307 Baseline Gut Microbiome Composition is Associated with Response to Neoadjuvant Chemotherapy in Pancreatic Cancer Patients

Abstract Aim The reasons underlying the variation to response to neoadjuvant chemotherapy (NAT) in pancreatic cancer (PC) remain poorly understood. The aim of this study was to compare the gut microbiome composition between PC patients who did (R) and did not (NR) respond to NAT. Method This prospective cohort study included PC patients who received at least three cycles of neoadjuvant FOLFIRINOX. NAT response was determined using biochemical (Ca19-9 levels) and radiological criteria. Shotgun metagenomic sequencing of DNA extracted from baseline stool samples was performed using the Oxford Nanopore PromethION platform. R and NR groups were compared using empirical Bayes statistics for differential expression. Results Among 20 consecutive PC patients, 14 received at least 3 cycles of NAT and 7 of these had a favourable response (50%). The abundance of species such as Akkermansia muciniphilia, previously associated with favourable response to chemotherapy for other cancer types, were significantly increased in the gut microbiome of R compared to NR (logFC+2.97, p=0.002). In contrast, bacterial species such as Bacteroides vulgatus, previously associated with poor response to irinotecan-containing chemotherapy agents, were significantly reduced in the baseline gut microbiome of R compared to NR (logFC-1.80, p=0.006). Baseline alpha and beta-diversity indices were not significantly different between the groups. Conclusions The baseline gut microbiome composition of patients with PC associates with response to NAT. Differences include species known to influence chemotherapy responses in other malignancy types. Optimisation of the gut microbiome may offer the potential to improve the clinical response to NAT in patients with this tumour of unmet need.