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
• DOI: 10.1158/1078-0432.ccr-16-0806

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. 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. 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). 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.