Poster Presentation 36th Lorne Cancer Conference 2024

Peritoneal tumour DNA in gastroesophageal cancer – metanalysis and a pilot study   (#233)

Zexi Allan 1 , Jeanne Tie 1 , Bert Vogelstein 2 , Niall Tebbutt 3 , Nicholas Clemons 1 , David Liu 1
  1. Peter MacCallum Cancer centre, Melbourne, VIC, Australia
  2. Program in Human Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  3. Department of Medical Oncology, Austin Health, Melbourne, VIC, Australia

Aims: To develop a tumour-informed platform for peritoneal tumour DNA (ptDNA) detection and validate its sensitivity and specificity against pathologically detectable peritoneal micro-metastases.

Background: Gastroesophageal cancers commonly spread to the peritoneum. Peritoneal disease significantly alters patient prognosis and treatment-intent (1). Currently, our methods of peritoneal disease staging are inaccurate (2). Peritoneal tumour DNA (ptDNA) is tumour-derived DNA detectable in peritoneal lavage fluid. ptDNA-positivity may indicate peritoneal micro-metastasis and may be more sensitive than cytology in staging the peritoneum (3).

Methods: We meta-analysed 6 studies of gastric cancer containing quantitative data relating to ptDNA post searching PubMed, EMBASE, Scopus and Web-of-Science databases.

For the pilot study, tumour biopsies, blood samples and peritoneal lavage fluid were collected at staging laparoscopy from 13 prospectively recruited patients with gastroesophageal cancer. Cytology and peritoneal disease status were confirmed by histopathology. ptDNA status was determined via whole-exome sequencing of the peritoneal lavage fluid.

Results: Our metanalysis showed that overall, ptDNA detected cytology-positive cases with a sensitivity and specificity of 85.2% (95% CI 66.5-100.0%) and 91.5% (95% CI 86.5-96.6%), respectively. Additionally, ptDNA was detected in 54 (8.5%) of 634 cytology-negative patients. Importantly, ptDNA-positivity predicted an increased risk of peritoneal-specific metastasis (RR 13.81, 95% CI 8.11-23.53) and reduced 3-year progression-free (RR 5.37, 95% CI 1.39-20.74) and overall (HR 4.13, 95% CI 1.51-11.32) survival.

In the pilot study, 4 out of the 13 prospectively recruited patients tested positive for cytology, and all those cases had detectable ptDNA. In addition, ptDNA was detected in one patient who was both cytology and peritoneal disease negative. 

Conclusions: Our pilot study demonstrates that a tumour-informed platform of ptDNA detection is feasible and of high sensitivity and specificity against proven peritoneal micro-metastases. To further validate the clinical utility of ptDNA in staging the peritoneum, larger prospective studies with survival outcomes are needed.

  1. Rice TW, Patil DT, Blackstone EH. 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice. Annals of cardiothoracic surgery. Mar 2017;6(2):119-130.
  2. Leake PA, Cardoso R, Seevaratnam R, et al. A systematic review of the accuracy and utility of peritoneal cytology in patients with gastric cancer. Gastric Cancer. Sep 2012;15 Suppl 1:S27-37.
  3. Allan, Z., Witts, S., Tie, J. et al. The prognostic impact of peritoneal tumour DNA in gastrointestinal and gynaecological malignancies: a systematic review. Br J Cancer (2023). https://doi.org/10.1038/s41416-023-02424-6