AUTHOR=Wang Yanan , Qian Fangfei , Chen Ya , Yang Zhengyu , Hu Minjuan , Lu Jun , Zhang Yanwei , Zhang Wei , Cheng Lei , Han Baohui 

TITLE=Comparative Study of Pulmonary Combined Large-Cell Neuroendocrine Carcinoma and Combined Small-Cell Carcinoma in Surgically Resected High-Grade Neuroendocrine Tumors of the Lung

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.714549

DOI=10.3389/fonc.2021.714549

ISSN=2234-943X

ABSTRACT=<sec><title>Objectives</title><p>Pulmonary large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) are both classified as pure and combined subtypes. Due to the low incidence and difficult diagnosis of combined LCNEC (C-LCNEC) and combined SCLC (C-SCLC), few studies have compared their clinical features and prognosis.</p></sec><sec><title>Materials and Methods</title><p>We compared the clinical features, mutation status of driver genes (<italic>EGFR, ALK, ROS1, KRAS</italic>, and <italic>BRAF</italic>), and prognosis between C-LCNEC and C-SCLC. Univariate and multivariate Cox regression analyses were applied for survival analysis.</p></sec><sec><title>Results</title><p>We included a total of 116 patients with C-LCNEC and 76 patients with C-SCLC in the present study. There were significant differences in distribution of smoking history, tumor location, pT stage, pN stage, pTNM stage, visceral pleural invasion (VPI), and combined components between C-LCNEC and C-SCLC (<italic>P&lt;</italic>0.05 for all). C-SCLC was more advanced at diagnosis as compared to C-LCNEC. The incidence of <italic>EGFR</italic> mutations in C-LCNEC patients was higher than C-SCLC patients (25.7 <italic>vs.</italic> 5%, <italic>P</italic>=0.004). We found that tumor size, pN stage, peripheral CEA level, and adjuvant chemotherapy were independently prognostic factors for DFS and OS in C-LCNEC patients, while peripheral NSE level, pT stage, pN stage, VPI and adjuvant chemotherapy were independently associated with DFS and OS for C-SCLC patients (<italic>P&lt;</italic>0.05 for all). Propensity score matching with adjustment for the confounders confirmed a more favorable DFS (<italic>P</italic>=0.032) and OS (<italic>P</italic>=0.019) in patients with C-LCNEC in comparison with C-SCLC patients upon survival analysis.</p></sec><sec><title>Conclusions</title><p>The mutation landscape of driver genes seemed to act in different way between C-SCLC and C-LCNEC, likely by which result in clinical phenotype difference as well as better outcome in C-LCNEC.</p></sec>