Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2024

 Evaluating the clinical utility of circulating cell-free DNA in endometrial cancer: A systematic scoping review (#209)

Eliza Macdonald 1 , Grace Rose 2 3 , David Simar 1 , Alexandra McCarthy 4 , Caroline Ford 5 , Kristina Warton 5 , Sandi Hayes 6 7 , Briana Clifford 1 8
  1. School of Health Sciences, UNSW, Sydney, New South Wales, Australia
  2. School of Health , University of the Sunshine Coast, Sunshine Coast, Queensland, Australia
  3. School of Human Movement and Nutrition Sciences, University of Queensland, St Lucia, Queensland, Australia
  4. Griffith Health Group, Griffith University , Gold Coast, Queensland, Australia
  5. School of Clinical Medicine, UNSW, Sydney, New South Wales, Australia
  6. Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia
  7. Cancer Council Queensland, Fortitude Valley, Queensland, Australia
  8. School of Nursing, Midwifery and Social Work, University of Queensland, St Lucia, Queensland, Australia

Background/aim

Elevated concentrations of circulating cell free DNA (cfDNA) and circulating tumour DNA (ctDNA) have been identified in individuals with cancer. cfDNA is under investigation as a biomarker of clinical significance across the endometrial cancer (EC) continuum, but data are limited. The aim of this systematic scoping review is to provide an overview of studies evaluating the utility of cfDNA in EC and to describe the landscape of future cfDNA research in this context.

Methods

The review was conducted in accordance with PRISMA Scoping Reviews Guidelines and prospectively registered on the Open Science Framework (DOI:https://doi.org/10.17605/OSF.IO/6BFE7). Research databases and trials registries were searched from inception using terms related to “Endometrial cancer” and “Cell-free DNA”.

Results

Seventy-three records (n=61 studies; n=12 trials registrations) were included. Cohorts were EC/uterine cancer (UC) (n=26/61) or mixed (n=35/61), containing 1->1300 with EC/UC.  cfDNA was evaluated for its utility in (1) EC diagnosis, (2) EC molecular profiling, (3) EC prognosis/risk of recurrence, and (4) monitoring EC disease status over time. cfDNA was isolated from blood (n=60), vaginal fluid (n=1), peritoneal wash (n=2), uterine lavage (n=1), and urine (n=1). cfDNA analysis included quantification and sequencing, typically using fluorescence-based, PCR-based, and/or next generation sequencing assays. ctDNA parameters (e.g. mutation status/burden; methylation status) demonstrated superior performance to cfDNA quantity alone, in diagnosis, profiling, prognostic risk, and longitudinal monitoring. Three studies accounted for health factors, observing higher cfDNA quantity with elevated BMI and hypertension, and no difference in methylation-based assay diagnostic accuracy according to BMI.

Conclusions

cfDNA testing has potential to revolutionise minimally invasive EC diagnosis, profiling, prognostic risk assessment, and monitoring.  Improving the performance of cfDNA tests and determining the influence of health/lifestyle factors on cfDNA is paramount to this. Suitably powered longitudinal studies evaluating cfDNA kinetics represent an opportunity to harness cfDNA in EC surveillance and disease risk modification.