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Nearly half of lung large cell neuroendocrine carcinoma (LCNEC) patients are diagnosed at an advanced stage and face a high early death risk. Our objective was to develop models for assessing early death risk in stage IV LCNEC patients. We used surveillance, epidemiology, and end results (SEER) databases to gather data on patients with stage IV LCNEC to construct models and conduct internal validation. Additionally, we collected a dataset from the Second Affiliated Hospital of Nanchang University for external validation. We used the Pearson correlation coefficient and variance inflation factor to identify collinearity among variables. Logistic regression analysis and least absolute shrinkage and selection operator analysis were employed to identify important independent prognostic factors. Prediction nomograms and network-based probability calculators were developed. The accuracy of the nomograms was evaluated using receiver operating characteristic curves. The goodness of fit of the nomograms was evaluated using the Hosmer-Lemeshow test and calibration curves. The clinical value of the models was assessed through decision curve analysis. We enrolled 816 patients from the surveillance, epidemiology, and end results database and randomly assigned them to a training group and a validation group at a 7:3 ratio. In the training group, we identified 9 factors closely associated with early death and included them in the prediction nomograms. The overall early death model achieved an area under the curve of 0.850 for the training group and 0.780 for the validation group. Regarding the cancer-specific early death model, the area under the curve was 0.853 for the training group and 0.769 for the validation group. The calibration curve and Hosmer-Lemeshow test both demonstrated a high level of consistency for the constructed nomograms. Additionally, decision curve analysis further confirmed the substantial clinical utility of the nomograms. We developed a reliable nomogram to predict the early mortality risk in stage IV LCNEC patients that can be a helpful tool for health care professionals to identify high-risk patients and create personalized treatment plans., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of malignant pulmonary tumor. The incidence rate of LCNEC was reported to be 0.3%-3% in lung cancers. Although LCNEC is classified as non-small cell lung cancer (NSCLC), it is more aggressive and malignant than other NSCLC, and its biological behavior is similar to that of small cell lung cancer (SCLC). Most of the LCNEC patients are elderly smoking male and the clinical manifestations are not specific. The imaging manifestations of the tumors are often located in the periphery and the upper lobes, and the enlargement of mediastinal or hilar lymph nodes is common. The diagnosis is mainly based on pathology by the histological features and immunohistochemistry (IHC). Specific neuroendocrine markers such as chromogranin A (CgA), synaptophysin (Syn) and CD56 are usually diffusely positive in LCNEC, and found that insulinoma-associated protein (INSM1) and high rate of Ki-67 are helpful for diagnosis. More differential diagnoses also increase the difficulty of correctly diagnosing LCNEC. The rise of LCNEC molecular typing in recent years may be helpful for diagnosis and subsequent treatment. This review focuses on the epidemiological features, imaging studies, pathology, diagnosis, treatment, and prognosis of LCNEC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Fan and Lu.)

Aim: The aim of this study was to evaluate the frequency and median time for the development of metastases and prognosis by metastatic site after the diagnosis of non-small-cell lung cancer (NSCLC). Patients & methods: This cohort study was conducted with 1096 patients diagnosed with NSCLC between 2006 and 2014. Results: The most prevalent site of NSCLC metastases was the respiratory system. The nervous and adrenal systems presented the longest median time for the development of metastases. The 6-month survival varied from 68.2% for liver to 79.9% for the nervous system. Bone metastases were associated with a higher risk of death. Conclusion: The respiratory system was the most prevalent site of metastases. OS and risk of death varied according to the metastatic site.

Background: We assessed associations between metformin use and survival in a nationwide Norwegian cohort of lung cancer (LC) patients., Methods: The study linked 22,324 LC patients from the Cancer Registry of Norway diagnosed 2005-2014 with the Norwegian Prescription Database. We estimated associations of pre- and post-diagnostic metformin use with overall survival (OS) and LC-specific survival (LCSS) using multivariable time-fixed and time-dependent Cox regression., Results: Pre-diagnostic metformin use was not associated with improved survival in all patients. Nevertheless, pre-diagnostic metformin use was associated with better LCSS in squamous cell carcinoma (SCC) patients (hazard ratio (HR) = 0.79; 95% confidence interval (CI) 0.62-0.99) and in patients with regional stage SCC (HR = 0.67; 95%CI 0.47-0.95). Post-diagnostic metformin use was associated with improved LCSS in all patients (HR = 0.83; 95%CI 0.73-0.95), in patients with SCC (HR = 0.75; 95%CI 0.57-0.98), regional stage LC (HR = 0.74; 95%CI 0.59-0.94), and regional stage SCC (HR = 0.57; 95%CI 0.38-0.86). OS showed similar results. Analyses of cumulative use showed a dose-response relationship in all patients, patients with adenocarcinoma and SCC, and with regional and metastatic LC., Conclusions: Metformin use was associated with improved survival, especially LCSS in patients with regional stage SCC. Further prospective studies are required to clarify the role of metformin in LC treatment.

Background: Lung cancer is the most common cause of cancer-related death., Objectives: To identify changing patterns of lung cancer and its histologic subtypes among different population groups in Israel over a 25 year period., Methods: Primary lung cancers, all types and all stages, diagnosed during 1990-2014 were recorded in the Israel National Cancer Registry database. Demographic information was retrieved from the National Population Register. Age-standardized rates for the different subgroups were calculated for each year. Joinpoint software was used to analyze trends in incidence., Results: We identified 42,672 lung cancer cases. The most common histology was adenocarcinoma (34%), followed by squamous cell carcinoma (19%), large cell/not-otherwise-specified (19%), other histologies (15%), and small cell lung cancer (11%). The adenocarcinoma incidence rose from 25.7% to 48.2% during the examined period. Large cell/not-otherwise-specified incidence peaked around 2005-2006 and declined after. Lung cancer incidence increased significantly for the population overall and specifically in Arab females, followed by Jewish females and by Arab males. Adenocarcinoma and small cell lung cancer increased in Jewish females and in Arab males. A younger age of diagnosis was seen in Arab compared to Jewish patients., Conclusions: Jewish females and Arab males and females living in Israel demonstrated a constant increase in lung cancer incidence, mostly in adenocarcinoma and small cell lung cancer incidence. In addition, a younger age of diagnosis in Arabs was noted. Smoking reduction interventions and screening should be implemented in those populations.

