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

Daniel Pietrasz (1, 2, 3) , Nicolas Pécuchet (1) , Fanny Garlan (1) , Audrey Didelot (1) , Olivier Dubreuil (3) , Solène Doat (3) , Francoise Imbert-Bismut (3) , Mehdi Karoui (3, 2) , Jean-Christophe Vaillant (3, 2) , Valérie Taly (1) , Pierre Laurent-Puig (1) , Jean-Baptiste Bachet (1, 2, 3)

1 MEPPOT - U1147 - Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique
2 UPMC - Université Pierre et Marie Curie - Paris 6
3 CHU Pitié-Salpêtrière [AP-HP]

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

Mots clés: Pancreatic Adenocarcinoma; Circulating tumor DNA; Prognostic; KRAS; NGS; digital

Domaines: Cancer

Daniel Pietrasz, Nicolas Pécuchet, Fanny Garlan, Audrey Didelot, Olivier Dubreuil, et al.. Plasma Circulating Tumor DNA in Pancreatic Cancer Patients Is a Prognostic Marker. Clinical Cancer Research, 2016, 23, pp.116 - 123. ⟨10.1158/1078-0432.CCR-16-0806⟩. ⟨hal-01458933⟩