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

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanan Wang ◽  
Fangfei Qian ◽  
Ya Chen ◽  
Zhengyu Yang ◽  
Minjuan Hu ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Adjuvant Chemotherapy ◽  
Clinical Features ◽  
Neuroendocrine Carcinoma ◽  
Large Cell ◽  
Small Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Smoking History ◽  
Driver Genes ◽  
Pn Stage

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.

scholarly journals Molecular Characterization and Prognostication of Large Cell Neuroendocrine Carcinoma and Large Cell Carcinoma

2022 ◽  
Vol 11 ◽  
Author(s):  
Ying Chen ◽  
Xiaoying Cui ◽  
Di Wang ◽  
Guojie Xia ◽  
Minyan Xing ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Cell Carcinoma ◽  
Neuroendocrine Carcinoma ◽  
Large Cell Carcinoma ◽  
Large Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Gene Panel ◽  
Smoking History ◽  
Study Cohort ◽  
Poor Outcome

PurposeLarge cell neuroendocrine carcinoma (LCNEC) and classic large cell carcinoma (LCC) are two distinct entities with different histological and biological characteristics. However, the mutational profiles and the clinical behavior of the two subtypes of lung cancer remain to be explored.Patients and MethodsPathological diagnoses of all screened patients were finally confirmed by three or four experienced pathologists. Patients with uncertain pathological diagnoses were excluded. Finally, we genetically profiled ten patients with LCNEC and seven with LCC. ALL patients were subjected to next-generation sequencing (NGS) test, which included nine patients sequenced with a 139-gene panel and eight patients with a 425-gene panel. Including only intersected mutations from these two panels, survival analysis was further conducted.ResultsBoth LCNEC and LCC showed high prevalence in male patients, with no clear association with smoking history. Potential targetable mutations in KRAS and RET were detected in the study cohort. However, LCNEC and LCC showed distinct mutational profiles with an enrichment of RB1/TP53 co-mutations in a subset of LCNEC patients. SMARCA4 and KEAP1 mutations were exclusively found in LCC patients, and RICTOR, BRAF, ROS1 and TET2 mutations were only detected in LCNEC. LCC patients in the cohort had shorter survival compared to LCNEC patients (p=0.006). Survival analysis revealed an association between SMARCA4 mutations and poor outcome in the study cohort and in the LCC subset. Mutations in BRAF were associated with a trend of increased survival in the study cohort, as well as in the LCNEC subset. Finally, TET2 mutations were associated with poor outcome in the LCNEC cohort.ConclusionLCC and LCNEC were both heterogeneous diseases with limited treatment options. Our study identified potential targetable mutations and prognostic biomarkers that might provide more therapeutic options and improve individualized patient care.

scholarly journals Clinical Features and Outcomes Analysis of Surgical Resected Pulmonary Large-Cell Neuroendocrine Carcinoma With Adjuvant Chemotherapy

2020 ◽  
Vol 10 ◽  
Author(s):  
Yinchen Shen ◽  
Fang Hu ◽  
Changhui Li ◽  
Jianlin Xu ◽  
Runbo Zhong ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Clinical Features ◽  
Neuroendocrine Carcinoma ◽  
Large Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Tumor Relapse ◽  
Serum Carcinoembryonic Antigen ◽  
Serum Cea ◽  
N Stage

ObjectiveLarge-cell neuroendocrine carcinoma (LCNEC) is a rare subtype of pulmonary cancer with poor survival. Optimal adjuvant chemotherapy for resected LCNEC is controversial till now; clinical features together with the prognostic factors in LCNEC should be clarified better.MethodsClinicopathological characteristics, driven genes’ status (EGFR, ALK, and ROS1), adjuvant chemotherapy strategy for 94 surgical resected LCNECs were extracted from digital database, tumor relapse or progression, and survival were analyzed with clinical profiles.ResultsDriven gene mutants were scarce in LCNEC, 8.3% (4/48) samples harbored EGFR mutations, 5.8% (3/52) with ALK positive, and none of ROS1 positive. A total of 44 patients suffered tumor relapse or progression during follow-up. Tumor/lymph node (N) stage, serum carcinoembryonic antigen (CEA) level before surgery, different adjuvant chemotherapies were associated with tumor relapse (P < 0.05); poorer disease-free survival (DFS) appeared in N2/stage III, serum CEA positive and pemetrexed based chemotherapy (P < 0.05); for overall survival (OS) analysis, the T/tumor stage, serum positive CEA/neuron-specific enolase (NSE) at baseline were associated with worse OS (P < 0.05). Moreover, in the multivariate analysis, N stage still acted as prognostic for DFS (P = 0.019); OS differed significantly in different T stages, chemotherapy selection and serum CEA levels after adjustment (P < 0.05).ConclusionClassical driven gene mutations were rare in LCNEC. Tumor N stage appeared as prognostic for DFS, while serum positive CEA, different adjuvant chemotherapy strategies, and T stage were independent prognostic factors for OS. Etoposide–platinum regime seemed to be a better choice which should be confirmed by further prospective investigations.