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes. Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations. Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men. Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 μg/m 3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined. Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.

Background: Pulmonary large cell carcinoma (LCC) is an infrequent neoplasm with a poor prognosis. This study explored the clinical characteristics and survival prognostic factors of LCC patients., Methods: Patient data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Chi-square tests or rank-sum tests were used to compare differences in clinical characteristics. Log-rank tests, univariate, and multivariate analyses were performed to investigate the independent factors of survival. Analyses of stage I-IV patients were performed to further explore the optimal treatment., Results: In total, 3197 LCC patients were included in this analysis. Compared with other non-small cell lung cancers (NSCLCs), there was a worse overall survival (OS) from LCC. LCC was more common in males, over age 60 and in the upper lobe. A total of 73.6% of patients were stage III/IV. The median OS of stage I-IV patients was 42 months, 22 months, 11 months, and three months, respectively. The elderly, males, later stage, and main bronchus location, or overlapping lesions were risk factors for survival prognosis. In stage I-III patients, treatment including surgery could significantly reduce the risk of death by 60% at least compared with no therapy. Surgery was still beneficial for stage IV patients, and the hazard ratio (HR) compared with no therapy was 0.462 (P = 0.001)., Conclusions: Our study concluded that LCC has unique clinical features, and that age, sex, primary site, stage, and treatment are significantly related to OS. Surgery based comprehensive treatments are effective for LCC., Key Points: Significant findings of the study In stage IV patients, chemotherapy or radiotherapy combined with surgery could further improve survival. When surgical resection involved more than one lobe, it may be beneficial for survival prognosis. What this study adds LCC patients were principally male and over age 60, with later stages and poor survival prognosis. Age, sex, stage, primary site and therapy are closely related to survival., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Pulmonary large cell carcinoma (LCC) is a poorly differentiated and rare tumor with dismal outcome, and there are no recommended treatments for LCC. Little is known about the efficacy of postoperative chemotherapy in patients with early stage LCC., Methods: The patients with early stage I/II LCC in the Surveillance, Epidemiology and End Results (SEER) database between 2004 and 2015 were retrospectively reviewed. The overall survival (OS) of patients with LCC at different stages and treatments were evaluated by Kaplan-Meier analysis with log-rank test. Univariate and multivariate Cox proportional risk regression analysis were employed to determine the independent risk factors of OS. Finally, a nomogram was constructed to predict the 1 -, 3- and 5-year OS of early stage LCC patients., Results: A total of 1,099 pulmonary LCC cases were included in this study. 71.8% of patients were over 60 years old, and 66.7% of the tumor lesions located in the upper lobe, followed by the lower lobe (25.7%). Meanwhile, the majority of tumors showed poor differentiation (96.1%). The median OS of surgical patients with or without post-operative adjuvant chemotherapy was 61 and 47 months, respectively. Post-operative chemotherapy was associated with better OS (HR: 0.805; 95% CI: 0.676-0.959, P=0.020). For patients with tumor size >3 cm or IB stage tumor, the prognosis of postoperative chemotherapy was better than that of patients without chemotherapy. Multivariate Cox analysis revealed the age, stage and treatments were independent risk factors of OS for early stage LCC. The nomogram had a calibration index of 0.581., Conclusions: The incidence of LCC was high in the elderly, and it generally had poor differentiation. Post-operative chemotherapy is strongly recommended for patients with LCC at stage IB or higher.

Introduction: Large-cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung malignancies. There are limited data on the epidemiology and best treatment practices for this malignancy. This study aimed to be the largest cohort with the most up-to-date analysis of the epidemiology of LCNEC., Patients and Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify cases of LCNEC diagnosed from 2010 through 2015, reflecting years the American Joint Committee on Cancer 7th edition staging system was in use. Using these data, we compared the epidemiology, demographics, clinical characteristics, and survival times of LCNEC with small-cell lung carcinoma (SCLC) and non-SCLC (NSCLC). Trends in incidence and mortality were recorded from 2004 to 2015., Results: A total of 195,148 cases of lung cancer, including 1681 (0.9%) cases of LCNEC, were analyzed. LCNEC was more common among male subjects, and disease usually presented at stage IV (55%). Brain metastasis occurred more frequently in LCNEC (19.2%) than SCLC (16.7%, P < .001) or NSCLC (13%, P < .001). Incidence increased by 0.011 people per 100,000 per year, primarily of stage IV disease. Annual mortality from LCNEC doubled over the time period studied. Survival in patients with stage I-III LCNEC mirrored survival trends of patients with NSCLC, whereas stage IV LCNEC behaved similarly to SCLC., Conclusion: LCNEC generally presents at more advanced stages than NSCLC but earlier than SCLC. Stage I-III LCNEC behaves similarly to NSCLC, whereas stage IV is more akin to SCLC. LCNEC incidence is increasing. Despite this, it remains poorly studied and did not demonstrate an improved prognosis in our cohort., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Median age at diagnosis of lung cancer is 70 years. Its presentation in patients 40 or younger is uncommon and it has been proposed that maybe it is a different disease due to its clinical characteristics and genetic makeup. There are a limited number of studies in this population and they report different clinic-pathological characteristics in comparison with older patients., Methods: We described the incidence of lung cancer patients diagnosed at age 40 or younger at the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima-Peru; from 2009 to 2017 and evaluated the characteristic of NSCLC. Epidemiologic and clinic-pathological data was collected from clinical files. Analysis was carried out using SPSSvs19 software., Results: We identified 3823 patients with lung cancer seen at INEN during the study period. Among these, 166 (4.3%) patients were 40 years or younger, and 137/166 (82.5%) were NSCLC. Median age at diagnosis was 36 years (range 14-40 years) and 59.1% of patients were female. A smoking history was present in 14.4% of patients. Frequent symptoms at diagnosis were cough (62.0%), chest pain (51.8%) and dyspnea (40.9%). Adenocarcinoma was the most common histological type (63.3%). Most patients had advanced disease at diagnosis (84.7%). The median overall survival was 8.2 months., Conclusions: The proportion of young patients with lung cancer in our population is higher than that reported in the most recent literature. Lung cancer in the young is mostly sporadic, more frequent in women, usually adenocarcinoma type and it presents with advanced disease, resulting in a very poor survival.

