Abstract
ObjectivesPulmonary 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.Materials and MethodsWe compared the clinical features, mutation status of driver genes (EGFR, ALK, ROS1, KRAS, and BRAF), and prognosis between C-LCNEC and C-SCLC. Univariate and multivariate Cox regression analyses were applied for survival analysis.ResultsWe 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 (P<0.05 for all). C-SCLC was more advanced at diagnosis as compared to C-LCNEC. The incidence of EGFR mutations in C-LCNEC patients was higher than C-SCLC patients (25.7 vs. 5%, P=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 (P<0.05 for all). Propensity score matching with adjustment for the confounders confirmed a more favorable DFS (P=0.032) and OS (P=0.019) in patients with C-LCNEC in comparison with C-SCLC patients upon survival analysis.ConclusionsThe 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.
Highlights
Neuroendocrine carcinoma of the lung, which accounts for about 15–20% of primary lung cancer, is divided into four categories: small-cell lung cancer (SCLC), typical carcinoid, atypical carcinoid, and large-cell neuroendocrine carcinoma (LCNEC) [1, 2]
We evaluated EGFR mutations by amplification refractory mutation system (ARMS) method, ALK expression by immunohistochemistry (IHC), ROS1 fusion by in situ hybridization (FISH), and KRAS/BRAF mutations by polymerase chain reaction (PCR) amplification method
We found that tumor size, pN stage, peripheral CEA level, and adjuvant chemotherapy were independently associated with Disease-free survival (DFS) and Overall survival (OS) in combined LCNEC (C-LCNEC) patients (Figure 3)
Summary
Neuroendocrine carcinoma of the lung, which accounts for about 15–20% of primary lung cancer, is divided into four categories: small-cell lung cancer (SCLC), typical carcinoid, atypical carcinoid, and large-cell neuroendocrine carcinoma (LCNEC) [1, 2]. C-SCLC is defined as a SCLC type that is mixed with other components of non-small-cell lung cancer (NSCLC), such as adenocarcinoma (AD), squamous cell carcinoma (SCC), largecell carcinoma (LCC), LCNEC, and so on. Owing to the rarity and the difficulty in diagnosis of C-LCNEC and C-SCLC, it is lack of the statistical description of their clinical features, genomic landscape, prognosis, and the relevant comparisons. No large sample studies up to now have compared C-LCNEC with C-SCLC in terms of clinical features and genomic mutation landscape. We conducted this study to fill this gap and wish the results may provide new insights into the treatment of resected C-LCNEC and C-SCLC
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call