Abstract A049: Peritoneal tumor DNA as a prognostic biomarker in locally advanced gastroesophageal cancer: A pilot prospective cohort study
Authors: Zexi Allan, Yuxuan Wang, Jeanne Tie, Niall Tebbutt, Nicholas Clemons, Nickolas Papadopoulos, Kenneth Kinzler, Bert Vogelstein, David SH Liu
Journal: Clinical Cancer Research (2024)

Abstract Background: Gastroesophageal cancers commonly spread to the peritoneum. Peritoneal disease significantly alters patient prognosis and treatment-intent. Currently, peritoneal lavage cytology (PLC) is the method of choice for detecting peritoneal micro-metastasis within the peritoneum. Despite its pervasive use, PLC has a variable sensitivity of 10% - 80% in detecting peritoneal micro-metastasis in gastroesophageal cancers. Peritoneal tumor DNA (ptDNA) is tumor-derived DNA detectable in peritoneal lavage fluid. ptDNA-positivity may indicate peritoneal micro- metastasis and may be more sensitive than PLC in staging the peritoneum and predicting disease- free survival (DFS) and overall survival (OS). We aimed to develop and test a tumor-informed platform for ptDNA detection and validate its sensitivity and specificity against PLC. 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 patients, followed by tracking of up to 96 variants in each patient’s peritoneal fluid. Results: 5 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. Interestingly, one patient with macroscopic peritoneal disease tested negative for cytology. In this case, peritoneal lavage was carried out to the upper two abdominal quadrants only, and the pelvic deposit of disease was detected after the lavage had been completed. Despite a negative cytology result, ptDNA was detected using the same fluid sample, suggesting a higher sensitivity compared to PLC. Conclusions: This pilot study demonstrates that a tumor-informed ptDNA detection platform is feasible and potentially more sensitive than PLC in gastroesophageal cancer. To further validate the clinical utility of ptDNA we are proceeding to a multi-center prospective cohort study. Citation Format: Zexi Allan, Yuxuan Wang, Jeanne Tie, Niall Tebbutt, Nicholas Clemons, Nickolas Papadopoulos, Kenneth Kinzler, Bert Vogelstein, David SH Liu. Peritoneal tumor DNA as a prognostic biomarker in locally advanced gastroesophageal cancer: A pilot prospective cohort study [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A049.