Search

BACKGROUND: Combined small-cell lung cancer (CSCLC) refers to the simultaneous presence of small cell lung cancer (SCLC) and any subtype of the non-small cell lung cancer (NSCLC). This study aimed to explore the prognosis of CSCLC, NSCLC, and pure SCLC patients, and to develop a nomogram to estimate the overall survival (OS) for CSCLC patients. METHODS: Patients diagnosed with NSCLC, CSCLC, and pure SCLC between 2004 and 2015 were identified from the Surveillance Epidemiology and End Results (SEER) database. Survival analyses were performed by using the Kaplan Meier curves and Cox proportional hazards regression. All CSCLC patients were randomly split 7:3 into training and validation sets. A nomogram was developed by integrating all independent predictors for OS. The performance of the nomogram was determined by discrimination, calibration ability, clinical usefulness, and risk stratification ability. RESULTS: A total of 326,695 lung cancer patients, including 871 with CSCLC, 280,391 with NSCLC, and 45,433 with pure SCLC were enrolled. CSCLC was associated with worse survival compared with NSCLC both in the unmatched and matched cohorts. However, compared to pure SCLC, CSCLC was associated with significantly better survival in the unmatched cohorts only, while showed marginally non-significantly better survival after propensity score matching (PSM). For CSCLC, a nomogram was constructed for the 6-month, 1-year, and 3-year OS prediction by combining the independent risk factors, including age, gender, tumor, node, and metastasis stage, surgery, and chemotherapy. The nomogram showed good discrimination and calibration both in the training and validation sets, and better performance than the tumor–node–metastasis staging system. Risk stratification analysis indicated that the nomogram scores efficiently divided CSCLC patients into low-, intermediate-, and high-risk groups (P

Background Combined small cell lung cancer (CSCLC) is an uncommon and heterogeneous subtype of small cell lung cancer (SCLC). However, there is limited data concerning the different molecular changes and clinical features in CSCLC compared to pure SCLC. Methods The clinical and pathological characteristics of pure SCLC and CSCLC patients were analyzed. Immunohistochemistry and microdissection were performed to isolate the CSCLC components. Further molecular analysis was carried out by next-generation sequencing (NGS) in 12 CSCLC and 30 pure SCLC. Results There were no significant differences in clinical features between CSCLC and pure SCLC. Overall survival (OS) of CSCLC patients was worse than pure SCLC (P=0.005). NGS results indicated that TP53 and RB1 were the most frequently mutated genes in both CSCLC (83.33% and 66.67%) and pure SCLC (80.00% and 63.33%) groups. However, less than 10% common mutations were found in both CSCLC and pure SCLC. When analyzing the data of SCLC and non-small cell lung cancer (NSCLC) components of CSCLC, more than 50% common mutations, and identical genes with mutations were detected. Moreover, there were also common biological processes and signaling pathways identified in CSCLC and pure SCLC, in addition to SCLC and NSCLC components. Conclusions There were no significant differences in terms of clinical features between CSCLC and pure SCLC. However, the prognosis for CSCLC was worse than pure SCLC. NGS analysis suggested that CSCLC components might derive from the same pluripotent single clone with common initial molecular alterations and subsequent acquisitions of other genetic mutations.