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).

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.

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.

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).

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.