1511P - The influence of intratumoral bacteria and peri-operative antibiotic treatment on the outcome of resected pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy

Background

Gemcitabine-based adjuvant chemotherapy (aGC) is a therapeutic mainstay after surgery for pancreatic ductal adenocarcinoma (PDAC), but relevant efficacy predictors are still lacking. Intratumoral gram-negative bacteria can suppress response to aGC. We assessed the effect of intratumoral bacterial colonization on aGC-efficacy and examined whether peri-operative antibiotic treatment (ABT) improved patient outcome.

Methods

Intratumoral bacteria were detected by immunohistochemistry (IHC) for lipopolysaccharide (gram-negative) and lipoteichoic acid (gram-positive) in the samples of 342 resected PDAC patients treated with either aGC or none / non-gemcitabine-based adjuvant chemotherapy (naGC). Preoperative ABT was defined as ABT for more than 24 hours within 30 days before resection. Postoperative ABT was defined as ABT for more than 24 hours within 30 days after resection. Data of 177 patients from the TCGA database were used for validation.

Results

High bacterial colonization (bac^HI) conferred worse disease-free survival (DFS, 9.4 vs 19.1 months, p<0.001) and overall survival (OS, 19.4 months vs 34.0 months, p<0.001) in aGC patients, but made no statistical difference in naGC patients (p=0.66 and p=0.42). Bac^HI did not correlate with the tumors transcriptional subtype, pre-operative ATB, bile duct interventions or other prognostic clinicopathological variables. Pre-operative ABT did not affect patient outcome, irrespective of adjuvant chemotherapy. Post-operative ABT significantly improved patientś DFS (17.5 vs. 10.8 months, p<0.001) and OS (37.8 vs. 20.6 months, p<0.001) in the aGC cohort, but not in the naGC cohort (p=0.60 and p=0.97). The findings were confirmed by inverse propensity score weighted multivariable Cox regression analyses and in the external validation cohort.

Conclusions

High intratumoral bacterial abundance is a negative predictor of adjuvant gemcitabine efficacy in PDAC but can be overcome by post-operative antibiotic treatment prior adjuvant therapy. Detection of intratumoral bacteria in resection specimens by IHC may guide the use of antibiotics to improve therapy response and patient outcome.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.