Abstract
PurposeThe 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.MethodsA 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.ResultsAll 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).ConclusionRoutinely assessed SIR biomarkers have potential to support therapeutic decision making in patients with metastatic PDAC.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) has a rising incidence over the last decades and is the fourth leading cause of cancer-related death in Western countries (Saif 2013)
These systemic inflammatory response (SIR) parameters such as the C-reactive protein (CRP) or different levels of white blood cells and their respective ratios such as the neutrophil–lymphocyte (NLR) ratio and others has been previously correlated with the risk of recurrence and overall survival in curatively or palliatively treated malignancies including PDAC (Hang et al 2017; Martin et al 2014; Proctor et al 2011; Schlick et al 2019; Stotz et al 2013, 2015)
859 patients with PDAC diagnosed between January 2005 and August 2011 were identified in the database of our hospital
Summary
Pancreatic ductal adenocarcinoma (PDAC) has a rising incidence over the last decades and is the fourth leading cause of cancer-related death in Western countries (Saif 2013). Intratumoral inflammation is one essential hallmark of cancer initiation and progression through DNA damage and activation of intracellular signaling pathways (Hanahan and Weinberg 2011) This is supported by the fact that chronic pancreatitis is one of the major risk factors for the development of PDAC. The activation of the systemic immune system by the local intra-tumoral inflammation can be measured by blood-based parameters These systemic inflammatory response (SIR) parameters such as the C-reactive protein (CRP) or different levels of white blood cells and their respective ratios such as the neutrophil–lymphocyte (NLR) ratio and others has been previously correlated with the risk of recurrence and overall survival in curatively or palliatively treated malignancies including PDAC (Hang et al 2017; Martin et al 2014; Proctor et al 2011; Schlick et al 2019; Stotz et al 2013, 2015). Most studies focused only on one SIR marker and did not use a combination of different markers for a better dissection of patients’ prognosis
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