| Part I:Clinicopathological characteristics,survival outcomes and prognostic factors of pulmonary large cell neuroendocrine carcinomaBackground: Pulmonary large cell neuroendocrine carcinoma(LCNEC)is a subtype of lung cancer.LCNEC has similar neuroendocrine morphology with small cell lung carcinoma(SCLC),however molecular profling identified by next-generation sequencing suggested that LCNEC has both SCLC-like subset and NSCLC-like subset.In addition,there are conflicting reports about the chemotherapy regimen and survival outcomes of LCNEC.Only some small samples clinical trials were undertook because of its low incidence.In this study,a large population-based retrospective study was undertook to compare the clinicopathological characteristics,survival outcomes and metastatic patterns between LCNEC and other non-small cell lung cancers(ONSCLC)and to identify the prognostic factors of LCNEC.Methods: Patients diagnosed with LCNEC and ONSCLC from 2004 to 2014 were enrolled from the Surveillance,Epidemiology,and End Results(SEER)dataset.Pearson’s Chi-square tests were used to compare the differences in clinicopathological characteristics.The Kaplan-Meier method was used for survival analysis.Propensity score was used for matching,and Cox proportional hazards model was used for multivariate analysis and subgroup analysis.Results: A total of 2368 LCNEC cases and 231672 ONSCLC cases were identified.Except for marital status,LCNEC patients had obviously different biological features from ONSCLC patients.Survival analysis showed that the median lung cancer-specific survival(m LCSS)of LCNEC was 10.0 months,the m LCSS of ONSCLC was 13.0 months.The median overall survival(m OS)of LCNEC was 9.0 months,the m OS of ONSCLC was 11.0 months.The survial outcomes of LCNEC were still worse than ONSCLC after balancing the clinicopathological characteristics by propensity score matching.Female gender,black race,surgery,radiation and chemotherapy were protective factors for LCNEC in the multivariate analysis.Matched subgroup analysis further demonstrated that most subgroup factors favored ONSCLC,especially early stage.Early-stage LCNEC patients had a higher risk of lung cancer-specific death than did early-stage ONSCLC patients.Moreover,metastatic patterns were different between LCNEC and ONSCLC.For LCNEC,the most common single site,two-site,three-site metastatic pattern was brain(22.25%),bone and liver(4.67%),bone and brain and liver(2.10%),respectively.For ONSCLC,that was bone(16.75%),bone and lung(2.66%),bone and lung and liver(1.11%),respectively.The rate of four-site combined metastases(including bone,brain,liver and lung)of LCNEC and ONSCLC was 0.39% and 0.57%,respectively.Subgroup analysis suggested that patients with isolated liver metastasis experienced poor survival.Conclusions: LCNEC has totally different clinicopathological characteristics and metastatic patterns from ONSCLC.The survival outcomes of LCNEC were inferior to ONSCLC.Part II: Prediction model of pulmonary large cell neuroendocrine carcinomaObjective: To construct a nomogram prediction model of LCNEC base on the large-population database.Methods: Patients diagnosed with LCNEC between 2004 and 2013 were collected from the SEER database.Cox proportional hazard model was used to evaluate the factors related to overall survival.Then,significant factors were used to construct a nomogram prediction model.The discrimination of this model was evaluated by C-index,the calibration was evaluated by a bootstrap procedure.Results: A total of 1656 LCNEC patients with full clinical characteristics information were enrolled.Male patients accounted for 55.37%.Patients with age ≥ 65 at diagnosis accounted for 52.05%.Most patients(84.12%)were white race.In addition,51.93% of total patients had chemotherapy history,40.94% had surgery,but only 37.80% had radiation therapy.In the multivariate analysis,female,black race,surgery,radiation and chemotherapy were protective factors,while age ≥ 65,increased tumor size,regional direct extension,lymph nodes infiltration and distant metastasis were risk factors.No significant difference was found between different primary tumor sites.Furthermore,a nomogram prediction model was constructed for predicting 1-year survival probability based on the significant factors in the multivariate analysis.The C-index of the prediction model was 0.76,the assessment of calibration found that the predicted 1-year survival rate was almost identical to the actual observed 1-year survival rate.Conclusions: A nomogram prediction model was constructed for predicting 1-year survival probability for LCNEC based on SEER database,which could be a useful tool for clinical decision-making. |