Objective: The objective was to describe the prevalence of baseline comorbidities in patients with advanced NSCLC and the incidence rate of relevant outcomes commonly associated with NSCLC, and its treatments, in the year after diagnosis., Methods: A non-interventional cohort study compared adult patients newly diagnosed with advanced NSCLC during 2006-2013 with the general population. The prevalence of comorbidities one year before and incidence of relevant outcomes one year after NSCLC diagnosis were informed by data on all healthcare visits from two large regional registers. Main summary measures were prevalence, median survival, odds ratios (ORs), incidence rate (IR) and mortality rate (MR) with corresponding 95% confidence intervals (CIs)., Results: A total of 3,834 NSCLC patients were matched to 15,332 comparators. The prevalence of analysed comorbidities was significantly higher for NSCLC patients compared to the general population, with an OR of 2.44 (95% CI 2.27-2.63). Overall, the majority of IRs were higher for NSCLC patients, compared to the general population. The all-cause MR for the NSCLC cohort was significantly higher leading to an IR ratio of 32.5 (95% CI 31.0-34.2)., Conclusions: Advanced NSCLC patients presented with significantly more comorbidities in the year before diagnosis and relevant outcomes of interest in the year after., (© 2019 John Wiley & Sons Ltd.)

Introduction: The National Lung Screening Trial (NLST) randomized high-risk current and former smokers to three annual screens with either low-dose computed tomography (LDCT) or chest radiography (CXR) and demonstrated a significant reduction in lung cancer mortality in the LDCT arm after a median of 6.5 years' follow-up. We report on extended follow-up of NLST subjects., Methods: Subjects were followed by linkage to state cancer registries and the National Death Index. The number needed to screen (NNS) to prevent one lung cancer death was computed as the reciprocal of the difference in the proportion of patients dying of lung cancer across arms. Lung cancer mortality rate ratios (RRs) were computed overall and adjusted for dilution effect, with the latter including only deaths with a corresponding diagnosis close enough to the end of protocol screening., Results: The median follow-up times were 11.3 years for incidence and 12.3 years for mortality. In all, 1701 and 1681 lung cancers were diagnosed in the LDCT and CXR arms, respectively (RR = 1.01, 95% confidence interval [CI]: 0.95-1.09). The observed numbers of lung cancer deaths were 1147 (with LDCT) versus 1236 (with CXR) (RR = 0.92, 95% CI: 0.85-1.00). The difference in the number of patients dying of lung cancer (per 1000) across arms was 3.3, translating into an NNS of 303, which is similar to the original NNS estimate of around 320. The dilution-adjusted lung cancer mortality RR was 0.89 (95% CI: 0.80-0.997). With regard to overall mortality, there were 5253 (with LDCT) and 5366 (with CXR) deaths, for a difference across arms (per 1000) of 4.2 (95% CI: -2.6 to 10.9)., Conclusion: Extended follow-up of the NLST showed an NNS similar to that of the original analysis. There was no overall increase in lung cancer incidence in the LDCT arm versus in the CXR arm., (Published by Elsevier Inc.)

Background: Bronchopulmonary neuroendocrine tumours are divided into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung cancer (SCLC)., Aim: To thoroughly describe a cohort of 252 patients with TC, AC and LCNEC (SCLC excluded)., Material and Methods: Collection of data from 252 patients referred to and treated at Rigshospitalet 2008-2016. Data was collected from electronic patient files and our prospective NET database. Statistics were performed in SPSS., Results: 162 (64%) had TC, 29 (12%) had AC and 61 (24%) had LCNEC. Median age at diagnosis was 69 years (range: 19-89) with no difference between genders. Thoraco-abdominal CT was performed in all patients at diagnosis. FDG-PET/CT was performed in 207 (82%) at diagnosis and was positive in 95% of the entire cohort, with no difference between tumour types. Synaptophysin was positive in 98%, chromogranin A in 92% and CD56 in 97%. Mean Ki67 index was 5% in TC, 16% in AC and 69% in LCNEC (p < 0.001). Metastatic disease was found in 4% of TC, 27% of AC and 58% of LCNEC at time of initial diagnosis (p < 0.001). In total 179 patients (71%) underwent surgical resection; TC: 87%, AC: 72% and LCNEC: 28% (p < 0.001). Of the resected patients, 11 (6%) had recurrence. Five-year survival rate was 88% for TC, 63% for AC and 20% for LCNEC., Conclusion: In this comprehensive study of a cohort of 252 patients, one of the largest until date, with TC, AC and LCNEC, the gender distribution showed female predominance with 68%. FDG-PET/CT was positive in 95% of the patients independent of tumour type, which confirms that FDG-PET/CT should be a part of the preoperative work-up for TC, AC and LCNEC. Tumour type was the single most potent independent prognostic factor., (Copyright © 2019 Elsevier B.V. All rights reserved.)

BACKGROUND The aim of this study was to assess the incidence, clinicopathologic characteristics, prognostic factors, and treatment outcomes in lung large cell neuroendocrine carcinoma (LCNEC). MATERIAL AND METHODS Patients diagnosed with lung LCNEC between 2000 and 2013 were identified using the Surveillance, Epidemiology, and End-Results database. Kaplan-Meier methods and univariate and multivariate analyses were used for statistical analysis. RESULTS A total of 2097 patients were identified. The total age-adjusted incidence rate of lung LCNEC was 0.3/100 000, with a rise in incidence over the study period. The 5-year lung cancer-specific survival (LCSS) and overall survival (OS) were 20.7% and 16.7%, respectively. Multivariate analysis indicated that age ³65 years, male sex, advanced tumor stage, advanced nodal stage, not undergoing surgery. and not undergoing chemotherapy were independent adverse indicators for survival outcomes. After stratification by tumor stage, undergoing surgery was associated with more favorable LCSS and OS compared with those without surgery, regardless of tumor stage. CONCLUSIONS LCNEC is a rare lung cancer subtype with a dismal prognosis. Primary surgical treatment has significant survival benefits, even for stage IV patients. The optimal treatment strategies for lung LCNEC require further investigation.

