Klara Dorman1,2, Miriam Gerckens1,3, Stefan Boeck4,5, Stefan Holdenrieder3,6, Stephan Kruger1, Kimberly Krueger3, Zsuzsanna Mayer3, Alexander Rupp3, Danmei Zhang1,2, Lena Weiss1, C Benedikt Westphalen1, Michael Haas1, Michael Guenther7, Steffen Ormanns7, Frank Klawonn3,8,9, Jens Werner10, Michael von Bergwelt-Baildon1,2, Volker Heinemann1,2. 1. Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany. 2. German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany. 3. Munich Biomarker Research Center, Institute of Laboratory Medicine, German Heart Center, Technical University of Munich, Munich, Germany. 4. Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany. stefan.boeck@med.uni-muenchen.de. 5. German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany. stefan.boeck@med.uni-muenchen.de. 6. Center for the Evaluation of Biomarkers, CEBIO, Munich, Germany. 7. Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany. 8. Department of Computer Science, Ostfalia University, Wolfenbüttel, Germany. 9. Biostatistics Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany. 10. Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany.
Abstract
PURPOSE: Novel biomarkers to better predict outcome and select the best therapeutic strategy for the individual patient are necessary for pancreatic ductal adenocarcinoma (PDAC). METHODS: Using a panel assay, multiple biomarkers (IFN-γ, IL-10, IL-6, IL-8, TNF-α, CEA, CA 19-9, CYFRA 21-1, HE4, PD-1 and PD-L1 levels) were measured in serum samples of 162 patients with resected, locally advanced and metastatic PDAC in this retrospective single-center study. Optimal cut-off values to differentiate prognostic subgroups with significantly different overall survival (OS) were determined by receiver operator characteristics and Youden Index analysis. Marker levels were assessed before the start of chemotherapy and correlated with OS by univariate and multivariate Cox analysis. RESULTS: Median OS for resected patients was 28.2 months, for locally advanced patients 17.9 months and for patients with metastatic disease 8.6 months. CYFRA 21-1 and IL-8 discriminated metastatic from locally advanced patients best (AUC 0.85 and AUC 0.81, respectively). In univariate analyses, multiple markers showed prognostic relevance in the various subgroups. However, multivariate Cox models comprised only CYFRA 21-1 in the resected group (HR 1.37, p = 0.015), IL-10 in locally advanced PDAC (HR 10.01, p = 0.014), as well as CYFRA 21-1 and CA 19-9 in metastatic PDAC (p = 0.008 and p = 0.010) as an independent prognostic marker for overall survival. CONCLUSION: IL-10 levels may have independent prognostic value in locally advanced PDAC, whereas CYFRA 21-1 levels are prognostic after PDAC surgery. CYFRA 21-1 and IL-8 have been identified to best discriminate metastatic from locally advanced patients.
PURPOSE: Novel biomarkers to better predict outcome and select the best therapeutic strategy for the individual patient are necessary for pancreatic ductal adenocarcinoma (PDAC). METHODS: Using a panel assay, multiple biomarkers (IFN-γ, IL-10, IL-6, IL-8, TNF-α, CEA, CA 19-9, CYFRA 21-1, HE4, PD-1 and PD-L1 levels) were measured in serum samples of 162 patients with resected, locally advanced and metastatic PDAC in this retrospective single-center study. Optimal cut-off values to differentiate prognostic subgroups with significantly different overall survival (OS) were determined by receiver operator characteristics and Youden Index analysis. Marker levels were assessed before the start of chemotherapy and correlated with OS by univariate and multivariate Cox analysis. RESULTS: Median OS for resected patients was 28.2 months, for locally advanced patients 17.9 months and for patients with metastatic disease 8.6 months. CYFRA 21-1 and IL-8 discriminated metastatic from locally advanced patients best (AUC 0.85 and AUC 0.81, respectively). In univariate analyses, multiple markers showed prognostic relevance in the various subgroups. However, multivariate Cox models comprised only CYFRA 21-1 in the resected group (HR 1.37, p = 0.015), IL-10 in locally advanced PDAC (HR 10.01, p = 0.014), as well as CYFRA 21-1 and CA 19-9 in metastatic PDAC (p = 0.008 and p = 0.010) as an independent prognostic marker for overall survival. CONCLUSION: IL-10 levels may have independent prognostic value in locally advanced PDAC, whereas CYFRA 21-1 levels are prognostic after PDAC surgery. CYFRA 21-1 and IL-8 have been identified to best discriminate metastatic from locally advanced patients.
Authors: Stefan Boeck; Michael Haas; Rüdiger P Laubender; Frank Kullmann; Christina Klose; Christiane J Bruns; Ralf Wilkowski; Petra Stieber; Stefan Holdenrieder; Hannes Buchner; Ulrich Mansmann; Volker Heinemann Journal: Clin Cancer Res Date: 2010-01-26 Impact factor: 12.531
Authors: Thierry Conroy; Françoise Desseigne; Marc Ychou; Olivier Bouché; Rosine Guimbaud; Yves Bécouarn; Antoine Adenis; Jean-Luc Raoul; Sophie Gourgou-Bourgade; Christelle de la Fouchardière; Jaafar Bennouna; Jean-Baptiste Bachet; Faiza Khemissa-Akouz; Denis Péré-Vergé; Catherine Delbaldo; Eric Assenat; Bruno Chauffert; Pierre Michel; Christine Montoto-Grillot; Michel Ducreux Journal: N Engl J Med Date: 2011-05-12 Impact factor: 91.245
Authors: Rachel F Gabitass; Nicola E Annels; Deborah D Stocken; Hardev A Pandha; Gary W Middleton Journal: Cancer Immunol Immunother Date: 2011-06-05 Impact factor: 6.968
Authors: S Boeck; C Wittwer; V Heinemann; M Haas; C Kern; P Stieber; D Nagel; S Holdenrieder Journal: Br J Cancer Date: 2013-04-11 Impact factor: 7.640
Authors: E G Chiorean; D D Von Hoff; M Reni; F P Arena; J R Infante; V G Bathini; T E Wood; P N Mainwaring; R T Muldoon; P R Clingan; V Kunzmann; R K Ramanathan; J Tabernero; D Goldstein; D McGovern; B Lu; A Ko Journal: Ann Oncol Date: 2016-01-22 Impact factor: 32.976