Abstract
Purpose: Expediting the diagnosis of pancreatic ductal adenocarcinoma (PDAC) would benefit care management, especially for the start of treatments requiring histological evidence. This study evaluated the combined diagnostic performance of circulating biomarkers obtained by peripheral and portal blood liquid biopsy in patients with resectable PDAC. Experimental design: Liquid biopsies were performed in a prospective translational clinical trial (PANC-CTC #NCT03032913) including 22 patients with resectable PDAC and 28 noncancer controls from February to November 2017. Circulating tumor cells (CTCs) were detected using the CellSearch® method or after RosetteSep® enrichment combined with CRISPR/Cas9-improved KRAS mutant alleles quantification by droplet digital PCR. CD63 bead-coupled Glypican-1 (GPC1)-positive exosomes were quantified by flow cytometry. Results: Liquid biopsies were positive in 7/22 (32%), 13/22 (59%), and 14/22 (64%) patients with CellSearch® or RosetteSep®-based CTC detection or GPC1-positive exosomes, respectively, in peripheral and/or portal blood. Liquid biopsy performance was improved in portal blood only with CellSearch®, reaching 45% of PDAC identification (5/11) versus 10% (2/22) in peripheral blood. Importantly, combining CTC and GPC1-positive-exosome detection displayed 100% of sensitivity and 80% of specificity, with a negative predictive value of 100%. High levels of GPC1+-exosomes and/or CTC presence were significantly correlated with progression-free survival and with overall survival when CTC clusters were found. Conclusion: This study is the first to evaluate combined CTC and exosome detection to diagnose resectable pancreatic cancers. Liquid biopsy combining several biomarkers could provide a rapid, reliable, noninvasive decision-making tool in early, potentially curable pancreatic cancer. Moreover, the prognostic value could select patients eligible for neoadjuvant treatment before surgery. This exploratory study deserves further validation.
Highlights
Whereas overall survival of pancreatic ductal adenocarcinoma (PDAC) is less than 10%, survival can reach around 20% when surgery is possible, giving the best chance to the patients [1]
Upfront surgery was performed for 32 patients for presumed PDAC without neo-adjuvant therapy (Figure 1)
Eight patients were excluded from the cancer group and switched to the control group after definitive pathology analysis, because of noninvasive intraductal papillary mucinous neoplasm (IPMN) diagnosis
Summary
Whereas overall survival of pancreatic ductal adenocarcinoma (PDAC) is less than 10%, survival can reach around 20% when surgery is possible, giving the best chance to the patients [1]. Conventional tissue biopsies show heterogeneous diagnostic performance because of the intrinsic nature of the tumors with low cellularity associated with high stromal content. These difficulties lead to noninformative analysis of the tumor and even to false-negative diagnosis, with a negative predictive value ranking between 33% and 85%. Overall, this test may be inconclusive or doubtful in up to 20% of cases [4]. The alternative circulating biomarkers, such as the serum protein markers CEA(carcinoembryonic antigen) and CA19.9, are used to monitor early recurrences, but their low sensitivity and specificity prevent any use as screening or diagnostic tools [5]
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