The Impacts of Systemic Immune-Inflammation Index on Clinical Outcomes in Gallbladder Carcinoma

Abstract

Background: Systemic immune-inflammation index (SII) is considered to be a prognostic marker in several cancers. However, the prognostic value of baseline pre-operative SII in gallbladder carcinoma (GBC) has not been evaluated. This study aimed to determine the prognostic significance of SII and generate a predictive nomogram. Methods: We retrospectively studied 142 GBC patients who underwent surgical resection at the Peking Union Medical College Hospital between 2003 and 2017. SII, neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR) were evaluated for their prognostic values. A multivariate Cox proportional hazards model was used for the recognition of significant factors. Then, the cohort was randomly divided into the training and the validation set. A nomogram was constructed using SII and other selected indicators in the training set. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram's clinical utility in both the training and the validation set. Results: The predictive accuracy of SII (Harrell's concordance index [C-index]: 0.624), NLR (C-index: 0.626), and LMR (C-index: 0.622) was evaluated. The multivariate Cox model showed that SII was a superior independent predictor than NLR and LMR. SII level (≥600) (hazard ratio [HR]: 1.694, 95% confidence interval [CI]: 1.069-2.684, p = 0.024), carbohydrate antigen (CA) 19-9 level (≥37 U/ml) (HR: 2.407, 95% CI: 1.472-3.933, p < 0.001), and TNM stage (p = 0.026) were selected to construct a nomogram for predicting overall survival (OS). The predictive ability of this model was assessed by C-index (0.755 in the training set, 0.754 in the validation set). Good performance was demonstrated by the calibration plot. A high net benefit was proven by decision curve analysis (DCA). Conclusion: SII is an independent prognostic indicator in GBC patients after surgical resection, and the nomogram based on it is a useful tool for predicting OS.

Keywords: gallbladder carcinoma; nomogram; prognosis; systematic inflammation markers; systemic immune-inflammation index.

Figure 1

Estimated overall survival with (A) systemic immune-inflammation index (SII) >600 (median OS, 11 vs. 34 months, p < 0.001); (B) neutrophil-to-lymphocyte ratio (NLR) > 2.5 (median OS, 12 vs. 37 months, p < 0.001); (C) lymphocyte-to-monocyte ratio (LMR) > 4.7 (median OS, 40 vs. 13 months, p < 0.001).

Figure 2

Receiver operating characteristic analyses for SII (red), NLR (blue), and LMR (green) at 12 (A), 36 (B), and 60 months (C).

Figure 3

(A) The nomogram for predicting 1-, 3-, and 5-year survival probabilities of GBC patients based on SII levels, CA 19-9 levels, and AJCC stage; calibration curves of the nomogram for predicting survival probabilities of 1 (B), 3 (C), and 5 years (D) in the training cohort and 1 (E), 3 (F), and 5 years (G) in the validation cohort. The x axis plotted nomogram-predicted probabilities, whereas the y axis plotted observed probabilities of OS. The gray diagonal line indicated the ideal calibrated model.

Figure 4

Decision curve analysis presented the clinical net benefit between different models. Nomogram was compared with the AJCC 8th edition stage system, SII, and CA 19-9 of 1 (A), 3 (B), and 5 years (C) in the training cohort and 1 (D), 3 (E), and 5 years (F) in the validation cohort. The horizontal solid black line represented the assumption without any event. The solid gray line represented the assumption that all patients would experience the event. The dashed line showed the net benefit of models (black: nomogram, red: SII, green: CA 19-9, blue: AJCC 8th edition stage system).

Figure 5

Heterogeneities predicted by nomogram in the AJCC stage. (A) AJCC TNM stage III; (B) AJCC TNM stage IV.