Abstract
Circulating tumor cells in cerebrospinal fluid are a quantitative diagnostic tool for leptomeningeal metastases from solid tumors, but their prognostic significance is unclear. Our objective was to evaluate CSF-CTC quantification in predicting outcomes in LM. This is a single institution retrospective study of patients with solid tumors who underwent CSF-CTC quantification using the CellSearch® platform between 04/2016 and 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 identified through recursive partitioning analysis. Out of 290 patients with CNS metastases, we identified 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 findings 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. Our data shows that CSF-CTCs quantification 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.
Highlights
Leptomeningeal metastases (LM) are a devastating complication of solid tumors, with breast and lung cancers having the highest incidence among all malignancies
Out of 290 patients with CNS metastases, we identified a cohort of 101 patients with newly diagnosed leptomeningeal metastases (LM)
Our data shows that cerebrospinal fluid (CSF)-Circulating tumor cells (CTC) quantification predicts survival in newly diagnosed LM, and outperforms neuroimaging
Summary
Leptomeningeal metastases (LM) are a devastating complication of solid tumors, with breast and lung cancers having the highest incidence among all malignancies. The CellSearch® Circulating Tumor Cell test, which utilizes epithelial cell adhesion molecule (EpCAM)-based rare cell capture technology to immunomagnetically isolate and enumerate CTCs and detect metastatic cancer from epithelial tumors, has been validated in CSF on the CellTracks Analyzer II® as a highly sensitive and specific platform for LM diagnosis[14]. This test is FDA approved in blood for patients with several types of metastatic carcinoma, where a correlation between CTC count and prognosis, response to treatment, and tumor burden has been shown[15,16,17,18]
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