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. 2023 Oct;30(11):6652-6660.
doi: 10.1245/s10434-023-13701-2. Epub 2023 Jun 11.

Peritoneal Cell-Free Tumor DNA is a Biomarker of Locoregional and Peritoneal Recurrence in Resected Pancreatic Ductal Adenocarcinomas

Katie M Leick  1 , Ann Tomanek-Chalkley  1 , Kristen L Coleman  2 , Carlos H F Chan  3   4
Affiliations

Peritoneal Cell-Free Tumor DNA is a Biomarker of Locoregional and Peritoneal Recurrence in Resected Pancreatic Ductal Adenocarcinomas

Katie M Leick et al. Ann Surg Oncol. 2023 Oct.

Abstract

Background: Recurrence after curative-intent pancreatectomy for pancreatic ductal adenocarcinomas (PDAC) is quite frequent with locoregional and peritoneal recurrence in about one-third of cases. We hypothesize that peritoneal cell-free tumor DNA (ptDNA) present in the intraoperative peritoneal lavage (PL) fluid may be used as a predictive biomarker of locoregional and peritoneal recurrence.

Patients and methods: Under institutional review board (IRB)-approved protocol, pre- and postresection PL fluids were collected from PDAC patients undergoing curative-intent pancreatectomy. PL fluids from PDAC patients with pathologically proven peritoneal metastasis were also collected as positive controls. Cell-free DNA was extracted from PL fluids. Droplet digital PCR (ddPCR) was performed using ddPCR KRAS G12/G13 screening kit. Recurrence-free survival (RFS) based on KRAS-mutant ptDNA level was determined using Kaplan-Meier methods.

Results: KRAS-mutant ptDNA was detected in PL fluids from all PDAC patients. KRAS-mutant ptDNA was detected in 11/21 (52%) preresection and 15/18 (83%) postresection PL fluid samples. With a median follow-up of 23.6 months, 12 patients developed recurrence (8 locoregional/peritoneal recurrence, 9 pulmonary/hepatic recurrence); 5/8 (63%) and 6/6 (100%) patients with mutant allele frequency (MAF) of > 0.10% in pre- and postresection PL fluids, respectively, developed recurrence. Using a cutoff value of 0.10% MAF, the presence of KRAS-mutant ptDNA in postresection PL fluid predicted a significantly shortened time to locoregional and peritoneal recurrence (median RFS of 8.9 months versus not reached, P = 0.003).

Conclusions: This study suggests that ptDNA in postresection PL fluids may be a useful biomarker to predict locoregional and peritoneal recurrence in resected PDAC patients.

Keywords: Cell-free tumor DNA; Droplet digital PCR; KRAS mutation; Mutant allele frequency; Pancreatic cancer; Peritoneal metastasis.

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