Construction and validation of nomograms based on the log odds of positive lymph nodes to predict the prognosis of lung neuroendocrine tumors

Abstract

Background: This research aimed to investigate the predictive performance of log odds of positive lymph nodes (LODDS) for the long-term prognosis of patients with node-positive lung neuroendocrine tumors (LNETs).

Methods: We collected 506 eligible patients with resected N1/N2 classification LNETs from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The study cohort was split into derivation cohort (n=300) and external validation cohort (n=206) based on different geographic regions. Nomograms were constructed based on the derivation cohort and validated using the external validation cohort to predict the 1-, 3-, and 5-year cancer-specific survival (CSS) and overall survival (OS) of patients with LNETs. The accuracy and clinical practicability of nomograms were tested by Harrell's concordance index (C-index), integrated discrimination improvement (IDI), net reclassification improvement (NRI), calibration plots, and decision curve analyses.

Results: The Cox proportional-hazards model showed the high LODDS group (-0.79≤LODDS) had significantly higher mortality compared to those in the low LODDS group (LODDS<-0.79) for both CSS and OS. In addition, age at diagnosis, sex, histotype, type of surgery, radiotherapy, and chemotherapy were also chosen as predictors in Cox regression analyses using stepwise Akaike information criterion method and included in the nomograms. The values of C-index, NRI, and IDI proved that the established nomograms were better than the conventional eighth edition of the TNM staging system. The calibration plots for predictions of the 1-, 3-, and 5-year CSS/OS were in excellent agreement. Decision curve analyses showed that the nomograms had value in terms of clinical application.

Conclusions: We created visualized nomograms for CSS and OS of LNET patients, facilitating clinicians to bring individually tailored risk assessment and therapy.

Keywords: log odds of positive lymph nodes; lung neuroendocrine tumor; nomogram; predictor; survival.

Figure 1

Selection of study cohort from the SEER database. AC, atypical carcinoid; LCNEC, large cell neuroendocrine carcinoma; SCLC, small cell lung carcinoma; SEER, Surveillance, Epidemiology, and End Results; LN, lymph node; TNM, tumor-node-metastasis.

Figure 2

Nomograms and quick response codes of the webservers of the nomograms to predict 1-, 3- and 5-year CSS (A) and OS (B) for patients with node-positive lung neuroendocrine carcinoma after surgery. CSS, lung cancer-specific survival; OS, overall survival; LODDS, log odds of positive lymph nodes.

Figure 3

Calibration plots of the nomograms to predict CSS and OS of the derivation dataset (A, B) and external validation dataset (C, D). CSS, lung cancer-specific survival; OS, overall survival.

Figure 4

ROC curves of the nomograms and TNM staging system for predicting 1-, 3-, 5-year CSS in the derivation dataset (A–C) and external validation dataset (D–F), and 1-, 3-, 5-year OS in the derivation dataset (G–I) and external validation dataset (J–L). ROC, receiver operating characteristic; CSS, lung cancer-specific survival; OS, overall survival.

Figure 5

DCA of the nomograms and TNM staging system for predicting 1-, 3-, 5-year CSS in the derivation dataset (A–C) and external validation dataset (D–F), and 1-, 3-, 5-year OS in the derivation dataset (G–I) and external validation dataset (J–L). DCA, decision curve analysis; CSS, lung cancer-specific survival; OS, overall survival.

Figure 6

Kaplan-Maier curves comparing nomogram-based classification with 8th AJCC TNM staging system in CSS (A, B) and OS (C, D) prediction. CSS, cancer-specific survival; OS, overall survival.