Cell-free DNA in plasma and ascites as a biomarker of bevacizumab response- a translational research sub-study of the REZOLVE (ANZGOG-1101) clinical trial

Bonnita Werner ¹, Katrin M Sjoquist ², David Espinoza ²

⁰Gynaecological Cancer Research Group, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.

Translational Oncology +

|

February 28, 2024

View abstract on PubMed

Summary

Cell-free DNA (cfDNA) in ascites and plasma of ovarian cancer patients offers valuable prognostic information. Higher tumor-derived cfDNA (ctDNA) in ascites correlates with shorter intervals between fluid drainage and poorer survival, highlighting its potential as a biomarker.

Area Of Science

Gynecologic Oncology
Molecular Diagnostics
Cancer Biomarkers

Background

Advanced ovarian cancer often involves ascites, a fluid accumulation.
Monitoring disease progression and treatment response is crucial for patient outcomes.
Cell-free DNA (cfDNA) in bodily fluids is an emerging area of cancer research.

Purpose Of The Study

To analyze cell-free DNA (cfDNA) in plasma and ascites of advanced ovarian cancer patients.
To assess the association of cfDNA biomarkers with clinical outcomes like paracentesis-free interval and overall survival.
To investigate the relationship between cfDNA and CA125 levels in patients receiving palliative intraperitoneal bevacizumab.

Main Methods

cfDNA was extracted from plasma and ascites samples from participants in the REZOLVE trial.
Methylation-specific PCR was used to quantify total cfDNA (Alu), tumor-derived cfDNA (ctDNA), and endothelium-derived cfDNA (ec-cfDNA).
Biomarker levels were correlated with clinical outcomes and CA125 levels.

Main Results

cfDNA was detected in all samples, with significantly higher yield in ascites than plasma.
Ascites showed a higher proportion of ctDNA, while plasma had a higher proportion of ec-cfDNA.
High ctDNA in ascites correlated with a shorter paracentesis-free interval (p=0.039), and ctDNA in plasma was linked to poorer survival (p=0.008).
A positive correlation was found between plasma ctDNA proportion and CA125 levels (p=0.012).

Conclusions

Plasma and ascites cfDNA provide sufficient material for biomarker analysis in ovarian cancer.
cfDNA biomarkers, particularly ctDNA proportion, show significant associations with clinical outcomes.
These findings support the consideration of cfDNA analysis in future ovarian cancer clinical trial designs.

Keywords:

Ascites Bevacizumab Biomarker Cell-free DNA Ovarian cancer