The clinical and molecular landscape of early onset pancreatic cancer (V体育官网)

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 clinical 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. Materials and Methods: Clinical, pathological and survival outcome data were 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. Of these, n = 71 (8%) were < 50 years old. EOPC was associated with significantly earlier recurrence following surgery (median disease-free survival (DFS) 10. 9 vs 14. 2 months, P = 0. 011) and higher incidence of liver recurrence post-operatively (50% vs 37%, P = 0. 031). There was a trend towards shorter overall survival (median 19. 9 vs 23. 8 months, P = 0. 117). There were no differences in validated clinicopathological variables, including resection margin, grade, pathological T- and N- stage, vascular and perineural invasion, or location of primary, to account for the shorter DFS in the EOPC group. Despite an increased proportion of patients with EOPC receiving adjuvant chemotherapy (75% vs 61%, P = 0. 020), DFS was significantly worse in those that completed ≥ 3 cycles (DFS 12. 6 vs 16. 0 months, P = 0. 022). In the transcriptomic analysis, there is enrichment of the poor prognostic squamous (basal) subtype (42% vs 28%) in EOPC when compared with later onset PC. There were no differences in the incidence of germline mutations to account for the early onset of disease VSports app下载. Further molecular and microenvironmental analyses are ongoing. Conclusions: EOPC appears to be increasing in incidence and is associated with earlier disease recurrence and a 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 analysis of mutational signature, gene expression and microenvironmental data will be presented upon acceptance of this abstract.