Prognostic role of inflammatory biomarkers in patients with advanced pancreatic adenocarcinoma undergoing first-line chemotherapy

The aim of the current study was to examine the prognostic significance of inflammatory biomarkers in patients with locally advanced or metastatic pancreatic adenocarcinoma undergoing first-line chemotherapy with nab-paclitaxel and gemcitabine. In the current cohort study data from 57 patients were retrospectively collected. All patients had histologically or cytologically confirmed pancreatic locally advanced or metastatic adenocarcinoma and were treated with first-line nab-paclitaxel and gemcitabine from July 2014 to February 2020. White cell (WBC), neutrophil (NEUT), lymphocyte (LYMPH), monocyte (MONO) and platelet (PLT) blood levels during the last two days before the start of the first cycle of chemotherapy were measured. Median neutrophil to lymphocyte ratio (NLR), median monocyte to lymphocyte ratio (MLR), median systemic inflammatory response index (SIRI=NEUT × MONO/LYMPH) and median platelet-to-lymphocyte ratio PLR were calculated. Median age was 67 years (range, 43-81), while 29 (50.9%) male and 28 (49.1%) female patients were included in the study. PS (ECOG) was zero in 32 (56.2%) patients, one in 21 (36.8%) and two in 4 (7.0%) patients. Forty seven (82.5%) patients had stage IV and 10 (17.5%) had stage III disease. After a median follow-up of 20.6 months (range, 1.1-37.3), 48 (84.2%) developed progressive disease and 41 (71.9%) died of disease. Median progression-free survival (PFS) was 5.1 months (95%CI, 3.6-6.6) and median overall survival (OS) was 9.9 months (95%CI, 6.2-13.6). Patients with stage III had median PFS 9.2 months (95%CI 3.0-15.4), while stage IV patients had median PFS 5.1 months (95%CI 3.3-6.9), with statistically significant difference (p=0.011). Increasing NLR levels were correlated with poorer PFS (HR 1.10, 95%CI 1.01-1.20,p=0.033) but not with OS (HR 1.07,95%CI 0.98-1.18,p=0.139). Cox proportional hazard models confirmed that higher NLR levels were independently associated with poorer PFS (HR 1.14, 95%CI 1.03-1.25, p=0.009) and poorer OS (HR 1.11, 95%CI 1.01-1.23,p=0.037). Also, PS ECOG 1-2 (compared to PS 0) showed independent prognostic significance for PFS (HR 2.51, 95%CI 1.34-4.69,p=0.004) and OS (HR 3.00, 95%CI 1.53-5.76, p=0.001). In contrast, tumor stage did not demonstrate independent prognostic significance. Exploratory analysis examined the prognostic significance of different NLR cutoffs (by increasing the NLR value by 0.5) for PFS and OS. The best cutoff was NLR ≥4 vs. < 0.001) and longest median OS compared to the group with PS ECOG 1-2 and NLR ≥4 (14.0 vs. 8.2 vs. 5.7, respectively, p< 0.001). The present retrospective analysis revealed clinically meaningful subgroups with distinct prognoses according to inflammatory biomarkers and performance status, irrespective of tumor stage, in patients with advanced pancreatic adenocarcinoma treated with first-line nab-paclitaxel – gemcitabine.