1510P - Exploration of circulating free bacterial DNA as a biomarker for therapy response in metastatic and locally advanced pancreatic cancer patients treated with systemic chemotherapy

Background

Monitoring the efficacy of systemic chemotherapy in pancreatic cancer (PC) is challenging as imaging procedures have limited sensitivity and not all patients secrete CA19-9. Systemic therapies influence the microbiome, but little is known whether its changes affect therapy response. To date, there are no standardized and easily accessible measurement methods established to monitor its changes. In this study, we assessed the effect of changes in the level of circulating free bacterial DNA (cfbDNA) on the outcome of metastatic or locally advanced PC patients treated with systemic chemotherapy.

Methods

The levels of cfbDNA were measured by digital droplet PCR (ddPCR) before initiation of systemic treatment and after 30 days of mFOLFIRINOX (FFX) treatment in the serum of 13 Patients with advanced PC and the changes in cfbDNA levels were compared to patient outcome. None of the patients received anti-infective medication during the chemotherapy administration. The results were validated in the serum samples of 47 patients with locally advanced PC treated within the NEOLAP-AIO-PAK-0113 trial (NCT02125136).

Results

Reduction of cfbDNA levels after 30 days of FFX conferred significantly better progression-free survival (2.9 vs. 14.3 months, p<0.001) and overall survival (8.4 vs. 23.2 months, p=0.006) in patients treated for metastatic PC. These changes did not correlate with disease stage, CA19-9 baseline levels, CA19-9 changes, ECOG, sex or other clinicopathological variables. CfbDNA changes were not associated with immune cell populations as measured by flow cytometry. The predictive character of the changes in cfbDNA levels was confirmed by multivariate cox regression analyses and reproduced in the validation study cohort.

Conclusions

Measurement of cfbDNA provides a tool to monitor changes of the microbiome during systemic therapy and may predict therapy efficacy earlier than other serum biomarkers or imaging approaches to inform therapy decisions. Measuring cfbDNA levels may control the effect of probiotic or antimicrobial therapy in PC patients undergoing systemic therapy to explore the significance of microbiome based therapy strategies in PC.

Clinical trial identification

NCT02125136.

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.