CNSC-04. CEREBROSPINAL FLUID-DERIVED CIRCULATING TUMOR DNA IS SUPERIOR TO PLASMA IN NSCLC PATIENTS WITH CNS PROGRESSION

Abstract

Abstract Introduction Central nervous system (CNS) metastases are devastating neurologic complications. However, the clinical value of cerebrospinal fluid (CSF) as liquid biopsy medium in EGFR-mutated or ALK-rearranged patients with brain metastases (BM) or leptomeningeal metastases (LM) remains unclear. Patients and Methods We retrospectively analyzed the gene map of 14/48 NSCLC-BM patients and 34/48 NSCLC-LM patients. Compare the clinical predictive value of CSF and matched plasma (PLA) for patients with single CNS progression (cohort 1) or intracranial progression simultaneously with extracranial disease progression (cohort 2). Circulating cell-free tumor DNA (ctDNA) in CSF and matched PLA underwent next-generation sequencing targeting 168 cancer-relevant genes. Results For patients with single CNS progression, the mutation rate of major driver genes is much higher than the rate in matched PLA. Besides, CSF also demonstrated higher levels of potential prognostic markers in comparison with matched PLA samples, showing EGFR-amp presented more than two times the rate compared to matched PLA, and the detection rate of TBX3, PTEN were almost double the rate in CSF than paired PLA samples. In addition, poor outcomes associated with makers including CDKN2A/B, PIK3CA/G, CDK4/6, and MET showed exclusively in CSF samples.Almost all mutations identified in the PLA could detect in matched CSF samples in NSCLC-LM patients with both intracranial and extracranial disease progression. In addition, detection rates of driver mutations, consisting of EGFR or ALK are much higher in CSF compared to matched PLA, and these potential survival marker genes like CDK4/6, CDKN2A/B, EGFR-amp, MET, and PIK3CA identified uniquely in CSF samples. Conclusion CSF is more comprehensive in genomic mutation profile than matched PLA in NSCLC -LM regardless of single intracranial progression or intracranial progression simultaneously with extracranial evolution.