Cerebrospinal fluid-derived circulating tumor DNA is more comprehensive than plasma in NSCLC patients with leptomeningeal metastases regardless of extracranial evolution.

INTRODUCTION

Metastases to the central nervous system (CNS) are devastating neurological complications. Circulating cell-free tumor DNA (ctDNA) from cerebrospinal fluid (CSF) better represents genomic alterations in CNS tumors compared to plasma (PLA). However, the clinical value of cerebrospinal fluid (CSF) as a liquid biopsy medium in non-small cell lung cancer patients with leptomeningeal metastases (NSCLC-LM), regardless of extracranial evolution, remains unclear.

PATIENTS AND METHODS

14/48 NSCLC-BM patients and 34/48 NSCLC-LM patients were enrolled in this study. The genomic mutation profiles in CSF and matched PLA for patients with single CNS progression (cohort one, N = 22) or intracranial progression with extracranial disease progression (cohort two, N = 12) were compared. ctDNA in the CSF and simultaneously collected PLA was subjected to next-generation target sequencing (NGS) of 168 cancer-relevant genes.

RESULTS

CSF is more comprehensive of driver genomic mutation profile than in matched PLA in patients with a single CNS progression. In addition, potential prognostic markers are much higher in CSF samples than related PLA. For example, the detection rate of -amp in CSF was more than twice of the rate in matched PLA. Moreover, , , and were detected uniquely in CSF samples and, all of these genetic mutations were correlated with poor outcomes.Almost all genetic mutation profiles detected in PLA could be seen in matched CSF samples in cohort two. With the driver genes, such as or have a higher detection rate in CSF compared to PLA. Moreover, the potential survival maker genes (6/12, 50%), (2/12, 17%), -amp (1/12, 8%), (1/12, 8%), and (1/12, 8%) were unique to the CSF samples.

CONCLUSION

For NSCLC -LM patients, regardless of single intracranial progression or intracranial progression simultaneously with extracranial evolution, CSF is superior to matched PLA.