Background: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare tumor with high mutational burden. Two subtypes of LCNEC are recognized, the co-mutated TP53 and RB1 group and the TP53 and STK11/KEAP1 group. We investigated PD-L1 and CD8 expression in a well characterized stage IV LCNEC cohort and compared expression in the two subtypes., Methods: Immunohistochemical (IHC) analysis for PD-L1 and CD8 was performed on pathological reviewed pretreatment tumor samples for 148 stage IV LCNEC. Data about targeted next generation sequencing (TNGS) (TP53, RB1, STK11, KEAP1) and IHC for RB1 were available for most tumors. IHC staining for PD-L1 (DAKO 28-8) was performed and scored positive if tumors showed ≥1% membranous staining. CD8 was scored for intra-tumor T-cells and stromal cells., Results: PD-L1 IHC expression data could be generated in 98/148 confirmed LCNEC samples along with RB1 IHC (n = 97) of which 77 passed quality control for TNGS. PD-L1 expression was positive in 16/98 cases (16%); 5 (5%) with ≥50%. PD-L1 expression was equal in RB1 mutated and RB1 wildtype tumors. None of STK11 mutated tumors (n = 7) expressed PD-L1. PD-L1 expression was correlated with superior overall survival (OS), hazard ratio 0.55 ((95% Confidence Interval 0.31-0.96), p = 0.038). Intra-tumor CD8 was associated with PD-L1 expression (p = 0.021) and stromal and intra-tumor CD8 were correlated with improved OS (p = 0.037 and p = 0.026 respectively)., Conclusions: PD-L1 expression was positive in 16% of stage IV LCNEC tumors. This was independent of molecular subtype but associated with CD8 expression. In LCNEC patients with PD-L1 and/or CD8 expression superior OS was observed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The purpose of the present study was to characterize the prevalence, associated factors, and to construct a nomogram for predicting bone metastasis (BM) with different histological types of lung cancer., Patients and Methods: This study was a descriptive study that basing on the invasive lung cancer patients diagnosed between 2010 and 2014 in Surveillance, Epidemiology, and End Results program. A total of 125,652 adult patients were retrieved. Logistic regression analysis was conducted to investigate homogeneous and heterogeneous factors for BM occurrence. Nomogram was constructed to predict the risk for developing BM and the performance was evaluated by the receiver operating characteristics curve (ROC) and the calibration curve. The overall survival of the patients with BM was analyzed using the Kaplan-Meier method and the survival differences were tested by the log-rank test., Results: A total of 25,645 (20.9%) were reported to have BM, and the prevalence in adenocarcinoma, squamous cell carcinoma, small cell lung cancer (SCLC), large cell lung cancer (LCLC), and non-small cell lung cancer/not otherwise specified lung cancer (NSCLC/NOS) were 24.4, 12.5, 24.7, 19.5 and 19.4%, respectively, with significant difference (P < 0.001). Male gender, more metastatic sites and lymphatic metastasis were positively associated with BM in all lung cancer subtypes. Larger tumor size was positively associated with BM in all the lung cancer subtypes except for NSCLC/NOS. Poorly differentiated histology was positively associated with adenocarcinoma, squamous cell carcinoma and NSCLC/NOS. The calibration curve and ROC curve exhibited good performance for predicting BM. The median survival of the bone metastatic lung cancer patients was 4.00 (95%CI: 3.89-4.11) months. With the increased number of the other metastatic sites (brain, lung and liver metastasis), the survival significantly decreased (p < 0.001)., Conclusion: Different lung cancer histological subtypes exhibited distinct prevalence and homogeneity and heterogeneity associated factors for BM. The nomogram has good calibration and discrimination for predicting BM of lung cancer.

Introduction: The incidence of lung cancer among never-smokers has been increasing rapidly. The U. S. National Lung Screening Trial and the NELSON trial showed that screening using low-dose computerized tomography (LDCT) effectively reduced lung cancer mortality among heavy smokers. However, its effectiveness in never-smokers has not been well investigated. This study investigated the role of LDCT in lung cancer screening among never-smokers., Methods: The study was designed as a single-center, retrospective cohort study. We analyzed the data on patients who underwent LDCT screening between May 2003 and June 2016. Nodules detected by computerized tomography were classified according to the Lung Imaging Reporting and Data System criteria. The detection rate and lung cancer outcomes (type of cancer, staging of lung cancer, and mortality) according to smoking history were determined., Results: Of the 28,807 enrolled patients, 12,176 were never-smokers; of these patients, 7744 (63.6%) were women and 1218 (10.0%) were found to have lung nodules. Overall, lung cancer was diagnosed in 55 never-smokers (0.45%). In contrast, lung cancer was diagnosed in 143 (0.86%) of the 16,631 ever-smokers. Of the never-smokers with lung cancer, 51 (92.7%) presented with stage I disease, and all patients had adenocarcinomas., Conclusions: In the never-smoker population, LDCT screening helped to detect a significant number of lung cancers. Most of these lung cancers were detected at a very early stage. The positive results of the National Lung Screening Trial in the United States and the NELSON trial may have established the value of LDCT screening for heavy smokers, but future research should consider the value of using LDCT screening in the never-smoker population., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

The WORLD07 study was a female-specific database, to prospectively characterise the clinical, histological, molecular and treatment-related features in Spanish women with lung cancer. Data were collected from patients' medical records and patient interviews from October 2007 to December 2012. A total of 2,060 women were analysed: median age, 61.3 years; white, 98.6%; postmenopausal, 80.2%; and no smokers, 55% including never smokers and ex-smokers. A family history of cancer was found in 42.5% of patients, 12.0% of patients had had a previous history of cancer (breast cancer, 39.7%). Most patients (85.8%) were diagnosed of non-small-cell lung cancer (NSCLC), most commonly reported with adenocarcinoma (71.4%), which was stage IV at diagnosis in 57.6%. Median overall survival (OS) for the entire population was 24.0 months, with a 1- and 2-year survival rate of 70.7% and 50.0% respectively. Median OS in patients with small-cell lung cancer was 18.8 months versus 25.0 months in patients with NSCLC (p = 0.011). Lung cancer appears to be a biologically different disease in women. By collecting prospective information about characteristics of women with lung cancer attending university hospitals in Spain, we hope to highlight the need to develop strategies based on gender differences and influence future healthcare policy., (© 2018 John Wiley & Sons Ltd.)

