Development and Validation of a Prognostic Nomogram Based on the Systemic Immune-Inflammation Index for Resectable Gallbladder Cancer to Predict Survival and Chemotherapy Benefit.

Lin Li,Tai Ren,Wan Yee Lau,Hao Weng,Yang Yang,Mao-Lan Li,Run-Fa Bao,Xue-Chuan Li,Ying-Bin Liu,Huai-Feng Li,Ke Liu,Wei Gong,Xiang-Song Wu,Ya-Jun Geng,Yi-Jun Shu

doi:10.3389/fonc.2021.692647

Abstract

ObjectivesTo investigate the prognostic significance of the systemic immune-inflammation index (SII) in patients after radical cholecystectomy for gallbladder cancer (GBC) using overall survival (OS) as the primary outcome measure.MethodsBased on data from a multi-institutional registry of patients with GBC, significant prognostic factors after radical cholecystectomy were identified by multivariate Cox proportional hazards model. A novel staging system was established, visualized as a nomogram. The response to adjuvant chemotherapy was compared between patients in different subgroups according to the novel staging system.ResultsOf the 1072 GBC patients enrolled, 691 was randomly selected in the discovery cohort and 381 in the validation cohort. SII>510 was found to be an independent predictor of OS (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.42-2.54). Carbohydrate antigen 199(CA19-9), tumor differentiation, T stage, N stage, margin status and SII were involved in the nomogram. The nomogram showed a superior prediction compared with models without SII (1-, 3-, 5-year integrated discrimination improvement (IDI):2.4%, 4.1%, 5.4%, P<0.001), and compared to TNM staging system (1-, 3-, 5-year integrated discrimination improvement (IDI):5.9%, 10.4%, 12.2%, P<0.001). The C-index of the nomogram in predicting OS was 0.735 (95% CI 0.683-0.766). The novel staging system based on the nomogram showed good discriminative ability for patients with T2 or T3 staging and with negative lymph nodes after R0 resection. Adjuvant chemotherapy offered significant survival benefits to these patients with poor prognosis.ConclusionsSII was an independent predictor of OS in patients after radical cholecystectomy for GBC. The new staging system identified subgroups of patients with T2 or T3 GBC with negative lymph nodes who benefited from adjuvant chemotherapy.Clinical Trial Registration ClinicalTrials.gov, identifier (NCT04140552).

Highlights

Gallbladder cancer (GBC) is a highly malignant tumor that accounts for 80%-95% of biliary tract malignancies [1]
The inclusion criteria were as following [1]: pathologically diagnosed GBC according to International Classification of Disease for Oncology (ICD-O3); [2] data containing detailed preoperative blood results; [3] radical cholecystectomy performed for GBC
The following predictors were associated with worse overall survival (OS): age, CA19-9>40 U/ml, total bilirubin>35 μmol/L, more advanced surgical approach, R1 resection margin status, pathological type, poor tumor differentiation, microvascular invasion, perineural invasion, advanced T staging, advanced N staging, platelet-to-lymphocyte ratio (PLR)>144, neutrophil-to-lymphocyte ratio (NLR)>2.3, LMR>10, and systemic immune-inflammation index (SII)>510 (Table 2)

Summary

Introduction

Gallbladder cancer (GBC) is a highly malignant tumor that accounts for 80%-95% of biliary tract malignancies [1]. American Joint Committee on Cancer(AJCC; eighth version) TNM Staging System is the most widely used system for GBC [3]. Accumulating evidences have suggested that the inflammation pathway is closely related to tumor development and progression [6,7,8]. Inflammatory indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and Glasgow prognostic score (GPS) have been proven to have prognostic values for GBC [9,10,11]. The systemic immune-inflammation index (SII), which is based on neutrophil, lymphocyte and platelet counts as first described in hepatocarcinoma cancer [12], has rarely been studied in GBC [13]

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