Research AppraisalSystematic Review

Utilization of next generation sequencing from glioma patient liquid biopsy to determine survival prognostics: A systematic review

GeneSugiarto, Christine, Haryanti, Fitri, Purwanto, Ibnu et al.5 June 2026DOI

Clinical Snapshot

50CEBM
Evidence: WeakSystematic Review

PICO Framework

P — PopulationPatients with glioma (malignant central nervous system tumours)
I — InterventionNext generation sequencing (NGS) analysis of circulating tumour DNA (ctDNA) or cell-free DNA (cfDNA) from liquid biopsy samples
C — ComparatorBaseline ctDNA/cfDNA concentrations or conventional prognostic methods
O — OutcomesProgression-free survival (PFS), overall survival (OS), and ctDNA/cfDNA concentration correlation with tumour grading and progression

Bottom Line

This systematic review examines NGS-based liquid biopsy for glioma prognosis across 14 studies involving 663 patients. While higher ctDNA concentrations appear associated with worse progression-free and overall survival, the evidence remains insufficient for clinical implementation. The review identifies significant methodological heterogeneity, with highly variable patient grouping and lack of standardised ctDNA cut-off values. The authors appropriately conclude that further studies with standardised methodologies are needed before this technology can reliably inform clinical decision-making. Currently, liquid biopsy for glioma prognosis should be considered investigational rather than routine practice. Clinicians should continue relying on established prognostic factors including histological grading, molecular markers (IDH mutation, 1p/19q codeletion), and imaging characteristics until more robust evidence emerges.

Evidence: Weak

Key Findings

  • P Value: Not reported

  • Effect Size: Not quantified - qualitative assessment only

  • Primary Outcome: Correlation between ctDNA concentration and survival outcomes (PFS and OS)

  • Nnt Or Sensitivity: Higher ctDNA concentrations associated with worse prognosis, but no standardised cut-off values established

  • Confidence Interval: Not reported

Clinical Application

Limited by lack of standardised ctDNA cut-off values and variable methodologies across studies NGS technology available through major pathology services, but liquid biopsy for glioma prognosis not yet established in NPAAC guidelines or covered by PBS for this indication Patients with confirmed glioma requiring prognostic assessment

Abstract

Glioma is a malignant cancer that affects the central nervous system. Early detection of glioma is still difficult due to the hard-to-reach location of the cancer. The use of next generation sequencing is one of the new developments that can be used for diagnosis, however the use of this modality for prognosis is still rarely discussed. This systematic review aims to determine the benefits of using next generation sequencing (NGS) on the assessment of ctDNA or cfDNA concentration, progression free survival (PFS), and overall survival (OS). This systematic review was made using data from six databases, namely PubMed, PMC, ProQuest, Google Schoolar, ScienceDirect, and SCOPUS, and was compiled based on guidelines from PRISMA. Fourteen studies were included in this systematic review with a total of 663 glioma patients. The results of ctDNA measurements generated through the NGS method with liquid biopsy samples show that the higher the grading and sampling when the tumor progresses can increase the ctDNA value. When assessing ctDNA concentrations at baseline when samples were taken, most studies showed a worse prognosis for PFS and OS survival time. However, the grouping of patients in the current studies is still highly variable so further studies with standardized ctDNA cut off values are needed for more precise determination of prognosis.

References

  1. 1.Sugiarto, C., Haryanti, F., Purwanto, I., Choridah, L., Malueka, R. G., Dwianingsih, E. K., & Andriani, R. (2026). Utilization of next generation sequencing from glioma patient liquid biopsy to determine survival prognostics: A systematic review. Gene, 150103. https://doi.org/10.1016/j.gene.2026.150103
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