Background: The present study examined clinical stage I non-small-cell lung cancer (NSCLC) treatment in the population-based California Cancer Registry., Patients and Methods: The characteristics associated with first clinical stage I NSCLC treatment (surgery, radiation, no local therapy) from 2003 to 2014 were identified using logistic regression. Survival was evaluated using Kaplan-Meier and Cox proportional hazard analyses., Results: Surgery was used in most patients who met the inclusion criteria (14,545 of 19,893; 73.1%), although relatively similar numbers had undergone radiation (n = 2848; 14.3%) or not received therapy (n = 2500; 12.6%). Surgery use ranged from 68.5% to 77.2% patients annually. The percentage of patients with no therapy decreased from 18.1% (315 of 1737) in 2003 to 10.3% (176 of 1703) in 2014, and radiation use increased from 10.7% (185 of 1737) in 2003 to 21.2% (361 of 1703) in 2014. Patients who did not receive therapy were more likely to be older, not white, male, and unmarried, to have no insurance or public insurance other than Medicare, to live in a lower socioeconomic status neighborhood, to have been seen at a non-National Cancer Institute cancer center hospital or hospital serving lower socioeconomic status patients, and to have larger tumors. The 5-year all-cause survival after no therapy (12.7%) was significantly worse than that after surgery (64.9%) or radiation (21.5%; P < .0001)., Conclusion: In the present population-based analysis, surgery was the most common treatment for clinical stage I NSCLC but was not used for almost 27% of patients. Radiation use increased and the proportion of patients who did not receive any therapy decreased over time., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Advanced stage non-small cell lung cancer (NSCLC) is a heterogenous disease, yet, with the exception of targeted therapies, most guidelines recommended uniform treatment irrespective of tumor burden or sites of metastases and this may explain, in part, the wide range of responses to same lines of therapy. Aim of work: In this work we tried to explore the effect of metastatic sites in on overall survival (OS), in an unselected group of Non-small cell lung cancer patients who received different treatments line. Methods: A retrospective analysis was performed on patients with stage IV NSCLC who received systemic treatment at UAB Cancer Center (NCI designated comprehensive cancer center) between 2002 to 2012. The details of sites of metastases, systemic therapy and overall survival were recorded for each patient. Result: In 409 patients who received systemic treatment, there was statistically significant lower OS in those presenting with liver metastases (p<0.001), adrenal metastases (p=0.011) and metastases to abdominal lymph nodes (p=0.014). There was no statistically significance difference in OS in patient presenting with pleural metastases or effusion (p=0.908), metastases to heart or pericardium (p=0.654), metastases to bone (p=0.281), brain (p=0.717) or skin and subcutaneous tissue (p=0.642). Conclusion: Intra-abdominal metastases confer a particularly poor prognosis in stage IV NSCLC treated with systemic therapy and may identify patients in whom aggressive treatment beyond first line therapy is not appropriate., (Creative Commons Attribution License)

Lung neuroendocrine tumors comprise 20% of all pulmonary tumors. Their appearance and behavior are very heterogeneous. Histologically they are divided into four groups, well-differentiated and low-malignant typical carcinoid, poorly differentiated and worse prognosis atypical carcinoid, and highly malignant small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma. Of these, the most common is small cell lung cancer with an incidence of 15%, while those of large cell neuroendocrine tumors and lung carcinoids are 3% and 2%, respectively. The treatment and prognosis of carcinoids are very different from those of highly malignant small cell and large cell neuroendocrine carcinomas. The paper summarizes the characteristics of lung neuroendocrine tumors.

Purpose: The purpose of this study is to assess temporal trends in population-based treatment and survival rates in patients with early-stage non-small cell lung cancer (NSCLC)., Methods: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Chi-square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 23.0., Results: Fifty-seven thousand and eighty-eight NSCLC patients with early-stage disease from 1988 to 2014 were identified. 6409 (11.2%) were diagnosed in 1988-1994, 5800 (10.2%) 1995-1999, 13,031 (22.8%) 2000-2004, 15,786 (27.7%) 2005-2009, and 16,062 (28.1%) 2010-2014. We observed a significant increase in the proportion of older patients, adenocarcinoma histology, and rate of wedge resection over the study period. The five-year overall survival (OS) for the entire cohort was 63.3%. Those undergoing resection without adjuvant therapy had the highest outcomes. Lobectomy was associated with better outcomes compared to wedge resection or pneumonectomy. A significant difference in five-year OS by year of diagnosis (1988-1994: 58.8% vs. 1995-1999: 60.6% vs. 2000-2004: 63.2% vs. 2005-2009: 66.1%; p < 0.001) was observed. This significant OS difference was also observed regardless of age, surgery type, and T stage, but also only in those with adenocarcinoma. On multivariable analysis, year of diagnosis, age, gender, race, treatment and surgery type, histology, T stage, and tumor grade remained independent prognostic factors for OS., Conclusions: Overall survival for early-stage NSCLC has significantly improved over the recent decades despite an increasing proportion of older patients and those undergoing sublobar resection or SBRT. This finding may be limited to those with adenocarcinoma.

Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3)., Patients and Methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables., Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology., Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.

