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Dynamic Tumor in Situ Fluid Circulating Tumor DNA Postsurgery Effectively Predicts Recurrence and Clinical Benefits for Glioblastomas

Year: 2025

Type: article

Abstract: BACKGROUND AND OBJECTIVES: Glioblastoma (GBM) recurrence after surgery remains a significant clinical challenge because of limited early detection methods and effective molecular markers. This study investigates the potential of dynamic tumor in situ fluid circulating tumor DNA (TISF-ctDNA) as a tool for monitoring molecular residual disease and evaluating treatment efficacy in postsurgical patients with GBM. METHODS: In this prospective cohort study, 75 resectable glioma patients were enrolled between October 2019 to June 2023. Primary tumor tissues and postsurgical TISF samples were collected, along with cranial imaging. TISF-ctDNA was identified through targeted next-generation sequencing, with positivity defined by the presence of one or more variants in the TISF matching those of the primary tumors or an increase of ≥10 single-nucleotide variants across consecutive assessments. RESULTS: TISF-ctDNA positivity was identified in 62.2% of patients in the early postsurgical period, indicating a high prevalence of molecular residual disease. Patients with positive TISF-ctDNA showed a significantly higher risk of recurrence (hazard ratio 2.512, 95% CI 1.264-4.993, P = .0054). Conversion to TISF-ctDNA negativity post-treatment was associated with improved overall survival, highlighting its role in evaluating treatment response. Multivariate analysis revealed that TISF-ctDNA positivity was an independent predictor of progression-free survival during adjuvant therapy, with high predictive accuracy (sensitivity 86.2%, specificity 100%). Importantly, TISF-ctDNA positivity preceded imaging signs of recurrence by a median of 71 days. In this study, no significant impact of specific tumor markers in each subcohort (EGFR, TP53, PTEN, NF1) on progression-free survival or overall survival was observed. CONCLUSION: TISF-ctDNA is a promising biomarker for monitoring GBM recurrence and evaluating clinical benefit. It provides insight into tumor genomic evolution and identifies patients who may benefit from adjuvant chemotherapy. TISF-ctDNA positivity is a robust prognostic indicator for patient outcomes and a marker for molecular recurrence after frontline therapy.

Source: Neurosurgery

DOI: 10.1227/neu.0000000000003384