Development and Validation of a Nomogram for Patients with Lung Large Cell Neuroendocrine Carcinoma.

PURPOSE/OBJECTIVE(S): Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rarely high-grade neuroendocrine carcinoma of the lung with features of both small cell and non-small cell lung cancer. We aim to construct a prognostic nomogram combined with the clinical features and treatment options to predict disease-specific survival (DSS), meanwhile, evaluating the role of prophylactic cranial irradiation (PCI) in LCNEC by subgroup analysis.

MATERIALS/METHODS: A total of 713 patients diagnosed with LCNEC from the US National Cancer Institute's Surveillance Epidemiology and End Results (SEER) registry between 2010 and 2016. Cox proportional hazards analysis was conducted to choose the significant predictors of DSS. External validation was performed using 77 patients with LCNEC in the West China Hospital Sichuan University between 2010 and 2018, subgroup analysis was carried out for the whole brain radiotherapy (WBRT) and PCI population. The predictive accuracy and discriminative capability were estimated by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. The clinical applicability of the nomogram was verified through the decision curve analysis (DCA).

RESULTS: Six independent risk factors for DSS were identified and integrated into the nomogram. The nomogram achieved good C- indexes of 0.803 and 0.767 in the training and validation group respectively. Moreover, the calibration curves of both cohorts for the probability of survival showed good agreement between prediction by nomogram and actual observation in 1-, 3- and 5-year DSS. The ROC curves demonstrated the prediction accuracy of the established nomogram (all AUC>0.8). DCA confirmed the better potential clinical practicality of the nomogram in the prediction of LCNEC survival than AJCC staging. A risk classification system was built which could perfectly classify LCNEC patients into high- and low-risk groups(p<0.001). Subgroup analysis showed that WBRT did not bring survival benefits, PCI appeared to have survival benefits in LCNEC patients without brain metastases (p>0.05).

CONCLUSION: The prognostic nomogram developed in this study has certain prognostic value and clinical practicality for LCNEC patients. PCI might be investigated as a means of improving prognosis.