Background: Overdiagnosis among clinically detected lung cancers likely consists of cases that are non-aggressive and slowly progressive and will never disseminate, cause symptoms or be a threat to a subject's survival, even if untreated. In this study, we estimate the prevalence of non-aggressive lung cancers from a large, population-based cancer registry., Methods: We identified individuals ≥65 years with histologically confirmed, untreated stage I non-small cell lung cancers (NSCLCs) from the Surveillance, Epidemiology, and End Results-Medicare registry. We estimated the rate of non-aggressive lung cancers by determining the point at which the cumulative lung cancer-specific survival curve no longer changed (ie, the slope approaches zero). At this point, there are no additional deaths due to progressive lung cancer observed among untreated patients after adjusting for deaths from competing risks (these long-term survivors can be considered 'non-aggressive cases)., Results: The overall rate of non-aggressive cancers among 2197 clinically detected cases of untreated stage I NSCLC was 2.4%, 95% CI: 1.0% to 3.8%. The rate of non-aggressive cancer was 1.9% (95% CI: 0.0% to 4.9%) for women and 2.4% (95% CI: 0.7% to 4.1%) for men (p=0.84). When stratifying by tumour size, non-aggressive cancer rates were 10.2% (95% CI: 0.0% to 29.3%), 2.1% (95% CI: 0.0% to 9.2%), 4.9% (95% CI: 0.0% to 10.3%), 1.8% (95% CI: 0.0% to 5.2%) and 0.0% (95% CI: 0.0% to 1.0%) for tumour sizes <15 mm, 15-24 mm, 25-34 mm, 35-44 mm and ≥45 mm, respectively. In comparison with the smallest tumour sizes (<15 mm), the rates of non-aggressive cancers were not statistically significantly different for tumour sizes 15-24 mm (p=0.36), 25-34 mm (p=0.57), 35-44 mm (p=0.38) and tumour sizes >45 mm (p=0.30)., Discussion: We found relatively low rates of non-aggressive cancers among clinically detected, stage I NSCLC regardless of sex or size. Our findings suggest that most clinically diagnosed early stage cancers should be treated with curative intent., Competing Interests: Competing interests: JPW is a member of the research board of EHE International, has received consulting honorarium from Quintiles, AstraZeneca and Merck and a research grant from Aventis Pharmaceutical and Quorum. KS has received honorarium from Gilead., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: To investigate the association of lung cancer with occupational exposure to textile dust and specifically to cotton dust in the population-based case-control study ICARE., Methods: Lifelong occupational history of 2926 cases and 3555 controls was collected using standardized questionnaires, with specific questions for textile dust exposure. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using unconditional logistic regression models controlling for confounding factors including smoking and asbestos exposure., Results: An inverse association between textile dust exposure and lung cancer was found among workers exposed ≥5% of their work time (OR = 0.80, 95%CI = 0.58-1.09), more pronounced for distant exposures (40+ years; up to a 56% reduced risk, statistically significant). The OR of lung cancer was significantly decreased among workers exposed to cotton fibers (OR = 0.70, 95%CI = 0.48-0.97)., Conclusions: Our results provide some evidence of a decreased risk of lung cancer associated with exposure to textile dust, particularly cotton., (© 2017 Wiley Periodicals, Inc.)

Background: Lung cancer can be described by histological subtype, of which small cell, squamous cell and adenocarcinoma are the most common. International data show that adenocarcinoma is becoming the dominant histological subtype of lung cancer although the relative risk due to smoking has been found to be smaller than that for other histological subtypes., Objective: The aim of the analysis was to describe the time trends in incidence of lung cancer among women and men in Germany according to histological subtype., Materials and Methods: All lung cancer cases (ICD-10 C33-C34) newly diagnosed between 2003 and 2012 and collected by the epidemiologic cancer registries of the German federal states with average completeness of registration of at least 90% were considered and grouped into histologic subtypes. If data on tumor histology were not microscopically verified or unspecific, multiple imputation techniques were applied to estimate the histologic subtype., Results: Among women age-standardized lung cancer rates increased considerably between 2003 and 2012 (annual percent change APC = 2.7%), mostly driven by a rising adenocarcinoma incidence (APC = 4.7%). Among men overall lung cancer rates decreased during the same time (APC = -1.7%). Still, a slight increase in adenocarcinoma incidence was also observed in men (APC = 1.0%)., Conclusion: The rising incidence of adenocarcinoma of the lung is alarming. The cancer registry data do not allow risk factor analysis. In the international discussion, the introduction of filter cigarettes as well as the changing composition of cigarettes has been hypothesized as being responsible. Further epidemiologic studies are strongly needed.

Background: Lung cancer is the fourth most common cancer in the Gulf Cooperation Council countries among males and the third among females. It is the commonest cancer among Bahraini males accounting for 16.9% of all cancers and the third in Bahraini females contributing to 5.8 % of all female cancers. The aim of this study was to describe the epidemiology of lung cancer among the Bahraini population during the period 1998-2011., Methods: All Bahraini registered lung cancer cases in the national cancer registry from 1 January 1998 to 31 December 2011 were included in the study. Incidence rates were calculated using the CANREG software, in which the annual crude incidence rates, age specific incidence rates and the age standardized incidence rate (ASR) were computed., Results: Six hundred sixty-four lung cancer cases (72.4%, males and 27.6% females) were diagnosed during the study period. The annual average number of cases was 47.5 per year. The mean age at diagnosis during the study period was 68.7±11.7 years. The average annual ASR was 26.1/100,000 among males and 10.0/100,000 among females. There was a tendency for a decreased trend of the ASR during 1998-2011 in both sexes. Twenty-six percent of lung cancer cases were squamous cell carcinoma and 17.9% adenocarcinoma. The grades of 70.3% were unknown and 13.4% were poorly differentiated. The stage was unknown for 65.0% of the cases, while 18.5% had distant metastasis and 9.8% were localized. The majority (88.9 %) of the lung cancer cases were dead by the end of the study period with a five-year survival rate of 3.0%., Conclusion: A welcomed decline in the incidence of lung cancer has been noted over the past 14 years. However, more efforts should be put to reduce the proportion of lung cancer cases with unknown stage and grade. The incidence of histological types, which are strongly dependent on tobacco smoking, notably small cell, squamous cell and large cell carcinomas, accounted for over one third of lung cancer cases. Future research should be directed towards better understanding of the lung cancer risk factors and the effectiveness of tobacco control measures in in the country.

