Clinical Prediction Nomograms to Assess Overall Survival and Disease-Specific Survival of Patients with Salivary Gland Adenoid Cystic Carcinoma

Abstract

Aim: Salivary gland adenoid cystic carcinoma (SACC) is the second highest incidence of malignant salivary gland tumor. The purpose of this study was to establish nomograms combined with SACC patients based on the Surveillance, Epidemiology, and End Results (SEER) database.

Methods: Patients with SACC were included in the SEER∗Stat Database from 2004 to 2016. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to filter potential prognostic clinical variables. Multivariate analysis from the Cox proportional hazards model was performed to determine the independent prognostic factors on overall survival (OS) and disease-specific survival (DSS), applied to develop nomograms. The Schönfeld residual test verified the proportional hazard assumption. The discrimination and consistency of nomograms was assessed and validated according to concordance index (C-index), receiver operating characteristic (ROC) curves, and calibration curves using an internal 1,000 times bootstrap resampling. The nomogram's net clinical benefit was assessed through decision curve analysis (DCA).

Results: A total of 658 patients with SACC were included. Age, T stage, N stage, M stage, histologic grade, and surgery were independent prognostic factors for OS and DSS. Based on these independent prognostic factors, nomograms were developed to predict 3-, 5-, and 10-year OS and DSS. In the validation of 1,000 times bootstrap resampling, the C-index and ROC curves had good discriminatory ability. The calibration curves indicated excellent consistency between the predicted and actual survival results in the nomograms. The DCA curves demonstrated that the nomograms had good clinical benefit and were superior to the TNM stage and other variables.

Conclusions: Two nomograms developed in this study precisely predicted the 3-, 5-, and 10-year OS and DSS rates of patients with SACC in accordance with independent prognostic factors, and their clinical value is better than TNM staging, providing a prognostic reference for other SACC patients.

Figure 1

The flowchart displaying the selection process of patients with SACC from the SEER∗Stat Database. SACC: salivary gland adenoid cystic carcinoma; SEER: Surveillance, Epidemiology, and End Results.

Figure 2

Used LASSO COX regression model to filter predictor variables for OS and DSS. (a) Selection of lambda.1se identified 6 variables for OS in LASSO Cox analysis. (b) LASSO coefficient profiles of 13 variables for OS. (c) Selection of lambda.1se identified 5 variables for DSS in LASSO Cox analysis. (d) LASSO coefficient profiles of 13 variables for DSS. Notes—1: age, 2: gender, 3: primary site of tumor, 4: histologic grade, 5: T stage, 6: N stage, 7: M stage, 8: race, 9: marital status, 10: surgery, 11: radiation, 12: chemotherapy, and 13: neck dissection.

Figure 3

The pH assumption that met the cox proportional hazards model of OS (a) and DSS (b) verified by the Schönfeld residual test.

Figure 4

Construction of nomograms. (a) Nomogram predicting 3-, 5-, and 10-year OS in patients with SACC from SEER∗Stat Database between 2004 and 2016. (b) Nomogram predicting 3-, 5-, and 10-year DSS in patients with SACC from SEER∗Stat Database between 2004 and 2016.

Figure 5

Validation of nomograms. (a) The ROC curves of the nomogram for predicting 3-, 5-, and 10-year OS; the area under curve was 0.822, 0.836, and 0.830, respectively. (b) The ROC curves of the nomogram for predicting 3-, 5-, 10-year DSS; the area under curve was 0.838, 0.846, and0.847, respectively. Calibration curves of the nomogram for predicting (c) 3-, (d) 5-, and (e) 10-year OS and the actual OS. Calibration curves of the nomogram for predicting (f) 3-, (g) 5-, and (h) 10-year DSS and the actual DSS.

Figure 6

DCA curves of the nomograms and other independent prognostic factors. The DCA curves of the nomogram for predicting (a) 3- and (b) 5-year OS had a better net benefit compared to other independent prognostic factors. The DCA curves of the nomogram for predicting (c) 3- and (d) 5-year DSS showed better net benefit compared with other independent prognostic factors.