scholarly journals Effect of Adjuvant and Palliative Chemotherapy in Large Cell Neuroendocrine Carcinoma of the Lung: A Systematic Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5948
Author(s):  
Hao Chen ◽  
Masashi Ishihara ◽  
Nobuyuki Horita ◽  
Hiroki Kazahari ◽  
Ryusuke Ochiai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Adjuvant Chemotherapy ◽  
Neuroendocrine Carcinoma ◽  
Palliative Chemotherapy ◽  
Meta Analysis ◽  
Large Cell ◽  
Small Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Small Cell Lung

Background: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subset of lung carcinoma with poor overall survival. Methods: A systematic review following a meta-analysis of studies was performed to identify the effect of different selections of chemotherapy in LCNEC. Articles providing overall survival data for adjuvant chemotherapy or palliative chemotherapy for LCNEC were eligible. The odds ratio (OR) of mortality at one or two years after chemotherapy was evaluated. Results: A total of 16 reports were finally included in the quantitative synthesis, involving a total of 5916 LCNEC patients. Adjuvant chemotherapy was administered to 1303 patients, and palliative chemotherapy was administered to 313 patients using either a small cell lung cancer (SCLC) or a non-small cell lung cancer (NSCLC) regimen. The OR for adjuvant chemotherapy was 0.73 (95% confidence interval (CI): 0.59 to 0.89, p = 0.002). The SCLC regimen showed an OR of 0.52 (95% CI: 0.11 to 2.38, p = 0.40) after one year, and 0.32 (95% CI: 0.11 to 0.89, p = 0.03) after two years, compared with the NSCLC regimen. Conclusions: Adjuvant chemotherapy for pulmonary large cell neuroendocrine carcinoma improved the outcome after surgery. The SCLC regimen showed better survival than the NSCLC regimen as palliative chemotherapy.

Clinical Features of Pulmonary Large Cell Neuroendocrine Carcinoma

2003 ◽  
Vol 35 (3) ◽  
pp. 245-253
Author(s):  
Moo Suk Park ◽  
Kil Dong Kim ◽  
Jae Ho Chung ◽  
Dong Hwan Shin ◽  
Kyung Young Chung ◽  
...  
Keyword(s):  
Clinical Features ◽  
Neuroendocrine Carcinoma ◽  
Large Cell ◽  
Large Cell Neuroendocrine Carcinoma

scholarly journals CDX2 Expression and Prognostic Factors of Resectable Pulmonary Large Cell Neuroendocrine Carcinoma

2020 ◽  
Vol 14 ◽  
pp. 117955492096731
Author(s):  
Ryo Mori ◽  
Shin-ichi Yamashita ◽  
Kensuke Midorikawa ◽  
Sosei Abe ◽  
Kazuo Inada ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Prognostic Factor ◽  
Neuroendocrine Carcinoma ◽  
Vascular Invasion ◽  
Cox Regression ◽  
Large Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Clinicopathological Factors ◽  
Cdx2 Expression

Background and Aim: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare neoplasm, and its clinical features and management are still limited. We evaluated the clinicopathological factors, including CDX2 immunohistochemical expression, to predict survival in patients with LCNEC. Patients and Methods: In all, 50 patients with LCNEC who underwent surgery at 4 institutes between 2001 and 2017 were included. Clinicopathological characteristics were evaluated for prognostic factors and statistically analyzed by Kaplan-Meier curve with a log-rank test or Cox regression models. We used immunohistochemical (IHC) analysis to determine the expressions of CDX2 and compared them with clinicopathological factors and survival. Results: Sixteen of the 50 cases (32%) were CDX2 positive. No correlation was found between the CDX2 expression by IHC and clinicopathological factors. Multivariate analysis identified adjuvant chemotherapy (hazard ratio [HR] =2.86, 95% confidence interval [CI] = 1.04-8.16, P = .04) and vascular invasion (HR = 4.35, 95% CI = 1.21-15.63, P = .03) as being associated with a significantly worse rate of recurrence-free survival. Conclusion: CDX2 was expressed in 1/3 of LCNEC but not associated with prognostic factor. Adjuvant chemotherapy and vascular invasion were associated with a negative prognostic factor of LCNEC.

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