Systemic Immune-Inflammation Index and Changes of Neutrophil-Lymphocyte Ratio as Prognostic Biomarkers for Patients With Pancreatic Cancer Treated With Immune Checkpoint Blockade

Abstract

The efficacy of current treatment regimens for pancreatic cancer (PC) remains unsatisfactory. In recent years, immune checkpoint blockade (ICB) therapy has shown promising anti-tumor outcomes in many malignancies, including PC. Inexpensive and readily available biomarkers which predict therapeutic responses and prognosis are in critical need. Systemic immune-inflammation index (SII) and neutrophil-lymphocyte ratio (NLR) are emerging predictors for prognosis of various tumors. We aim to investigate the prognostic significance of baseline SII, NLR, and their changes in PC patients treated with ICB. Our retrospective analysis included PC patients treated with ICB therapy in the Chinese PLA General Hospital. All demographic, biological, and clinical data were extracted from medical records. Relative changes of SII after two doses of ICB were defined as ΔSII% and calculated as (SII_{after 2 doses}-SII_baseline)/SII_baseline, and so was the case for ΔNLR%. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan-Meier curves. The prognostic significance of baseline SII, NLR, and their changes was assessed in univariate and multivariate analyses using the Cox proportional hazard regression model. In total, 122 patients with PC treated with ICB were included in the present analysis. Elevated baseline SII (HR=3.28; 95% CI:1.98-5.27; P=0.03) and ΔNLR% (HR=2.21; 95% CI:1.03-4.74; P=0.04) were significantly correlated with an increased risk of death. For PC patients receiving ICB combined with chemotherapies or radiotherapies as the first-line treatment, increased baseline SII was a negative predictor for both OS (HR=8.06; 95% CI:1.71-37.86; P=0.01) and PFS (HR=2.84; 95%CI:1.37-10.38; P=0.04). Our study reveals the prognostic value of baseline SII and NLR changes in PC patients receiving ICB therapy. The clinical utility of these prognostic biomarkers needs to be further studied in prospective studies.

Keywords: immune checkpoint blockade; immunotherapy; neutrophil-lymphocyte ratio; pancreatic cancer; prognosis; systemic immune-inflammation index.

Figure 1

Kaplan-Meier curves for overall survival (OS) of pancreatic cancer (PC) patients treated with immune checkpoint blockade (ICB) therapy. (A) Association between baseline systemic immune-inflammation index (SII) and OS. (B) Association between neutrophil-lymphocyte ratio (NLR) changes and OS.

Figure 2

Kaplan-Meier curves for progression-free survival (PFS) of pancreatic cancer (PC) patients receiving immune checkpoint blockade (ICB) therapy. (A) Association between neutrophil-lymphocyte ratio (NLR) changes and progression-free survival (PFS). (B) Association between baseline absolute neutrophil count (ANC) and PFS. (C) Association between baseline hemoglobin (HGB) and PFS.

Figure 3

Kaplan-Meier curves for survival of pancreatic cancer (PC) patients receiving immune checkpoint blockade (ICB) combined with chemotherapies as the first-line treatment. (A) Association between baseline systemic immune-inflammation index (SII) and overall survival (OS). (B) Association between baseline SII and progression-free survival (PFS).