Risk factors, survival analysis, and nomograms for distant metastasis in patients with primary pulmonary large cell neuroendocrine carcinoma: A population-based study

Abstract

Introduction: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rapidly progressive and easily metastatic high-grade lung cancer, with a poor prognosis when distant metastasis (DM) occurs. The aim of our study was to explore risk factors associated with DM in LCNEC patients and to perform survival analysis and to develop a novel nomogram-based predictive model for screening risk populations in clinical practice.

Methods: The study cohort was derived from the Surveillance, Epidemiology, and End Results database, from which we selected patients with LCNEC between 2004 to 2015 and formed a diagnostic cohort (n = 959) and a prognostic cohort (n = 272). The risk and prognostic factors of DM were screened by univariate and multivariate analyses using logistic and Cox regressions, respectively. Then, we established diagnostic and prognostic nomograms using the data in the training group and validated the accuracy of the nomograms in the validation group. The diagnostic nomogram was evaluated using receiver operating characteristic curves, decision curve analysis curves, and the GiViTI calibration belt. The prognostic nomogram was evaluated using receiver operating characteristic curves, the concordance index, the calibration curve, and decision curve analysis curves. In addition, high- and low-risk groups were classified according to the prognostic monogram formula, and Kaplan-Meier survival analysis was performed.

Results: In the diagnostic cohort, LCNEC close to bronchus, with higher tumor size, and with higher N stage indicated higher likelihood of DM. In the prognostic cohort (patients with LCNEC and DM), men with higher N stage, no surgery, and no chemotherapy had poorer overall survival. Patients in the high-risk group had significantly lower median overall survival than the low-risk group.

Conclusion: Two novel established nomograms performed well in predicting DM in patients with LCNEC and in evaluating their prognosis. These nomograms could be used in clinical practice for screening of risk populations and treatment planning.

Keywords: Large cell neuroendocrine carcinoma (LCNEC); distant metastasis (DM); nomogram; predictive model; the Surveillance, Epidemiology, and End Results (SEER) database.

Figure 1

A diagnostic nomogram was developed for predicting the risk of distant metastasis in patients with LCNEC (A). The receiver operating characteristic (ROC) curve (B), decision curve analysis (DCA) curve (C), and the GiViTI calibration belt (D) of the training group, and the ROC curve (E), DCA curve (F), and the GiViTI calibration belt (G) of the validation group were used to evaluate the validity and reliability of the nomogram.

Figure 2

The area under the receiver operating characteristic curves (AUCs) were compared for the diagnostic nomogram in the training group (A) and validation group (B) with all independent variables, including N stage, primary site, and tumor size.

Figure 3

A prognostic nomogram was developed for predicting the 1-, 2-, and 3-year OS of patients with LCNEC with distant metastasis.

Figure 4

The decision curve analysis (DCA) curves at 1 (A), 2 (B), and 3 years (C) and the calibration curves at 1 (D), 2 (E), and 3 years (F) in the training group were used to evaluate the reliability of the prognostic nomogram.

Figure 5

The decision curve analysis (DCA) curves at 1 (A), 2 (B), and 3 years (C) and the calibration curves at 1 (D), 2 (E), and 3 years (F) in the validation group were used to evaluate the reliability of the prognostic nomogram.

Figure 6

The time-dependent receiver operating characteristic (ROC) curves at 1, 2, and 3 years in the training group (A) and in the validation group (B) were used to evaluate the validity of the prognostic nomogram.

Figure 7

The area under the receiver operating characteristic curves (AUCs) were compared for the prognostic nomogram in the training and validation groups with all independent variables, including Sex, N stage, Surgery, and Chemotherapy at 1 (A, D), 2 (B, E), and 3 years (C, F).

Figure 8

Survival outcomes in the training group (A) and validation group (B) for the high-risk and low-risk groups (according to the prognostic nomogram formula).