Inflammatory Biomarker Score Identifies Patients with Six-Fold Increased Risk of One-Year Mortality after Pancreatic Cancer

SIMPLE SUMMARY: For 20 years, the CA 19-9 blood test has been the only broadly used biomarker of pancreatic ductal adenocarcinoma (PDAC). We lack easily available biomarkers to help differentiate patients between good, intermediate and poor survivors at the time of PDAC diagnosis. Using one of the largest studies of patients with PDAC, we found that a simple combination of blood tests, namely CRP, CA 19-9 and IL-6, into a single biomarker score was a better marker of one-year survival than the currently recommended CA 19-9 alone or any other combination of the four inflammatory biomarkers examined (CRP, CA 19-9, IL-6 and YKL-40). However, since this is the first study examining this inflammatory biomarker score, future validation studies are needed. Moreover, CRP outperformed CA 19-9 in the majority of patients, thus questioning the routine use of CA 19-9 in patients with PDAC. ABSTRACT: We examined whether elevated plasma C-reactive protein (CRP), carbohydrate antigen (CA) 19-9, interleukin-6 (IL-6) and YKL-40, individually or combined, can identify poor survivors among patients with pancreatic ductal adenocarcinoma (PDAC). We measured CRP, CA 19-9, IL-6 and YKL-40 in 993 patients at the time of PDAC diagnosis. The biomarker score was the sum of biomarker categories, coded 0, 1 and 2 for low, intermediate and high plasma concentrations, respectively. High vs. low levels of CRP, CA 19-9 and IL-6 were each independently associated with a two-fold increased risk of one-year mortality. CRP performed best in patients with advanced and CA 19-9 in patients with low cancer stages. YKL-40 was not associated with mortality and, therefore, was not included in the biomarker score. Compared to the biomarker score = 0, the multifactorially adjusted hazard ratios for one-year mortality were 1.56 (95% confidence interval: 0.99–2.44) for score = 1, 2.22 (1.41–3.49) for score = 2, 3.44 (2.20–5.38) for score = 3, 5.13 (3.21–8.17) for score = 4 and 6.32 (3.84–10.41) for score = 5–6 (p-value for trend = 3 × 10(−31)). This score performed better than any single biomarker or combination of biomarkers when examined in similarly sized or other categories. In conclusion, a combination score of elevated CRP, CA 19-9 and IL-6 identified patients with six-fold higher one-year mortality.