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Title: 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.
Epworth Authors: Ananda, Sumitra
Other Authors: Werner, Bonnita
Sjoquist, Katrin
Espinoza, David
Yip, Sonia
Chang, Garry
Cummins, Michelle
Mileshkin, Linda
Shannon, Catherine
Friedlander, Michael
Warton, Kristina
Ford, Caroline
Keywords: Ascites
Cell-free DNA
Ovarian cancer
Cancer Services Clinical Institute, Epworth HealthCare, Victoria, Australia
Issue Date: May-2024
Publisher: Elsevier
Citation: Transl Oncol . 2024 May:43:101914
Abstract: Objective: To investigate cell-free DNA (cfDNA) in plasma and ascites and its association with clinical outcomes (paracentesis-free interval, overall survival) and CA125 level in participants with advanced ovarian cancer, treated with palliative intraperitoneal bevacizumab to delay re-accumulation of ascites. Methods: cfDNA was extracted from 0.3 to 1 mL samples from 20/24 participants of the REZOLVE trial. Standard and methylation-specific PCRs were performed to measure 3 biomarkers: total cfDNA (Alu), tumour-derived cfDNA (ctDNA, methylated IFFO1 promoter) and endothelium-derived cfDNA (ec-cfDNA, unmethylated CDH5 promoter). Values were correlated to clinical outcomes. Results: cfDNA was detected in all samples, with higher yield in ascites (mean 669 ng/mL) than plasma (mean 75 ng/mL, p < 0.0001). Ascites had a higher ctDNA proportion than plasma (74 % vs. 20 %, p < 0.0001) and plasma had a higher ec-cfDNA proportion than ascites (24 % vs. 16 %, p < 0.002). High ctDNA proportion (>75 %) in ascites was associated with a significantly shorter paracentesis-free interval (median interval 47.5 versus 84 days, hazard ratio (HR) 2.21, 95 % confidence interval (CI) 0.85 to 5.73, p = 0.039) and ctDNA presence in plasma was unfavourable for survival (median survival 56 versus 242 days, HR 3.21, 95 % CI 1.15 to 9.00, p = 0.008). A significant positive correlation was observed between ctDNA proportion in plasma and CA125 level (p = 0.012). No significant difference in total cfDNA, ctDNA nor ec-cfDNA was observed between participants who were responders versus non-responders. Conclusion: Sufficient cfDNA was detected in both plasma and ascites to study three biomarkers. These samples can provide useful information and should be considered in the design of future ovarian cancer trials.
DOI: doi: 10.1016/j.tranon.2024.101914
PubMed URL:
ISSN: 1936-5233
Journal Title: Translational Oncology
Type: Journal Article
Affiliated Organisations: Gynaecological Cancer Research Group, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.
National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.
Peter MacCallum Cancer Centre, Melbourne, Australia.
Western Health, Furlong Road, St Albans, Australia.
Department of Medicine, Western Health, University of Melbourne, Melbourne, Australia.
Mater Cancer Care Centre, South Brisbane, Australia.
Prince of Wales Hospital, Sydney, Australia.
School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.
Type of Clinical Study or Trial: Cohort Study
Appears in Collections:Cancer Services

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