Combined systemic inflammation score (SIS) correlates with prognosis in patients with advanced pancreatic cancer receivi
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ORIGINAL ARTICLE – CLINICAL ONCOLOGY
Combined systemic inflammation score (SIS) correlates with prognosis in patients with advanced pancreatic cancer receiving palliative chemotherapy M. Markus1,2 · A. Abendroth1,3 · R. Noureddine1 · A. Paul4,10,12 · S. Breitenbuecher5 · I. Virchow1,12 · K. W. Schmid6,10,12 · P. Markus7 · B. Schumacher8 · M. Wiesweg1,12 · J. Wendling1,12 · B. Mende9 · J. T. Siveke10,11,12 · M. Schuler1,10,12 · S. Kasper1,10,12 Received: 13 May 2020 / Accepted: 18 August 2020 © The Author(s) 2020
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 1 mg/dl) and low albumin-levels ( 5 mg/dl and 62.5% had an mGPS > 1. First, we correlated the SIR parameters with established negative prognostic markers: grading, metastatic disease (M1) and elevated CA19-9 levels (suppl. Table 1). We found that all SIR markers correlated with at least two known negative prognostic markers. Next, we studied the impact of the SIR markers on treatment outcomes. All evaluated markers significantly correlated with the median OS upon first-line palliative chemotherapy (Table 4; Fig. 2a; suppl. Figs. 2 A, 3 A, 4 A, 5 A). Patients with a LMR > 2.8 had a median OS of 12.8 months compared to patients with a LMR 65 years Age > 70 years Stage at diagnosis Primary location
Histology Grading
Bilirubin > 1.5ULN Initial CA 19–9 (median) Primary resect
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