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Circulating biomarkers and outcomes from a randomised phase 2 trial of gemcitabine versus capecitabine-based chemoradiotherapy for pancreatic cancer

Willenbrock, Frances, Cox, Catrin M., Parkes, Eileen E., Wilhelm-Benartzi, Charlotte S., Abraham, Aswin G., Owens, Robert, Sabbagh, Ahmad, Jones, Christopher M., Hughes, Daniel L. I., Maughan, Tim, Hurt, Christopher N., O'Neill, Eric E. and Mukherjee, Somnath 2020. Circulating biomarkers and outcomes from a randomised phase 2 trial of gemcitabine versus capecitabine-based chemoradiotherapy for pancreatic cancer. British Journal of Cancer 10.1038/s41416-020-01120-z

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Abstract

Background The Phase 2 SCALOP trial compared gemcitabine with capecitabine-based consolidation chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC). Methods Thirty-five systematically identified circulating biomarkers were analysed in plasma samples from 60 patients enroled in SCALOP. Each was measured in triplicate at baseline (prior to three cycles of gemcitabine-capecitabine induction chemotherapy) and, for a subset, prior to CRT. Association with overall survival (OS) was determined using univariable Cox regression and optimal thresholds delineating low to high values identified using time-dependent ROC curves. Independence from known prognostic factors was assessed using Spearman correlation and the Wilcoxon rank sum test prior to multivariable Cox regression modelling including independent biomarkers and known prognostic factors. Results Baseline circulating levels of C-C motif chemokine ligand 5 (CCL5) were significantly associated with OS, independent of other clinicopathological characteristics. Patients with low circulating CCL5 (CCL5low) had a median OS of 18.5 (95% CI 11.76–21.32) months compared to 11.3 (95% CI 9.86–15.51) months in CCL5high; hazard ratio 1.95 (95% CI 1.04–8.65; p = 0.037). Conclusions CCL5 is an independent prognostic biomarker in LAPC. Given the known role of CCL5 in tumour invasion, metastasis and the induction of an immunosuppressive micro-environment, targeting of CCL5-mediated pathways may offer therapeutic potential in pancreatic cancer.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Medicine
Centre for Trials Research (CNTRR)
Publisher: Springer Nature
ISSN: 0007-0920
Funders: CRUK
Date of Acceptance: 2 October 2020
Last Modified: 27 Oct 2020 13:30
URI: http://orca.cf.ac.uk/id/eprint/135928

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