Gliomas are the most common primary brain tumors, but there are currently many limitations for the implementation of liquid biopsy in this disease. Cerebrospinal fluid (CSF) is emerging as the most reliable reservoir for ctDNA analysis, although evidence is still limited.
Prospective study of patients with gliomas diagnosed at Hospital Clinico Universitario San Carlos and Hospital Universitario La Paz (Madrid, Spain). High throughput next generation sequencing (NGS) using a customized gene panel (Illumina, Inc.) of 8 genes (IDH1, IDH2, ATRX, TP53, PTEN, PIK3CA, EGFR, BRAF) was used in paired CSF and FFPE and/or fresh tumor samples, and run in an Illumina Miseq instrument (Illumina, Inc.). Only confirmed pathogenic mutations were considered as valid and are reported here. Mutation concordance occurred when the same pathogenic gene variants were detected in tumor and CSF.
Between February 2017 and March 2020, 31 glioma patients (pts) were enrolled in which 2-5 ml of CSF were collected intraoperatively prior to surgical manipulation of the tumor. M:F ratio: 22:9. Median age 51 (Min-Max: 20-78). CSF collected at new diagnosis (n=22); relapse (n=9). WHO 5th Ed: IDHMUT astrocytoma (n=9), IDHMUT oligodendroglioma (n=6), IDHWT glioblastoma (n=16). CSF-ctDNA-positive: 18/31 (58%). CSF-ctDNA-negative: 13/31 (42%). No. of mutations in CSF: 1 (9/18), 2 (7/18), 3 (2/18). Frequency of CSF-ctDNA mutated genes: EGFR (8/18: 44%), PTEN (7/18: 39%), TP53 (6/18: 33%), IDH1 (4/18: 22%), PIK3CA (4/18: 22%). Tumor-CSF mutation concordance: 15/18 (83%). After a median follow-up since CSF collection of 20 months (m) (Min-Max: 0-57), median OS was not reached (NR) (95%CI NR-NR). No correlation was found between detection of ctDNA in CSF and distance from closest CSF reservoir, tumor size or IDH status.
CSF is a reliable reservoir for ctDNA analyses in patients with gliomas. Larger, prospective studies should be conducted in order to refine the potential role of liquid biopsy in this disease.
Clinical trial identification
Legal entity responsible for the study
Study funded thanks to the BECA GEINO 2016 from Grupo Español de Investigación en Neuro-Oncología (GEINO).
S. Cabezas-Camarero: Financial Interests, Personal, Invited Speaker: BMS, Merck Serono, MSD; Financial Interests, Personal, Expert Testimony: MSD, BMS, Merck Serono; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Institutional, Funding: Merck Serono. All other authors have declared no conflicts of interest.