Abstract
We reported unique molecular features of cerebrospinal fluid (CSF) of nonsmall cell lung cancer (NSCLC) patients with leptomeningeal metastasis (LM), suggesting establishing CSF as a better liquid biopsy in clinical practices. We performed next-generation panel sequencing of primary tumor tissue, plasma, and CSF from 131 NSCLC patients with LM and observed high somatic copy number variations (CNV) in CSF of NSCLC patients with LM. The status of EGFR-activating mutations was highly concordant between CSF, plasma, and primary tumors. ALK translocation was detected in 8.3% of tumor tissues but only 2.4% in CSF and 2.7% in plasma. Others such as ROS1 rearrangement, RET fusion, HER2 mutation, NTRK1 fusion, and BRAF V600E mutation were detected in 7.9% of CSF and 11.1% of tumor tissues but only 4% in plasma. Our study has shed light on the unique genomic variations of CSF and demonstrated that CSF might represent better liquid biopsy for NSCLC patients with LM.
Highlights
The incidence of leptomeningeal metastasis (LM) of nonsmall cell lung cancer (NSCLC) is increasing due to improved treatment and prolonged survival of NSCLC patients [1, 2]
Anaplastic lymphoma kinase (ALK) inhibitor has extended the survival of NSCLC patients with ALK translocation [13]
Approximately 10 ml of cerebrospinal fluid (CSF) was collected via lumbar puncture for cytology examination and next-generation sequencing (NGS), and 10 ml of plasma was collected for NGS
Summary
The incidence of leptomeningeal metastasis (LM) of nonsmall cell lung cancer (NSCLC) is increasing due to improved treatment and prolonged survival of NSCLC patients [1, 2]. Anaplastic lymphoma kinase (ALK) inhibitor has extended the survival of NSCLC patients with ALK translocation [13]. Other actionable targets such as c-ros oncogene 1 (ROS1), BRAF V600E, and neurotrophic tyrosine receptor kinase (NTRK) have tyrosine kinase inhibitors other than chemotherapy alone [14,15,16]. Tissue biopsy was regarded as the golden standard of molecular classification and was critical in decision-making concerning treatment for advanced NSCLC patients [17]. It is a clinical challenge to collect tumor tissue for genotyping, as the invasive and time-consuming procedures may be risky to these advanced-stage NSCLC patients [18]. For NSCLC patients with LM, a small number of patients has been studied and the genotyping of CSF for NSCLC with LM has been largely unknown [2, 20]
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