoma cells (CSFMC) expressing CD146+, molecular weight melanoma-associated antigen (HMW-MAA) have been successfully identified using the CellSearch ® Veridex method [ 83 , 84 , 85 ].…”

Liquid biopsy for brain metastases and leptomeningeal disease in patients with breast cancer

“…In patients with LMD, the prognostic value of CSF-CTCs was recently confirmed by a large retrospective analysis. In this study, in which 35 out of 101 patients included had MBC, risk of death was more than double in patients with a CSF-CTC count at or above the optimal cutoff of 61 CSF-CTCs/3 mL (hazard ratio 2.84, p = 0.002) 39 . More prospective studies are needed to understand whether CTCs in CSF can be routinely used to assess prognosis and guide therapy.…”