We investigated occupational exposure to diesel motor exhaust (DME) and the risk of lung cancer by histological subtype among men, using elemental carbon (EC) as a marker of DME exposure. 993 cases and 2359 controls frequency-matched on age and year of study inclusion were analyzed by unconditional logistic regression in this Swedish case-control study. Work and smoking histories were collected by a questionnaire and telephone interviews. DME was assessed by a job-exposure matrix. We adjusted for age, year of study inclusion, smoking, occupational exposure to asbestos and combustion products (other than motor exhaust), residential exposure to radon and exposure to air pollution from road traffic. The OR for lung cancer for ever vs. never exposure to DME was 1.15 (95% CI 0.94-1.41). The risk was higher for squamous and large cell, anaplastic or mixed cell carcinoma than for alveolar cell cancer, adenocarcinoma and small cell carcinoma. The OR in the highest quartile of exposure duration (≥34 years) vs. never exposed was 1.66 (95% CI 1.08-2.56; p for trend over all quartiles: 0.027) for lung cancer overall, 1.73 (95% CI 1.00-3.00; p: 0.040) for squamous cell carcinoma and 2.89 (95% CI 1.37-6.11; p: 0.005) for the group of undifferentiated, large cell, anaplastic and mixed cell carcinomas. We found no convincing association between exposure intensity and lung cancer risk. Long-term DME exposure was associated with an increased risk of lung cancer, particularly to squamous cell carcinoma and the group of undifferentiated, large cell, anaplastic or mixed carcinomas.

Objectives: Large-cell neuroendocrine carcinoma (LCNC) is a rare tumour characterized by aggressive biological behaviour and poor prognosis. Due to its rarity and the lack of randomized clinical trials, the best treatment is still under debate. Some recent reports indicate that adjuvant chemotherapy (CT) may have a beneficial effect on survival. Our goal was to evaluate this finding using a large series of patients with neuroendocrine tumours obtained from the European Society of Thoracic Surgeons database., Methods: Data for 400 patients with LCNC operated on in 14 thoracic surgery institutions worldwide between 1992 and 2014 were collected retrospectively. Overall survival was the primary endpoint; we used a multivariable Cox regression model to evaluate which clinical variables may influence patient outcomes; we also focused on the possible prognostic role of adjuvant CT. A propensity score (PS) analysis using the inverse probability of treatment weighting was also carried out., Results: The 3- and 5-year survival rates were 54.1% and 45%, respectively. With the multivariable model, we found that increasing age, Eastern Cooperative Oncology Group Performance Status ≥2 and advanced TNM stage were indicators of poor prognosis. Weak evidence of a higher overall survival in patients receiving adjuvant CT (adjusted hazard ratio 0.73; 95% confidence interval: 0.56-0.96, P  = 0.022) was observed., Conclusions: A trend towards benefit from adjuvant CT has been observed in patients with LCNC. Although surgical procedures remain the mainstay of curative options, combination with other treatments (e.g. neoadjuvant CT/radiotherapy) should be evaluated by future studies., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Coexisting disease constitutes a challenge for the provision of optimal cancer care. The influence of comorbidity on lung cancer management and prognosis remains incompletely understood. We assessed the influence of comorbidity on treatment intensity and prognosis in a population-based setting in patients with nonsmall cell lung cancer., Material and Methods: Our study was based on information available in Lung Cancer Data Base Sweden (LcBaSe), a database generated by record linkage between the National Lung Cancer Register (NLCR) and several other population-based registers in Sweden. The NLCR includes data on clinical characteristics on 95% of all patients with lung cancer in Sweden since 2002. Comorbidity was assessed using the Charlson Comorbidity Index. Logistic regression and time to event analysis was used to address the association between comorbidity and treatment and prognosis., Results: In adjusted analyses encompassing 19,587 patients with a NSCLC diagnosis and WHO Performance Status 0-2 between 2002 and 2011, those with stage-IA-IIB disease and severe comorbidity were less likely to be offered surgery (OR: 0.45; 95% CI: 0.36-0.57). In late-stage disease (IIIB-IV), severe comorbidity was also associated with lower chemotherapy treatment intensity (OR: 0.76; 95% CI: 0.65-0.89). In patients with early, but not late-stage disease, severe comorbidity in adjusted analyses was associated with an increased all-cause mortality, while lung cancer-specific mortality was largely unaffected by comorbidity burden., Conclusions: Comorbidity contributes to the poor prognosis in NSCLC patients. Routinely published lung cancer survival statistics not considering coexisting disease conveys a too pessimistic picture of prognosis. Optimized management of comorbid conditions pre- and post-NSCLC-specific treatment is likely to improve outcomes.

Background: Thoracoscopic lobectomy for primary lung cancer has become increasingly popular worldwide due to several advantages over open lobectomy including reduced pain, reduced length of hospital stay, and comparable oncologic outcomes. The costs of thoracoscopic versus conventional open lobectomy have been compared in several studies with variable results. We compared the costs of thoracoscopic versus open lobectomy in lung cancer patients in Taiwan., Methods: Patients who underwent lobectomy for primary lung cancer from the Taiwan National Health Insurance Research Database (NHIRD) between 2004 and 2010 were identified. Patient characteristics, operative data, and costs for each part of the hospitalization for surgery and 30 days of care after discharge were analyzed., Results: A total of 5366 patients with complete clinical data who underwent either conventional open lobectomy (n = 3166, 59 %) or thoracoscopic lobectomy (n = 2200, 41 %) for primary lung cancer were identified from the database. Compared with open lobectomy, thoracoscopic lobectomy was associated with younger age, less comorbidity, shorter anesthesia times, and reduced lengths of hospital stay. Total hospital costs, operative costs, and other costs were significantly higher in the thoracoscopic group. The 30-day after discharge costs were significantly lower in the thoracoscopic group., Conclusions: Thoracoscopic lobectomy for primary lung cancer in Taiwan was associated with higher total hospital costs but lower 30 days after discharge costs than open lobectomy. These differences may have resulted from higher operative and instrument costs in the thoracoscopic group.

