Cerebrospinal fluid cfDNA-based molecular assessment of resection extent and prognosis in glioma

Abstract Gliomas, the most common brain tumors, present significant challenges in treatment, particularly glioblastoma multiforme (GBM), due to their infiltrative nature and difficulty in achieving gross total resection (GTR). Accurate assessment of surgical resection extent is critical for patient prognosis and survival. This study investigates the utility of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) as a quantitative biomarker for evaluating glioma resection extent and patient prognosis. We employed next-generation sequencing (NGS) to profile genomic alterations in both tumor DNA and CSF ctDNA collected pre- and post-operatively. A high concordance rate (83.50%) between CSF ctDNA and tumor tissue was found, particularly for key somatic mutations such as TERT, TP53, PTEN and IDH1. Post-operative ctDNA analysis revealed a significant reduction in mean mutant allele frequency (MAF) and tumor mutational burden (TMB). Apart from non-GTR and multiple lesions, patients who exhibited a ≥ 90% reduction in mean MAF or in the MAF of driver mutations post-surgery demonstrated significantly improved overall survival (OS). These findings suggest that CSF ctDNA effectively represents the genetic profile of gliomas and serves as a sensitive measure for surgical resection efficacy and patient prognosis, highlighting its potential as a non-invasive biomarker for enhancing post-operative management in glioma patients.