M Markus1,2, A Abendroth1,3, R Noureddine1, A Paul4,5,6, S Breitenbuecher7, I Virchow1,6, K W Schmid8,5,6, P Markus9, B Schumacher10, M Wiesweg1,6, J Wendling1,6, B Mende11, J T Siveke5,12,6, M Schuler1,5,6, S Kasper13,14,15. 1. West German Cancer Center, Department of Medical Oncology, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany. 2. Department of Anesthesiology and Operative Intensive Care Medicine (CCMCVK), Charité - University Hospital Berlin, Berlin, Germany. 3. Department of Hematology, Oncology, and Clinical Immunology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 4. West German Cancer Center, Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany. 5. German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany. 6. Medical Faculty, University Duisburg-Essen, Essen, Germany. 7. Institute for Quality Assurance, University Hospital Essen, Essen, Germany. 8. West German Cancer Center, Institute of Pathology Essen, University Hospital Essen, Essen, Germany. 9. Department of General Surgery and Traumatology, Elisabeth Hospital Essen, Essen, Germany. 10. Department of Gastroenterology, Elisabeth Hospital Essen, Essen, Germany. 11. Central Pharmacy, University Hospital Essen, Essen, Germany. 12. West German Cancer Center, Institute for Developmental Cancer Therapeutics, University Hospital Essen, Essen, Germany. 13. West German Cancer Center, Department of Medical Oncology, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany. stefan.kasper-virchow@uk-essen.de. 14. German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany. stefan.kasper-virchow@uk-essen.de. 15. Medical Faculty, University Duisburg-Essen, Essen, Germany. stefan.kasper-virchow@uk-essen.de.
Abstract
PURPOSE: The prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains dismal. New cytotoxic agents such as nab-paclitaxel and liposomal irinotecan (nal-Iri) have extended the armamentarium of therapeutic options in the last years. Nowadays, sequential therapeutic strategies with moderately toxic chemotherapeutic protocols can be administered to the patients. However, prognostic and predictive biomarkers are still missing to identify those patients, which profit most from a "continuum of care" concept rather than receiving intensive first-line protocols such as FOLFIRINOX. To this end, we retrospectively evaluated the impact of the systemic inflammation as one essential hallmark of cancer in patients with advanced PDAC treated with sequential systemic. METHODS: A cohort of 193 PDAC patients treated at our center from January 2005 to August 2011 were retrospectively evaluated for the following systemic inflammatory response (SIR) markers: neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) C-reactive protein (CRP), and the modified Glasgow Prognostic Score (mGPS). SIR markers were correlated with clinico-pathological findings, response to chemotherapy and overall survival (OS) using Kaplan-Meier curves and Cox proportional models. RESULTS: All evaluated SIR markers were significantly associated with OS in patients with metastatic disease but not in patients with locally advanced PDAC. Interestingly, all SIR markers were only prognostic in patients not receiving antibiotics as surrogate marker for systemic bacterial infections. Based on the evaluated SIR markers, we propose a new Systemic Inflammation Score (SIS), which significantly correlated with reduced OS (HR: 3.418 (1.802-6.488, p < 0.001)) and the likelihood of receiving further-line systemic therapies (p = 0.028). CONCLUSION: Routinely assessed SIR biomarkers have potential to support therapeutic decision making in patients with metastatic PDAC.
PURPOSE: The prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains dismal. New cytotoxic agents such as nab-paclitaxel and liposomal irinotecan (nal-Iri) have extended the armamentarium of therapeutic options in the last years. Nowadays, sequential therapeutic strategies with moderately toxic chemotherapeutic protocols can be administered to the patients. However, prognostic and predictive biomarkers are still missing to identify those patients, which profit most from a "continuum of care" concept rather than receiving intensive first-line protocols such as FOLFIRINOX. To this end, we retrospectively evaluated the impact of the systemic inflammation as one essential hallmark of cancer in patients with advanced PDAC treated with sequential systemic. METHODS: A cohort of 193 PDACpatients treated at our center from January 2005 to August 2011 were retrospectively evaluated for the following systemic inflammatory response (SIR) markers: neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) C-reactive protein (CRP), and the modified Glasgow Prognostic Score (mGPS). SIR markers were correlated with clinico-pathological findings, response to chemotherapy and overall survival (OS) using Kaplan-Meier curves and Cox proportional models. RESULTS: All evaluated SIR markers were significantly associated with OS in patients with metastatic disease but not in patients with locally advanced PDAC. Interestingly, all SIR markers were only prognostic in patients not receiving antibiotics as surrogate marker for systemic bacterial infections. Based on the evaluated SIR markers, we propose a new Systemic Inflammation Score (SIS), which significantly correlated with reduced OS (HR: 3.418 (1.802-6.488, p < 0.001)) and the likelihood of receiving further-line systemic therapies (p = 0.028). CONCLUSION: Routinely assessed SIR biomarkers have potential to support therapeutic decision making in patients with metastatic PDAC.
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