Peritoneal Cell-Free Tumor DNA is a Biomarker of Locoregional and Peritoneal Recurrence in Resected Pancreatic Ductal Adenocarcinomas
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 lavag...
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Veröffentlicht in: | Annals of surgical oncology 2023-10, Vol.30 (11), p.6652-6660 |
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Zusammenfassung: | 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. |
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ISSN: | 1068-9265 1534-4681 1534-4681 |
DOI: | 10.1245/s10434-023-13701-2 |