Genetic Alterations Predict Long-Term Survival in Ductal Adenocarcinoma of the Pancreatic Head.

Background: Survival of patients with adenocarcinoma of the pancreas (PDAC) is poor and has remained almost unchanged over the past decades. The genomic landscape of PDAC has been characterized in recent years. The aim of this study was to identify a genetic profile as a possible predictor of prolonged survival in order to tailor therapy for PDAC patients.

Methods: Panel next generation sequencing (NGS) and immunohistochemistry (IHC) were performed on paraffin-embedded tumor tissues from curatively treated PDAC patients. Tumor slides were re-evaluated with a focus on the histomorphology. Patients were subgrouped according to short and long overall (<4 years/>4 years) and disease-free (<2 years/>2 years) survival.

Results: Thirty-nine patients were included in the study. Clinicopathological staging variables as well as the histomorphological subgroups were homogenously distributed between short- and long-term overall and disease-free survivors. In survival analysis, patients with the G12D mutation and patients with nonsense and splice-site mutations had a significantly worse overall survival (OS) and disease-free survival (DFS). Patients with long-term OS and DFS showed no G12D, no nonsense or splice-site mutations. Rare Q61H/D57N mutations were only found in long-term survivors. The allele frequency rate of and mutations in tumor cells was significantly higher in short-term disease-free survivors and overall survivors, respectively.

Conclusions: NGS of PDAC revealed significant differences in survival outcome in a patient collective with homogenously distributed clinicopathological variables. Further multi-institutional studies are warranted to identify more long-term survivors to detect genetic differences suitable for targeted therapy.