Diagnostic Utility and Prognostic Significance of Circulating Tumor Cell Assay CNSide in Patients With Suspicion for Leptomeningeal Metastases
Shreya Louis1, George Nageeb3, Seema Nagpal2, David Rogawski4
1Neurology, 2Neuro-Oncology, Stanford Health Care, 3Stanford School of Medicine, 4Stanford University
Objective:

To evaluate diagnostic utility and prognostic significance of CNSide circulating tumor cell (CTC) assay in cerebrospinal fluid (CSF) of patients with suspicion for leptomeningeal metastases (LM).

Background:

The CNSide assay uses an antibody cocktail to capture and detect CSF CTCs, resulting in increased sensitivity for LM over cytology. It remains unclear whether survival of CNSide-positive cytology-negative patients differs from that of cytology-positive patients or whether CNSide testing is useful in cancer patients who have alternative diagnosis presenting with LM signs or symptoms.

Design/Methods:

Ninety-nine patients treated at Stanford between 2020 and 2023 underwent cytology and CNSide testing from the same lumbar puncture (LP). Patients were classified as having Type 1 (cytology positive), Type 2 Probable (both radiographic and clinical features), or Type 2 Possible LM (either radiographic or clinical features) at the time of LP. Patients were followed over time and given a retrospective diagnosis (confirmed LM vs. alternative diagnosis). Survival curves, sensitivity, and specificity were calculated using R v4.4.

Results:

Of 99 patients, 43 had Type 1 LM, 23 had Type 2 Probable LM, 13 had Type 2 Possible LM, and 20 were determined retrospectively to have an alternative diagnosis. CNSide had superior sensitivity over cytology (75.3% vs 51.9%). CNSide specificity was 89.5%, with two false positives likely resulting from peripheral blood contamination of CSF. Median survival in CNSide-positive cytology-negative patients was not significantly different compared to cytology-positive patients (5.81 vs 6.29 months, p=0.879. CNSide-negative LM patients had a longer median survival compared to CNSide-positive patients (40.8 vs 5.8 months, p=0.017).

Conclusions:

In this retrospective cohort, LM patients with positive CNSide but negative/inconclusive cytology have similar overall survival as patients with positive CSF cytology. Given its improved sensitivity compared to cytology and high specificity, CNSide is a useful test for clinicians evaluating cancer patients with signs and symptoms of LM.

10.1212/WNL.0000000000216414
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