Next-Generation Sequencing of Intraoperatively Acquired Cerebrospinal Fluid and Matched Tumor Tissue in Patients Undergoing Surgical Resection for Glioblastoma

PURPOSE:Because of tumor heterogeneity and sampling error, next-generation sequencing (NGS) of glioblastoma (GBM) tumors may provide an incomplete picture of the somatic mutational landscape. We hypothesized that simultaneous targeted NGS of matched tumor tissue and cerebrospinal fluid (CSF), obtained during craniotomy for resection of GBM, would lead to identification of clinically relevant variants not detected by tissue NGS alone. METHODS:We enrolled 50 patients undergoing resection of newly diagnosed (n = 15) or recurrent (n = 35) GBM. CSF was collected intraoperatively via the subarachnoid space (n = 25) or lateral ventricle (n = 25) and assayed by NGS using a hybrid capture liquid biopsy panel. Matched tumor tissue also underwent large panel hybrid capture NGS testing. RESULTS:CSF samples from 28 of 50 patients (56%) passed quality control metrics. At least one CSF variant was detected in 25 of 28 patients (89%), and 22 of 28 patients had matched tissue sequencing results available. In these 22 patients (primary analysis cohort), the median number of variants detected in CSF was higher than in tissue (3 v 2 variants, respectively; P = .0035), and 15 of 22 patients (68%) had ≥1 CSF variant not detected in matched tissue, including clinically relevant alterations in EGFR, PMS2, PIK3CA, and TP53. CONCLUSION:The addition of intraoperatively acquired CSF liquid biopsy to tissue NGS in patients with GBM may improve detection of clinically relevant variants, potentially improving selection of patients for clinical trials.