Serum interleukin-6 as a prognostic biomarker for survival in patients with unresectable pancreatic cancer

Background

Patients with pancreatic cancer (PC) have the highest mortality rate of all major cancers. Interleukin-6 (IL-6) is produced by PC cells and macrophages, regulates inflammation and plays an important role in cachexia. The aim of this biomarker study was to determine the clinical utility of serum IL-6 as a prognostic factor. We further explored age, sex, CA 19.9, PS, stage and chemotherapy type as predictors of outcome in patients receiving palliative chemotherapy.

Methods

452 patients with unresectable PC (M/F: 242/210; median age 67.5 (IQR 61.8, 73.0); ECOG Performance Status (PS) of 0/1/2: 150/247/55; locally advanced disease/metastatic: 97/355; treated with gemcitabine n = 337, FOLFIRINOX n= 83, gemcitabine and nab-Paclitaxel n = 14 or capecitabine-containing regimens n = 18) were included in the BIOPAC study from five hospitals in Denmark (2008-2016). Pretreatment and longitudinal serum CA 19.9 (Siemens) and IL-6 were determined (ELISA, R&D Systems).

Results

Patients were grouped into quartiles according to baseline IL-6 values (0.8 to 3.2, 3.2 to 6.4, 6.4 to 14, and ≥14 pg/ml) and CA 19.9 values (1 to 119, 119 to 992, 992 to 7280, and 7280 to 687.000 U/ml. On univariate analysis, IL-6 ≥6.4 pg/ml, CA 19.9, PS, stage, chemotherapy type were identified as significant risk factors for overall survival (OS). Hazard ratio (HR) in quartiles with lowest quartile as reference were 1.20 (95% confidence interval (CI), 0.91–1.57; P = 0.19), 1.87 (95% CI, 1.43–2.46; P 

Conclusions

The serum level of IL-6 is a strong independent prognostic biomarker in patients with unresectable PC that could be used to identify patients with poor outcome. Changes in IL-6 from baseline are predictive for survival.

Clinical trial identification

Ethics committee (nr. KA-20060113). Danish Data Protection Agency (j.nr. 2012-58-0004; HGH-2015-027; I-Suite nr:03960)

Legal entity responsible for the study

Inna Chen

Funding

Herlev Hospital

Disclosure

All authors have declared no conflicts of interest.