Liquid biopsy for evaluating mutations and chromosomal aberrations in cerebrospinal fluid from patients with primary or metastatic CNS tumors.

Background: Cytopathology analysis of cerebrospinal fluid (CSF) is limited in detecting tumors in patients with suspected primary or metastatic central nervous system (CNS) malignancy. We investigated the use of CSF liquid biopsy (LBx) to detect neoplastic processes in the CNS. Methods: Cell-free DNA (cfDNA) from the CSF of patients with suspected metastatic (N = 106) or primary CNS (N = 23) tumors was deep sequenced using a 302-gene panel. Results: Four samples (3 %) (3 metastatic and 1 primary) failed sequencing quality control criteria. Metastatic tumor was confirmed in 84 (82 %) of the 103 patients suspected of metastatic tumor. Primary CNS tumor was confirmed in 11 of 22 (50 %) patients suspected of CNS tumor. Chromosomal abnormalities were detected in 55 samples (54 %). Germline mutations were detected in 23 (22 %) patients with metastatic tumors and in 1 (5 %) with a primary CNS tumor. Of the 29 patients with metastatic breast cancers, 2 (7 %) had mutations in ESR1 and 9 (31 %) had mutations in PIK3CA. Of the 21 patients with metastatic lung cancer, 9 (43 %) had EGFR mutations and 5 (24 %) had KRAS mutations. Upon comparing CSF LBx with peripheral blood LBx in 14 patients, 13 (93 %) showed only CHIP and one patient showed CNS primary tumor mutation. Serial samples from 14 patients demonstrate that CSF LBx can be used for monitoring therapy efficacy. Conclusions: LBx using CSF is clinically reliable and provides informative results in a substantial proportion of patients with metastatic CNS tumors and to a lesser degree in patients with primary CNS tumors.