Longitudinal Glioma Monitoring via Cerebrospinal Fluid Cell-Free DNA.

Area of Science:

• Neuro-oncology
• Molecular Diagnostics
• Liquid Biopsy

Background:

• Current glioma response assessment methods are limited.
• Molecular profiling of cerebrospinal fluid (CSF) offers a potential avenue for improved assessment.
• Longitudinal monitoring can provide dynamic insights into disease course.

Purpose of the Study:

• To assess the technical and clinical feasibility of molecular profiling using longitudinal intracranial CSF in glioma patients.
• To evaluate the utility of cell-free DNA (cfDNA) analysis in CSF for tracking glioma response.

Main Methods:

• Longitudinal intracranial CSF collection from adult glioma patients via Ommaya reservoirs or shunts.
• Extraction and analysis of cell-free DNA (cfDNA) using cancer variant profiling and low-pass whole-genome sequencing.
• Monitoring of tumor-associated variant allelic frequencies (VAF) and copy-number burden in CSF samples.

Main Results:

• Sufficient cfDNA for testing was obtained from 87.2% of 47 CSF samples.
• Decreased cfDNA VAF correlated with response to treatment and increased with progression.
• Copy-number burden changes in CSF reflected treatment response and disease progression.
• Correlation observed between decreasing IDH1 VAF and CSF D-2-hydroxyglutarate levels in IDH-mutant gliomas.

Conclusions:

• Longitudinal intracranial CSF cfDNA collection and analysis are technically feasible in glioma patients.
• This approach shows promise for monitoring glioma treatment response and disease progression.
• Further research is needed to address remaining questions and challenges before widespread clinical deployment.