Host systemic inflammatory response influences outcome in pancreatic cancer

Abstract

This review of the influence of host systemic inflammatory response(SIR) on the outcome of pancreatic ductal adenocarcinoma (PDAC)was the kernel of the 2014 George E Palade Memorial Prize Lecture at the Combined IAP-EPC Meeting held June 25-8 in Southampton,UK. The ability of the modified Glasgow Prognostic Score(mGPS) to stratify cancer outcomes has been demonstrated in >50 studies including >25000 patients from many countries. Other markers of SIR such as Prognostic Index and neutrophil/lymphocyte ratio(NLR) may also be used emphasising the non homogeneity of the PDAC patients. The mGPS score 0 is associated with better outcome,while scores of 1 & 2 are linked to poor performance status, greater weight loss, comorbidity and earlier death. Two papers show in resectable PDAC that longer life (27-37 months) occurs with mGPS 0, and < 18 months for mGPS 1 and 2, such that alternative therapy employing RFA may well be better than resection in those patients. In the greater number of PDAC patients unsuitable for resection the JAK-STAT inhibitor, ruxolitinib, has been found only to favourably modify PDAC in those with mGPS 1 or 2. Likewise the possible benefits of older anti inflammatory agents may be confined to these patients. An urgent reappraisal of the prognostic and therapeutic implications is now required in PDAC. Local inflammatory responses(LIR) are beneficial in PDAC and other cancers. Four grade stratification systems using Klintrup histology, T cell subtype analysis and Galon immune scores are accurate prognosticators.

Keywords: Anti-inflammatory drugs; Non-homogeneity of cancer patients; RFA with chemo-radiotherapy; Radical surgical resection; Systemic and local inflammatory responses; mGPS and PDAC outcomes.