HPB P06 The clinical and molecular landscape of early onset pancreatic cancer

Abstract

Abstract Background The incidence of Pancreatic ductal adenocarcinoma (PC) is rising in the western world. There is a particularly concerning trend in the rapid increase in incidence of early onset PC (EOPC). The reason for this, and the implications of EOPC is not well understood. The aim of this study was to investigate the clinical outcomes of patients with EOPC and the molecular heterogeneity between EOPC and late onset disease. Methods Clinical, pathological and survival outcome data was obtained from 2 large independent prospective cohorts curated by the Australian Pancreatic Genome Initiative (APGI) and the West of Scotland pancreatic unit (Glasgow Royal Infirmary). Patients were categorised into 2 age groups, < 50 and >50 years at time of diagnosis. Clinicopathological and outcome data were compared between groups. Molecular data was obtained from the APGI’s contribution to the International Cancer Genome Consortium, this included transcriptomic, genomic and immunohistochemical data. Molecular subtypes, gene expression signatures, mutational signatures, and tumour microenvironment data was compared between groups. Results N=851 patients were identified and n=71 (8%) were < 50 years old. EOPC was associated with earlier recurrence (10.9 vs 14.2 months, P=0.011) and higher incidence of liver recurrence (50% vs 37%, P=0.031). There were no differences in validated clinicopathological variables. Despite an increased proportion of patients with EOPC receiving adjuvant chemotherapy (P=0.020), recurrence was earlier in those that completed > 3 cycles (12.6 vs 16.0 months, P=0.022). There is enrichment of the poor prognostic squamous (basal) subtype (42% vs 28%) in EOPC. There were no differences in the incidence of germline mutations to account for the early onset of disease. Conclusions EOPC appears to be increasing in incidence and is associated with earlier recurrence and more aggressive disease pattern. This appears to be associated with resistance to adjuvant chemotherapy and more aggressive, adverse molecular pathology. The onset of early disease cannot be explained by inherited genomic aberrations. Ongoing mutation signature, gene expression and microenvironmental data analysis will be presented upon acceptance of this abstract.