Bacterial lipopolysaccharide as negative predictor of gemcitabine efficacy in advanced pancreatic cancer - translational results from the AIO-PK0104 Phase 3 study

Guenther, Michael; Haas, Michael; Heinemann, Volker; Kruger, Stephan; Westphalen, Christoph Benedikt; Bergwelt-Baildon, Michael von; Mayerle, Julia; Werner, Jens; Kirchner, Thomas; Boeck, Stefan und Ormanns, Steffen (2020): Bacterial lipopolysaccharide as negative predictor of gemcitabine efficacy in advanced pancreatic cancer - translational results from the AIO-PK0104 Phase 3 study. In: British Journal of Cancer, Bd. 123, Nr. 9: S. 1370-1376

Abstract

Background: Gram-negative bacteria mediated gemcitabine resistance in pre-clinical models. We determined if intratumoural lipopolysaccharide (LPS) detection by immunohistochemistry is associated with outcome in advanced pancreatic ductal adenocarcinoma (PDAC) treated with gemcitabine and non-gemcitabine containing 1st-line chemotherapy. Methods We examined LPS on tumour tissue from 130 patients treated within the randomised AIO-PK0104 trial and a validation cohort (n = 113) and analysed the association of LPS detection to patient outcome according to treatment subgroups. Results: In 24% of samples from the AIO-PK0104 study LPS was detected;in LPS-positive patients median OS was 4.4 months, compared to 7.3 months with LPS negative tumours (HR 1.732,p = 0.010). A difference in OS was detected in 1st-line gemcitabine-treated patients (n = 71;HR 2.377,p = 0.002), but not in the non-gemcitabine treatment subgroup (n = 59;HR 1.275,p = 0.478). Within the validation cohort, the LPS positivity rate was 23%, and LPS detection was correlated with impaired OS in the gemcitabine subgroup (n = 94;HR 1.993,p = 0.008) whereas no difference in OS was observed in the non-gemcitabine subgroup (n = 19;HR 2.596,p = 0.219). Conclusions: The detection of intratumoural LPS as surrogate marker for gram-negative bacterial colonisation may serve as a negative predictor for gemcitabine efficacy in advanced PDAC.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0007-0920
• Sprache: Englisch