Utility of cerebrospinal fluid circulating tumor cell quantification and next-generation sequencing in patients with suspicion for leptomeningeal disease

Abstract Background Leptomeningeal disease (LMD) is characterized by the spread of cancer to the leptomeninges and cerebrospinal fluid (CSF) and is associated with poor survival. Diagnosing LMD is challenging, as traditional methods such as MRI and CSF cell cytology demonstrate variable sensitivity. This study aims to explore the diagnostic potential of CSF circulating tumor cell (CTC) quantification for LMD in conjunction with current standards. Methods This retrospective case series includes 12 patients with suspected LMD who underwent CSF analysis with the CNSide™ assay for CTC quantification and next-generation sequencing (NGS), alongside MRI and CSF cytology. Relying on a composite definition of LMD-positive, the diagnostic performance of CTC quantification was assessed. Results Of 12 patients evaluated for LMD with CNSide™, 11 were found to have brain metastases (BM). Lung carcinoma was the most common primary cancer (4/12). Nine patients were deemed LMD-positive based on clinical criteria: 7/9 had a preceding brain metastasis diagnosis, while 2/9 co-presented with LMD and BM. CNSide™ detected CTCs in 7/12 patients (7/9 of those with LMD) and influenced clinical decision-making by guiding chemotherapy selection and prompting proton craniospinal irradiation. Of the three patients deemed LMD-negative with clinical criteria, all three had negative results on the CNSide™ assay. The CNSide™ assay demonstrated a sensitivity of 77.8%, specificity of 100%, and overall accuracy of 83.3%. Conclusion The integration of CTC quantification with next-generation sequencing (NGS) can be a valuable adjunct to cell cytology in diagnosing leptomeningeal disease. CSF liquid biopsy may provide earlier detection and inform treatment decisions, ultimately improving patient outcomes.