Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2026

Circulating cell-free DNA dynamics in endometrial cancer, health, and exercise (146076)

Eliza R Macdonald 1 , Vivian Chiu 2 , Kristina Warton 3 , David Simar 1 , Alexandra L McCarthy 4 , Briana K Clifford 1
  1. School of Health Sciences, UNSW, Sydney, New South Wales, Australia
  2. Griffith Health Group, Griffith University , Gold Coast, Queensland, Australia
  3. School of Clinical Medicine, UNSW, Sydney, New South Wales, Australia
  4. College of Health and Enablement, Flinders University, Adelaide, SA, Australia

Background

Circulating cell-free DNA (cfDNA) is elevated in cancer and associated with cardiometabolic risk factors. Cardiometabolic disease and cardiovascular mortality are disproportionately prevalent among endometrial cancer (EC) survivors, necessitating strategies to better predict, prevent, and manage long-term health complications. Exercise potentially confers improvements in fitness, body composition, and metabolic function yet limited evidence showing effectiveness exists in EC. Accurate measurement of cfDNA could quantify health risk and provide insight into the health risk-modifying effects of exercise in EC.

Aims

To quantify cfDNA in EC and healthy controls (HC), identifying clinicodemographic variables associated with cfDNA and evaluate changes in cfDNA following exercise. To optimise direct-from-sample (DFS) qPCR, overcoming technical limitations of clinical plasma-based cfDNA quantification.

Methods

EC survivors were recruited to the ACUMEN 12-week exercise intervention (ACTRN12621000050853). Plasma was collected at baseline(T0), post-intervention(T1) and follow-up(T2). HC plasma was sourced from a biobank(T0). cfDNA was quantified using qPCR targeting ALU-115 and ALU-247 repetitive elements. Optimisation experiments were performed to mitigate inhibition and maximise accuracy of DFS qPCR. Analysis used linear regression/mixed-effects models. Contrasts presented as geometric mean ratios (GMR)[95%CI].

Results

DFS qPCR performed optimally with 0.02μL plasma/reaction and additional carrier DNA (2ng ssDNA/reaction). At T0 (n(EC)=27; n(HC)=30) there was no association between total cfDNA and cohort (GMR HC/EC=0.9[0.67, 1.24], p=0.563). Within EC, univariate models showed cfDNA quantity was positively associated with BMI, waist circumference, age, fat mass, c-reactive protein and insulin, and negatively associated with fitness and fat-free mass. Adjusted model comparison revealed a significant exercise intervention effect (χ2(2)=27.3, p<0.001), with control participants showing greater increases in cfDNA between T1/T0 (difference-in-differences GMR(exercise/control)=0.8[0.7, 1.0], p=0.04) and T2/T1 (difference-in-differences GMR(exercise/control)=1.4[1.1, 1.6], p=0.024).

Conclusions

In EC survivorship, cardiometabolic risk, rather than cancer history, is associated with cfDNA quantity. Suitably powered longitudinal trials interrogating cfDNA source/content are required to examine exercise-related health risk modification after EC.