A novel prognostic model to predict OS and DFS of stage II/III gastric adenocarcinoma patients in China

Abstract

Background: The prognosis of advanced gastric adenocarcinoma (GAC) after radical gastrectomy varies greatly. We aimed to build and validate a novel individualized nomogram based on inflammation index and tumor markers for patients with stage II/III GAC.

Methods: A total of 755 individuals with stage II/III GAC who had undergone radical gastrectomy at the First Affiliated Hospital of Zhengzhou University between 2012 and 2017 were included in this retrospective study. The patients were randomly divided into a training cohort (n ​= ​503) and a validation cohort (n ​= ​252). Univariate and multivariate analyses were used to determine independent prognostic factors of overall survival (OS) and disease-free survival (DFS). A nomogram was developed based on these independent factors. The concordance index (C-index) and calibration curves were used to evaluate the predictive accuracy of the nomogram.

Results: Univariate and multivariate analyses demonstrated that older age, poor differentiation, advanced stage, elevated neutrophil-to-lymphocyte ratio (NLR), lower hemoglobin, and high carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were significantly associated with lower OS and DFS and were independent prognostic factors in stage II/III GAC. The nomogram developed based on these factors in the training cohort showed excellent calibration and discrimination (OS: C-index ​= ​0.739, 95% CI ​= ​0.706-0.772; DFS: C-index ​= ​0.735, 95% CI ​= ​0.702-0.769). In the internal validation cohort, the nomogram was also well-calibrated for the prediction of OS and DFS; it was superior to the 8th edition UICC/AJCC TNM staging system (for OS: C-index ​= ​0.746 vs. 0.679, respectively; for DFS: C-index ​= ​0.736 vs. 0.675, respectively; P ​< ​0.001).

Conclusion: The nomogram model could reliably predict OS and DFS in stage II/III gastric cancer patients with radical gastrectomy. It may help physicians make better treatment decisions.

Keywords: Gastric adenocarcinoma; Inflammatory index; Nomogram; Prognosis; Tumor markers.

Figure 1

Flow diagram of the selected stage II/III GAC patients. GAC, gastric adenocarcinoma.

Figure 2

Kaplan-Meier survival plots comparing with high and low level of each indicator in the training cohort. (A–D) Survival curves of OS between high and low level of Hemoglobin, NLR, CA19-9 and CEA in stage II/III GAC patients. (E–F) Survival curves of DFS between high and low level of Hemoglobin, NLR, CA19-9 and CEA in stage II/III GAC patients. OS, overall survival; NLR, neutrophil-to-lymphocyte ratio; CA19-9, carbohydrate antigen 19-9; CEA, carcinoembryonic antigen; GAC, gastric adenocarcinoma; DFS, disease-free survival.

Figure 3

Nomogram models constructed based on the training cohort. (A) The momogram for predicting the OS rate at the 1, 2 and 3 year in stage II/III GAC patients. (B) The momogram for predicting the DFS rate at the 1, 2 and 3 year in stage II/III GAC patients. OS, overall survival; DFS, disease-free survival; GAC, gastric adenocarcinoma.

Figure 4

Time-dependent ROC curves demonstrated the ability of nomogram and TNM stage to predict 1-, 2- and 3-year OS in stage II/III GAC patients. (A–C) Time-dependent ROC curves for 1-, 2- and 3-year OS in the training cohort, (D–F) Time-dependent ROC curves for 1-, 2- and 3-year OS in the validation cohort. ROC, receiver operating characteristic curve; AUC, area under the curve; OS, overall survival; GAC, gastric adenocarcinoma.

Figure 5

Time-dependent ROC curves demonstrated the ability of nomogram and TNM stage to predict 1-,2-and 3-year DFS in stage II/III GAC patients. (A–C) Time-dependent ROC curves for 1-,2-and 3-year DFS in the training cohort, (D–F) Time-dependent ROC curves for 1-,2-and 3-year DFS in the validation cohort. ROC, receiver operating characteristic curve; AUC, area under the curve; DFS, disease-free survival; GAC, gastric adenocarcinoma.

Figure 6

Calibration plots of nomograms in both training and validation cohorts. (A) and (B) Calibration plots of 1-, 2- and 3-year OS/DFS associated nomogram in training cohort. (C) and (D) Calibration plots of 1-, 2- and 3-year OS/DFS associated nomogram in validation cohort. OS, overall survival; DFS, disease-free survival.