Background: Gastroesophageal cancers commonly spread to the peritoneum. Peritoneal metastasis significantly alters patient prognosis and treatment-intent. Currently, our methods of peritoneal staging are inaccurate (1). 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 (2). We aim to develop and test a tumour-informed platform for ptDNA detection and validate its sensitivity and specificity against pathologically detectable peritoneal micro-metastases.
Methods: For this pilot study, peritoneal lavage fluid were collected at staging laparoscopy from 15 patients with gastroesophageal cancer. Cytology and peritoneal metastases (where clinically detectable) were confirmed by histopathology. A tumor-informed ptDNA testing was performed via whole-genome sequencing of tumor tissue and buffy coat to identify somatic variants for each patient, followed by tracking of up to 96 variants in each patient’s peritoneal fluid.
Results: Five out of 15 patients were either cytology positive or had macroscopic peritoneal disease and ptDNA was detectable in all 5 cases. Additionally, out of the 10 cytology-negative patients without macroscopic peritoneal disease, ptDNA positivity was detected in 6 patients prior to commencing neoadjuvant chemotherapy or surgery. Two of these 6 patients demonstrated radiological evidence of recurrence at 15- and 18-months follow-up respectively.
Conclusions: This pilot study demonstrates that a tumor-informed ptDNA detection platform is feasible and potentially more sensitive than peritoneal lavage cytology in gastroesophageal cancer. To further validate the clinical utility of ptDNA we are proceeding to a multi-center prospective cohort study.