Preoperative Systemic Immune-Inflammation Index (SII) as a Superior Predictor of Long-Term Survival Outcome in Patients With Stage I-II Gastric Cancer After Radical Surgery

Abstract

Background: Systemic immune-inflammation index (SII), calculated by immunoinflammatory cell counts of peripheral blood, is considered a predictor of survival outcome in several solid tumors, including gastric cancer (GC). However, there is no study focusing on the prognostic value of SII in the early stage of GC. This study aims to compare prognostic prediction capabilities of several inflammatory indices, nutritional indices, and tumor markers to further verify the superior prognostic value of SII in stage I-II GC patients after surgery.

Methods: In this study, 548 patients (358 in the training group and 190 in the validation group) with stage I-II GC after radical surgery were retrospectively analyzed. The peripheral blood indices of interest were SII, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), advanced lung cancer inflammation index (ALI), systemic inflammation score (SIS), prognostic nutritional index (PNI), body mass index (BMI), albumin, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate-associated antigen 19-9 (CA19-9), and alpha-fetoprotein (AFP). The time-dependent receiver operating characteristic (t-ROC) curves and the area under the curve (AUC) were used to determine the optimal cutoff value and prognostic ability of each parameter. Kaplan-Meier curves and multivariable Cox regression models were used to evaluate independent prognostic factors. The nomogram was constructed based on the result of bidirectional stepwise regression model.

Results: The optimal cutoff value of SII was 508.3. The 5-year overall survival rate of the low SII (SII-L) group was significantly higher than that of the high SII (SII-H) group (92% vs. 80%, P < 0.001), especially in the elderly and stage II patients (91% vs. 73%, P = 0.001; 86% vs. 67%, P = 0.003, respectively). The significant prognostic values of SII were consistent in most subgroups. In multivariate analysis, SII and CA19-9 were the only two independent prognostic hematology indices. The AUC value of SII (0.624) was greater than that of CA19-9 (0.528) and other prognostic parameters. Adding SII to the conventional model improved the predictive ability of 5-year overall survival as shown by the significantly increased net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (P = 0.033, P = 0.053, respectively) and modestly improved consistency index (C-index) (increased by 1.6%). External validation of SII-based nomogram demonstrated favorable predictive performance and discrimination. In addition, interactive web dynamic nomogram was published to facilitate clinical use.

Conclusion: SII is a simple but powerful index with a high predictive value to predict survival outcome in patients with stage I-II GC after radical operation. The SII-based nomogram can provide intuitive and accurate prognosis prediction of individual patients.

Keywords: dynamic nomogram; hematological biomarkers; inflammation indices; nutrition indices; prognosis; serum tumor markers; stage I–II gastric cancer.

Figure 1

Flow diagram of the patient selection process.

Figure 2

Subgroup survival analyses for different immunoinflammatory indices: (A) SII. (B) MLR. (C) ALI. Survival curves of OS comparing SII-L group and SII-H group according to the BMI score: (D) In the BMI < 18.5 group. (E) In the 18.5 ≤ BMI < 25.0 group. (F) In the BMI ≥ 25.0 group. SII, systemic immune-inflammation index; MLR, monocyte to lymphocyte ratio; ALI, advanced lung cancer inflammation index; BMI, body mass index.

Figure 3

Survival curves of OS comparing SII-L group and SII-H group based on the age, TNM stage, and adjuvant chemotherapy status. (A) In the non-elderly group. (B) In the elderly group. (C) In the stage I group. (D) In the stage II group. (E) In the non-adjuvant group. (F) In the adjuvant group. SII, systemic immune-inflammation index.

Figure 4

Forest plots for subgroup analyses of SII in stage I–II GC. BMI, body mass index; ECOG, Eastern Cooperative Oncology Group; CEA, carcinoembryonic antigen; CA125, cancer antigen 125; CA19-9, carbohydrate associated antigen 19-9; AFP, alpha-fetoprotein.

Figure 5

Predictive abilities of SII and other hematological indices for OS examined using t-ROC curves. (A) Predictive ability of SII and immunoinflammatory indices. (B) Predictive ability of SII and nutritional indices. (C) Predictive ability of SII and tumor markers. NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; MLR, monocyte to lymphocyte ratio; ALI, advanced lung cancer inflammation index; SII, systemic immune-inflammation index; SIS, systemic inflammation score; PNI, prognostic nutritional index; BMI, body mass index; CEA, carcinoembryonic antigen; CA125, cancer antigen 125; CA19-9, carbohydrate associated antigen 19-9; AFP, alpha-fetoprotein.

Figure 6

Dynamic change for predictive abilities of SII and CA19-9 during the observation period. SII, systemic immune-inflammation index; CA19-9, carbohydrate associated antigen 19-9.

Figure 7

Nomogram for 1–5-year overall survival in stage I–II GC. (A) Conventional nomogram with significant clinical factors. (B) SII-based survival nomogram with SII and significant clinical factors. SII, systemic immune-inflammation index; CA19-9, carbohydrate associated antigen 19-9.

Figure 8

Decision curve analysis of the prediction model in the (A) training group and (B) validation group. SII, systemic immune-inflammation index.

Figure 9

The calibration curve of nomograms for predicting 5-year overall survival. (A) Conventional nomogram and (B) SII-based nomogram in the training group. (C) SII-based nomogram in the validation group. SII, systemic immune-inflammation index.