Identifying leptomeningeal metastasis from breast cancer utilizing a novel immunocytochemical microfluidic device

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Abstract: The goal is to determine whether testing with a microfluidic device, known as OncoCEE, will improve the sensitivity in the diagnosis of leptomeningeal (LM) disease in patients with metastatic breast cancer (MBC) compared to standard cytopathologic analysis. Diagnosing LM can be clinically challenging. Repeat multi-site and high volume lumbar punctures are often required, leading to patient complications, treatment delays, and patient discomfort. There is an unmeet need to improve the ability to identify LM, With an improved diagnostic test, providers could intervene earlier with agents that are known to cross the blood brain barrier, including systemic chemotherapy and/or intrathecal therapy. In this study, we will prospectively enroll 36 patients with MBC who are undergoing workup for clinical suspicion of LM. Specific Aim #1 is to assess whether OncoCEE Cell Enrichment and Extraction improves the sensitivity in the diagnosis of LM in patients with unequivocal or suspicious findings for LM on magnetic resonance imaging compared to standard cerebrospinal fluid analysis (n=36 patients). Specific Aim #2 is to evaluate the concordance of hormone receptor and HER2 status between the spinal fluidic cells identified by OncoCEE Cell Enrichment and Extraction and metastatic tissue, in those with LM disease by OncoCEE (n=32 patients, anticipated in 90% of the 36 total participants). We hypothesize that OncoCEE Cell Enrichment and Extraction will have an improved sensitivity in LM diagnosis compared to standard cytology. In addition, we anticipate that OncoCEE Cell Enrichment and Extraction will have substantial concordance of the hormone receptor and HER2 status in cells identified in the spinal fluid and metastatic tissue, or primary tissue if metastatic biopsy not available. This aim is clinically relevant, as Estrogen Receptor/Progesterone Receptor/HER2 are important factors for prediction of treatment response and ultimate selection of therapeutic agents. Cytologic determination of LM remains the gold standard. Improving on this with a more reliable system would decrease the burden of multiple lumbar punctures, including the risks of repeated attempts, and potentially cost, as current clinical practice requires magnetic resonance imaging. If this system were found to be better than standard cytology, with substantial concordance in immunophenotype with metastatic tissue, the next step would be a larger, multi-center trial with this device, incorporating next generation sequencing of spinal fluid. This would be in line with the goal of focusing on precision medicine in cancer treatment.