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 (SIIafter 2 doses-SIIbaseline)/SIIbaseline, 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.

Prognostic and clinicopathological significance of systemic immune-inflammation index in pancreatic cancer: a meta-analysis of 2,365 patients

“…The basic characteristics of the included studies are listed in Supplementary Table 1 ; these studies were published from 2019 to 2021. The 11 cohort studies were conducted in China (n=4) [ 12 , 14 , 15 , 17 , 18 ], the Netherlands (n=2) [ 10 ], Austria (n=1) [ 11 ], Italy (n=1) [ 16 ], and the United States of America (USA) (n=1) [ 13 ]. The sample size ranged from 27 to 420, and the total sample size was 2,365.…”

“…The sample size ranged from 27 to 420, and the total sample size was 2,365. Nine cohort studies [ 10 – 14 , 16 , 17 ] were published in English and two [ 15 , 18 ] were published in Chinese. Regarding the study design, nine cohorts [ 10 , 12 – 18 ] were retrospective studies and two [ 11 , 12 ] were prospective studies.…”

“…The cut-off value of SII ranged from 440 to 1200. Nine cohorts [ 11 – 18 ] reported the prognostic role of SII in OS, six cohorts [ 10 – 12 , 16 , 17 ] reported an association between SII and RFS/PFS/DFS, and two cohorts reported CSS [ 10 ]. The Newcastle-Ottawa Scale (NOS) scores ranged from 6 to 8, indicating that all the studies included were of high quality.…”

“…Six cohorts, with 1,297 subjects [ 10 – 12 , 16 , 17 ], reported the prognostic value of SII for RFS/PFS/DFS. As shown in Figure 3 and Table 1 , the pooled results were as follows: HR=1.52, 95% CI=1.01–2.28, p=0.045.…”

The Predictive Value of Systemic Immune-Inflammation Index on Bladder Recurrence on Upper Tract Urothelial Carcinoma Outcomes after Radical Nephroureterectomy

“…There have been studies reporting SII significance in the survival of patients undergoing immunotherapy [26]. Aside from the baseline biomarkers, we believe that the alteration of biomarkers during immunotherapy treatment would provide greater information and indicate an immediate effect from the immunotherapy treatment itself [27]. Shang et al [27] reported that the changes of NLR as prognostic biomarkers for patients with pancreatic cancer treated with immunotherapy in multivariate analysis.…”