Bacterial lipopolysaccharide as negative predictor of gemcitabine efficacy in advanced pancreatic cancer – translational results from the AIO-PK0104 Phase 3 study
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-gemcitab...
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Veröffentlicht in: | British journal of cancer 2020-10, Vol.123 (9), p.1370-1376 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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.
Clinical trial registry
The Clinical trial registry identifier is NCT00440167. |
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ISSN: | 0007-0920 1532-1827 |
DOI: | 10.1038/s41416-020-01029-7 |