Site Editor
Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Monday, March 3, 2025
Cerebrospinal fluid (CSF)-derived circulating tumor cell–based assay may be more sensitive for the diagnosis of leptomeningeal disease in non–small cell lung cancer (NSCLC) than standard CSF cytology, according to a study conducted by Ravi Salgia, MD, PhD, of City of Hope, Duarte, California, and colleagues. In fact, 38% of leptomeningeal disease cases were missed by a standard CSF assay, whereas CSF cell-free DNA (cfDNA) molecular profiling was 100% concordant with tissue-based next-generation sequencing. The findings of this prospective, single-center study were published in JCO Precision Oncology.
“The diagnosis of leptomeningeal disease can be challenging because of the limited sensitivity of initial CSF cytology and magnetic resonance imaging and the high variability of presentation between patients,” stated the study investigators. “To our knowledge, this is one of the first studies reporting on the feasibility of CSF-derived circulating tumor cells and cfDNA in diagnosing leptomeningeal disease and evaluating the molecular profiles in [central nervous system] for patients with metastatic NSCLC.”
The study included 22 patients with metastatic NSCLC who underwent CSF collection for suspected leptomeningeal disease. CSF samples were analyzed for circulating tumor cells and cfDNA using the CNSide assay. Molecular profiling was performed on CSF cfDNA, and the results were compared with tumor tissue and plasma circulating tumor DNA. Expression of cMET and HER2 in CSF samples was evaluated using fluorescence in situ hybridization.
Leptomeningeal disease was diagnosed in 59% of patients using the CSF circulating tumor cell assay. Among them, 38% had negative CSF cytology, and 15% had normal MRI findings. Molecular profiling was feasible in seven patients (54%), identifying driver mutations with 100% concordance to tissue-based next-generation sequencing. Expression of cMET was detected in 50% of patients, whereas HER2 was observed in 18%. These results demonstrate the potential of CTC-based CSF analysis as a sensitive tool for diagnosing leptomeningeal disease and detecting potential therapeutic molecular targets.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
JNCCN Spotlights
