Background Transformation to a lung neuroendocrine tumor (LNET) is a mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI). Serum neuron-specific enolase (NSE) is a useful marker in the detection of LNET. Therefore, we explored the clinical significance of serum NSE levels in the detection of transformed neuroendocrine tumors after EGFR-TKI therapy. Methods We report a cohort of 5 cases in our treatment group. The characteristics of the patients, pathological diagnoses, immunohistochemistry with molecular detection, laboratory examination, and treatment histories are analyzed. The tumor markers of serum NSE were analyzed. Additionally, we reviewed the publications reporting the tumor markers before and after LNET transformation during EGFR-TKI therapy. Results Most patients are female (3/5), aged <60 years old (4/5), nonsmokers (4/5) and harbor the EGFR 19 exon deletion (4/5). The median time of LNET transformation was 19 months (range: 12–31 months). The clinical characteristics were similar to those reported in previous studies. Laboratory examination revealed an increased NSE level before the LNET is defined. Sixteen publications were reviewed. Of those, 86.67% (13/15) publications showed an increased level of NSE when the LNET transformation was defined. Conclusion Adenocarcinoma tumors in non-smokers, young patients harboring the EGFR 19 exon deletion tended to transform to LNETs after EGFR-TKI therapy. Combining our findings and a review of the literature, we suggest that serum NSE may be a useful tumor marker to predict neuroendocrine tumor transformation.

Background: Surgery is recognized as an important part of treating stage I-IIA small cell lung cancer (SCLC), but few studies have explored the predictive factors for overall survival (OS) or time to tumor progression (TTP). This paper aims to explore the predictive factors related to improved overall and relapse-free survival. Methods: Patients with stage I-IIA SCLC were reviewed between January 1st, 2014, and December 30th, 2016, at the Shanghai Chest Hospital. Basic patient characteristics and clinical data were collected, including age, sex, tumor (T) stage, pathological characteristics, and treatment. Patient follow-ups were conducted by checking medical records or phoning the patient, with survival data and instances of recurrence and/ or metastasis being collected and recorded. Univariate and multivariate analyses were used to identify the predictive factors.Results: A total of 59 patients were enrolled in this study, and the median follow-up duration was 53.7 months. The 3-year disease free and 3-year OS rates were 62.5% and 75.0%, respectively. The 5-year disease free and 5-year OS rates were not reached. Univariate and multivariate analyses revealed that a higher T stage [hazard ratio (HR) 3.210, P=0.048], the presence of tumor thrombosis (HR 6.021, P=0.043), and the absence of adjuvant chemotherapy (HR 3.425, P=0.059) were more reflective of shorter TTP than other factors, with the presence of adjuvant chemotherapy also correlating with improved OS. Conclusions:A patient having a T1 stage with no tumor thrombus and receiving adjuvant chemotherapy were observed as positive factors for longer periods of TTP, and adjuvant chemotherapy was a favorable predictor for the OS of patients with resected stage I-IIA SCLC.

Introduction: BRAF mutations occur 1%-4% in nonesmall-cell lung cancer, and the natural history of tumors harboring these mutations remains an area of ongoing study. The aim of this retrospective study was to describe the natural history, occurrence of co-mutations and clinical outcomes in patients with BRAF-mutated NSCLC. Methods: Patients with BRAF-mutated NSCLC seen at Affiliated cancer hospital of Zhengzhou university from January 1, 2017 through December 31, 2019 were reviewed. The Kaplan-Meier method was used to calculate median progression free survival (PFS) and median overall survival, and the COX regression model was established to analyze the association between the overall survival and various factors. Results: NGS (Next Generation Sequencing) data of either plasma or tissue samples obtained from 3217 Chinese stage I-IV NSCLC patients were retrospectively analyzed, 46 (1.4%) patients were found to have BRAF mutation, including 35(76%) V600E mutation and 11non-V600E mutation. Concomitant mutations had been also discovered, it's a more tendency for V600E mutation to had a concomitant mutation, Among 35 NSCLC with V600E mutation, 2 had a concomitant mutation in EGFR 19 exon deletion,1 in EGFR 21exon L858R mutation,1 inTP53 mutation and 1 in PIK3CA mutation; However, in the 11 non-V600E mutation, no concomitant mutation was found, but 2 with MET amplification. Clinical and pathological features were similar between patients with V600E vs non-V600E mutations.The average age was 62 years old ( 43-84). 25(54%) males and 27(58%) never smoker, 3(7%) light smoker and 16(35%) heavy smoker. The vast majority (93%,43/46) of pathological type was adenocarcinoma, other types including 1 squamous carcinoma and 2 with difficult histological classification. 42 were advanced stage at diagnosis, while 4 were early stage. The common metastasis sites was lung, pleural effusion, liver and adrenal gland. Retroperitoneal lymph node metastasis was also found frequently (17%,8/46). In the advanced and recurrent NSCLC with BRAF mutation, 25 patients had detailed treatment record and follow up information. Most (20/25) of them had chose chemotherapy ± bevacizumab as first line, while the rest accepted other treatment, including 1 chemotherapy combined with pembrolizumab, 3 Icotinib and 1 vandetanib. The Overall Response Rate (ORR) of first line was 44% (11/25) and median PFS was 8.67m(6.9m-10.5m). After disease progress, nearly half (11/25) of the patients accepted second line treatment, 3 had pembrolizumab, 3 enrolled in clinical trials, and others accepted chemotherapy or antiangiogenesis drugs. The ORR of second line was 14.3% (2/14) and median PFS was 5.1m(2.2m-8.0m). At the data cutoff of follow-up (July 31, 2020), OS events were 11 (44%), and median OS was 33.9m(3.2m-64.7m). Conclusion: The most common genotype of NSCLC with BRAF mutation was V600E mutation, which was more tendency to have a concomitant mutation, the therapeutic response was well, and overall survival data had showed a promising outcomes.