Combined systemic inflammation score (SIS) correlates with prognosis in patients with advanced pancreatic cancer receiving palliative chemotherapy.

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.

Long-term outcome of patients with advanced pancreatic cancer treated with sequential chemotherapies before the era of modern combination therapy protocols.

INTRODUCTION: Patients (pts) with locally advanced (LAPC) or metastatic pancreatic ductal adenocarcinoma (mPDAC) have a dismal prognosis. Recently, new combination chemotherapies such as FOLFIRINOX and nab-paclitaxel/gemcitabine have demonstrated superiority over gemcitabine monotherapy. However, a substantial proportion of pts cannot tolerate these intensive front-line protocols. Moreover, the long-term superiority of multiagent protocols over less intensive strategies remains to be shown. To provide a benchmark for future studies, we analyzed the outcome of patients with LAPC or mPDAC treated at the West German Cancer Center before the FOLFIRINOX/nab-paclitaxel + gemcitabine era. METHODS: This retrospective analysis included 201 consecutive pts with LAPC and mPDAC treated between 2007 and 2011. Efficacy parameters were correlated with type of chemotherapy, number of treatment lines and clinicopathological parameters. RESULTS: Gemcitabine monotherapy was given as first-line therapy in 51.1%, whereas 48.9% received combination chemotherapies such as gemcitabine/oxaliplatin or FOLFOX. Patients received a median of two lines of treatment, with 54.8% receiving second-line and 37.9% receiving third- and further-line therapies. There was no significant difference between gemcitabine monotherapy and combination therapies. Despite moderate activity of first-line treatment, median overall survival for LAPC was 11.3 months and 8.7 months for mPDAC. Multivariate analysis identified age and number of treatment lines as prognostic markers. CONCLUSION: The long-term outcome of unselected pts with LAPC and mPDAC treated before the introduction of aggressive multiagent chemotherapy protocols compares favorably with the results of contemporary benchmark trials. This suggests a multifactorial benefit from interdisciplinary care provided over sequential treatment lines at high volume expert centers.