Plasma Circulating Tumor DNA in Pancreatic Cancer Patients Is a Prognostic Marker

• Published in: Clinical cancer research Vol. 23; no. 1; pp. 116 - 123
• Main Authors: Pietrasz, Daniel, Pécuchet, Nicolas, Garlan, Fanny, Didelot, Audrey, Dubreuil, Olivier, Doat, Solène, Imbert-Bismut, Francoise, Karoui, Mehdi, Vaillant, Jean-Christophe, Taly, Valérie, Laurent-Puig, Pierre, Bachet, Jean-Baptiste
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 01.01.2017; American Association for Cancer Research
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Blood; Cancer; Circulating Tumor DNA; Deoxyribonucleic acid; DNA; Experimental design; Feasibility studies; Female; High-Throughput Nucleotide Sequencing; Humans; Life Sciences; Male; Medical prognosis; Metastases; Middle Aged; Mutation; Neoplasm Grading; Neoplasm Staging; Neoplastic Cells, Circulating; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - surgery; Patients; Prognosis; Proportional Hazards Models; Surgery; Survival; Tissues; digital; KRAS; Pancreatic Adenocarcinoma; NGS; Circulating tumor DNA; Prognostic
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-16-0806

Purpose: Despite recent therapeutic advances, prognosis of patients with pancreatic adenocarcinoma remains poor. Analyses from tumor tissues present limitations; identification of informative marker from blood might be a promising alternative. The aim of this study was to assess the feasibility and the prognostic value of circulating tumor DNA (ctDNA) in pancreatic adenocarcinoma. Experimental Design: From 2011 to 2015, blood samples were prospectively collected from all consecutive patients with pancreatic adenocarcinoma treated in our center. Identification of ctDNA was done with next-generation sequencing targeted on referenced mutations in pancreatic adenocarcinoma and with picoliter droplet digital PCR. Results: A total of 135 patients with resectable (n = 31; 23%), locally advanced (n = 36; 27%), or metastatic (n = 68; 50%) pancreatic adenocarcinoma were included. In patients with advanced pancreatic adenocarcinoma (n = 104), 48% (n = 50) had ctDNA detectable with a median mutation allelic frequency (MAF) of 6.1%. The presence of ctDNA was strongly correlated with poor overall survival (OS; 6.5 vs. 19.0 months; P < 0.001) in univariate and multivariate analyses (HR = 1.96; P = 0.007). To evaluate the impact of ctDNA level, patients were grouped according to MAF tertiles: OS were 18.9, 7.8, and 4.9 months (P < 0.001). Among patients who had curative intent resection (n = 31), 6 had ctDNA detectable after surgery, with an MAF of 4.4%. The presence of ctDNA was associated with a shorter disease-free survival (4.6 vs.17.6 months; P = 0.03) and shorter OS (19.3 vs. 32.2 months; P = 0.027). Conclusions: ctDNA is an independent prognostic marker in advanced pancreatic adenocarcinoma. Furthermore, it arises as an indicator of shorter disease-free survival in resected patients when detected after surgery. Clin Cancer Res; 23(1); 116–23. ©2016 AACR.