Abstract 1063P
Background
Leptomeningeal metastases occurred in more than 3% of patients diagnosed with NSCLC, resulting in poor clinical outcomes. The cerebrospinal fluid (CSF) was a direct liquid biopsy for pathological diagnosis of leptomeningeal metastases. However, traditional clinical methods of detecting tumor cells in CSF showed limited sensitivity. Meanwhile, the unique genomic aberrations of leptomeningeal metastases remained unclear.
Methods
The prospective study plans to enroll 50 NSCLC patients diagnosed with leptomeningeal metastases. In the pilot study, 13 patients were enrolled and CSF samples were collected after diagnosis of metastases. Among them, PBMC samples were collected from 11 patients. PredicineCNB, a low-pass whole-genome sequencing (LP-WGS) assay, was performed to identify copy number variations and ctDNA fractions in CSF samples from all 13 patients. Furthermore, PredicineWES+, a boosted whole exon sequencing assay, was performed on paired CSF and PBMC samples from 11 patients.
Results
ctDNA fractions were identified in all 13 CSF samples through PredicineCNB assay. Gene copy variants related to NSCLC were also detected such as copy gain of EGFR(7pts), BRAF(5pts), MET(5pts), KRAS(2pts), ERBB2(2pts), ROS1(2pts), ALK(1pts) and copy loss of RB1(4pts), PTEN(2pts), TP53(1pts). The whole-exome sequencing results on 11 CSF samples with paired PBMC reference identified 1493 somatic variants, among which 97 variants were previously reported as possibly pathogenic by the public clinical database. For NSCLC-specific biomarkers, 7 out of 11 patients carried EGFR variants including 3 exon19del incidents, 1 exon20ins incident, 1 L858R mutation, and other gain-of-function mutations. The whole-exome sequencing test of CSF also identified an EML4-ALK fusion incident in 1 patient.
Conclusions
This study demonstrated the technical feasibility of analyzing genome-wide copy number variations and somatic variants using CSF samples from patients with NSCLC leptomeningeal metastases. Furthermore, this study revealed the comprehensive mutational landscape of NSCLC leptomeningeal metastases, providing novel biomarkers for clinical diagnosis and drug resistance mechanism study in NSCLC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Henan Cancer Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.