Diagnosing LM is challenging due to variability in clinical symptoms, radiographic findings, and CSF results. The National Comprehensive Cancer Network (NCCN) guidelines recommend using circulating tumor DNA (ctDNA) to enhance the sensitivity of tumor cell detection and assess treatment response, when available.

We hypothesize that an assay for the direct detection and enumeration of circulating tumor cells (CTCs) in the cerebrospinal fluid (CSF) improves the accuracy of diagnosing leptomeningeal metastasis (LM), particularly at an early disease stage.

We report a series of 55 patients with a cancer diagnosis and either neurological symptoms or radiographic findings suggestive of LM. All patients underwent lumbar puncture, assessment for CTCs, and conventional hospital-based cytology between 6/1/2020 and 8/1/2023.

Of the 55 patients tested, 30 were positive for CTCs. Only 10 patients were positive by both CTC and conventional cytology, while 20 CTC-positive patients had negative cytology. No patients with a negative CTC result were later diagnosed with LM, while 4 patients with a positive CTC result did not develop progressive neurological symptoms.

The histologic breakdown of LM cases was: breast (11), non-small cell lung cancer (NSCLC) (16), gastrointestinal (GI) (3). Median overall survival was significantly longer in breast cancer LM compared to NSCLC LM (235 vs. 63 days, p = 0.008). Most patients diagnosed with LM received therapies including Ommaya reservoir placement, intrathecal chemotherapy, and radiation.

The CSF CTC assay improved the diagnosis of LM and facilitated timely treatment. A negative CTC assay was associated with ruling out LM, while a negative cytology result would have misdiagnosed 66% of patients at the time of lumbar puncture. Breast cancer LM showed improved survival compared to NSCLC and GI cancers.