267 Background: Interleukin-6 (IL-6) and YKL-40 (CHI3L1) are produced by pancreatic cancer (PC) cells and macrophages and activate inflammation. The aim of this prospective-retrospective biomarker study was to determine the prognostic value of serum IL-6 and YKL-40 and systemic inflammatory response in patients with PC receiving palliative chemotherapy. Methods: 625 patients with PC (M/F: 283/342; age <70 vs. ≥70: 395/230; ECOG PS of 0/1/2/3: 214/315/92/4; stage 3 vs. 4: 129/496; treated with gemcitabine n=437, FOLFIRINOX n=117, gemcitabine and nab-Paclitaxel n=54 or other n=17) were included in the BIOPAC biomarker study from 5 hospitals in Denmark. Pretreatment serum values of IL-6 (R&D Systems), YKL-40 (Quidel), and CA 19-9 (Siemens) were determined. Patients were grouped as low vs. high, dichotomized using cut-off for IL-6 > 4.92 pg/ml, for CA19-9 > 2183 U/ml and for YKL-40 > 95% age-corrected percentile. The main outcome was overall survival (OS) and hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were computed using Cox proportional hazards regression. Results: 598 (95.7%) patients died during follow-up. In univariate analysis elevated IL-6 (HR 1.93, 95% CI 1.63-2.28) and elevated YKL-40 (HR 1.74, 95% CI 1.47-2.05) were associated with short OS. Similar results were found if IL-6 and YKL-40 were included as continuous log2-transformed variables. Multivariable analysis showed that elevated IL-6 (HR 1.61, 95% CI 1.33-1.94), elevated YKL-40 (HR 1.36, 95% CI 1.13-1.64), elevated CA19-9 (HR 1.30, 95% CI 1.09-1.56), higher PS (1 vs. 0; HR 1.46, 95% CI 1.21-1.77 and PS 2 vs. 0; HR 2.73, 95% CI 2.08-3.58) and stage 4 vs. 3 (HR 1.79, 95% CI 1.44-2.24) were independently associated with a poor OS. In a subgroup of 386 patients with available laboratory data, higher C-reactive protein (HR 1.20, 95% CI 1.13-1.26), white blood cells (HR 1.41, 1.17-1.71) and absolute neutrophils count (HR 1.35, 95% CI 1.15-1.59) log2-transformed and adjusted for age, sex, PS, CA 19-9 and stage were associated with short OS. Conclusions: Serum IL-6, YKL-40 and CA19-9 along with CRP, WBC and ANC are independent prognostic biomarkers in patients with unresectable PC.
Serum lactate dehydrogenase predicts prognosis and correlates with systemic inflammatory response in patients with advanced pancreatic cancer after gemcitabine-based chemotherapy
