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

doi:10.3389/fonc.2021.692647

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

Front Oncol. 2021 Jun 29:11:692647. doi: 10.3389/fonc.2021.692647. eCollection 2021.

Authors

Lin Li^{1

2

3

4}, Tai Ren^{1

2

3}, Ke Liu^{1

2

3

4}, Mao-Lan Li^{2

3

4}, Ya-Jun Geng^{1

2

3

4}, Yang Yang^{1

2

3

4}, Huai-Feng Li^{2

3

4}, Xue-Chuan Li^{1

2

3

4}, Run-Fa Bao^{2

3

4}, Yi-Jun Shu^{2

3

4}, Hao Weng^{2

3

4}, Wei Gong^{2

3

4}, Wan Yee Lau⁵, Xiang-Song Wu^{2

3

4}, Ying-Bin Liu^{1

2

3

6}

Affiliations

¹ Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China.
³ Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China.
⁴ Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, Hong Kong.
⁶ Shanghai Cancer Institute, State Key Laboratory of Oncogenes and Related Genes, Shanghai, China.

Abstract

Objectives: To 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.

Methods: Based 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.

Results: Of 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.

Conclusions: SII 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).

Keywords: chemotherapy; gallbladder carcinoma; nomogram; prognostic marker; systemic immune-inflammation index.

Associated data

ClinicalTrials.gov/NCT04140552