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Updated: May 24, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Dynamic Tumor in Situ Fluid Circulating Tumor DNA Postsurgery Effectively Predicts Recurrence and Clinical Benefits
Jiubing Zhang1,2,3, Guanzheng Liu1,2,3, Dayang Wang2,3,4
1Department of Neurosurgery, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou , China.
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.