Purpose: To analyze and interpret age- and sex-specific incidence trends of lung cancer in Granada over the period 1985-2012 and to further analyze these trends by histologic subtype., Methods: Incidence data were obtained from the population-based cancer registry located in Granada (Southern Spain). All cases with newly diagnosed primary lung cancer over the period 1985-2012 (n = 8658) and defined by International Classification of Diseases 10th Revision (codes C33-C34) were included. Joinpoint regression analysis of age-standardized incidence rates was used to estimate the annual percent change (APC) and 95% confidence intervals. Results are presented overall and by sex, age groups (0-34, 35-54, 55-64, 65-74, ≥75 years) and histologic subtypes., Results: Temporal trends of incidence rates by sex, over the period 1985-2012, showed a distinct pattern. A significant change point of the trend was observed in males in 1994 (APC: +2.5%; 95% CI 0.7-4.4 from 1985 to 1994 and -1.4%; 95% CI -2.0 to -0.7 from 1994 onward). This general change was mainly caused by the age group 65-74 years and by the higher incidence of squamous cell carcinoma histologic subtype. In females, lung cancer incidence increased over the entire study period by +4.2% per year (95% CI 3.1-5.4); this trend was mainly caused by the age group 55-64 years (APC = +7%) and by adenocarcinoma incidence between women (APC = +6.8%)., Conclusion: Male lung cancer incidence rates have decreased in Granada, while female rates have increased overall especially in younger women. These trends may reflect the increased consumption of cigarettes in women, especially during younger ages. Lung cancer prevention through tobacco control policies are therefore of utmost importance.

Background: Neuroendocrine tumors represent 20% of primary lung neoplasms in some registries. According to the WHO classification of 2004, reconsidered for 2015, these lung tumors are divided into 4 groups: typical and atypical carcinoid, small cell and large cell neuroendocrine carcinomas. We report in this paper, for the first time in Lebanon, the distribution and the population characteristics of these tumors., Materials and Methods: This descriptive retrospective study concerned all the pulmonary neuroendocrine tumors (NET) with their characteristics diagnosed in Hotel Dieu de France in Beirut, Lebanon from 2001 to 2012, with attention to features like age, gender and subgroup., Results: Of 194 patients with pulmonary NET, 12.4% were typical carcinoid tumors, 3.6% atypical carcinoid, 66.5% small cell lung cancer, 7.7% combined small cell carcinomas and 9.8% large cell neuroendocrine tumors. The mean ages of patients were respectively 51.2 years in typical carcinoid, 64 years in atypical carcinoid, 64.2 years in small cell lung cancers, 67.2 in combined small cell lung cancer and 66.9 in large cells neuroendocrine tumors. The M/F sex ratios were respectively 0.3, 1.3, 1.4, 2.7 and 2.2., Conclusions: The characteristics of lung neuroendocrine tumors in our Lebanese institution are comparable to those reported in the literature.

Somatic mutations of EGFR and KRAS gene represent the most common alterations currently known in NSCLC patients. This study explored the frequency, distribution pattern of EGFR and KRAS mutations in Indian patients. The frequencies of EGFR and KRAS mutations were 29 % (116/400) and 4.5 % (6/132) respectively. Both EGFR and KRAS mutations were prevalent in females, and a trend towards higher mutation frequency was seen in patients under ≥ 60 years age. The presence of EGFR and KRAS mutations were higher in adenocarcinomas in comparison to other histological subtype. Sequencing analysis of EGFR exon 18 revealed Inframe deletion (G709&#95;T710 > A) and missense mutation (K713R). Among exon 19 positive cases, 49.3 % (37/75) were in-frame deletions, of which E746&#95;A750del was frequent. Similarly, ~47 % (35/75) cases showed complex mutation involving indel. Among mutations in exon 20 (N = 9), 8 were substitutions, one showed duplication, while all exon 21 mutations were of the missense types with L858R as the most recurrent type. Sequencing analysis of KRAS exon 1 revealed three different types codon 12 substitutions resulting in c34G > T (G12C) (n = 4), c.35G > A (G12D) (n = 1), and c.35G > T (G12V) (n = 1). In conclusion, the present study is an example of molecular diversity of EGFR and KRAS gene in Indian patients and further confirms that the frequency of EGFR and KRAS mutations varies considerably globally. To the best of our knowledge, this is the first Indian study to evaluate KRAS mutation. The current study also served to identify novel variations that added new insights into the genetic heterogeneity of NSCLC.

Introduction: Oncological treatment of lung cancer has been available in Greenland since 2004. We evaluated patient characteristics and survival rates for the first six years of local lung cancer treatment., Methods: From September 2004 to August 2010, a total of 173 patients with lung cancer were referred to treatment at Queen Ingrid's Hospital. On 1 February 2014, treatment results, survival, and prognostic variables were analysed., Results: The mean age at diagnosis was 63 years. Non-small cell lung cancer (NSCLC) was diagnosed in 145 patients (84%); 56% had squamous cell carcinoma, 34% had adenocarcinoma, 2% had large cell carcinoma and 8% had NSCLC not otherwise specified (NOS). In all, 28 (16%) had small cell lung cancer. A total of 142 patients (82%) received treatment; 20 underwent surgery (ten stage Ib, one stage IIa, five stage IIb, four stage IIIa); palliative chemotherapy was given to 122 of the 142 treated patients (86%). Of these, 36 patients (30%) received second-line chemotherapy.The median survival of patients undergoing primary lobectomy/pneumonectomy, palliative chemotherapy, and no treatment was 76.3 months, 11.8 months, and 2.0 months, respectively (p < 0.0001)., Conclusion: Evaluation of the first six years of lung cancer treatment in Greenland revealed a disease incidence and survival comparable to those found in the Nordic countries. To further decrease mortality from lung cancer, health-care resources should continue to be allocated to the prevention and treatment of lung cancer in Greenland., Funding: not relevant., Trial Registration: not relevant.

Background: Lung cancer (LC) incidence in the United States (US) continues to decrease but with significant differences by histology, gender and race. Whereas squamous, large and small cell carcinoma rates have been decreasing since the mid-80s, adenocarcinoma rates remain stable in males and continue to increase in females, with large racial disparities. We analyzed LC incidence trends by histology in the US with an emphasis on gender and racial differences., Methods: LC incidence rates from 1973-2010 were obtained from the SEER cancer registry. Age-adjusted incidence trends of five major histological types by gender and race were evaluated using joinpoint regression. Trends of LC histology and stage distributions from 2005-2010 were analyzed., Results: US LC incidence varies by histology. Squamous, large and small cell carcinoma rates continue to decrease for all gender/race combinations, whereas adenocarcinoma rates remain relatively constant in males and increasing in females. An apparent recent increase in the incidence of squamous cell carcinoma and adenocarcinoma since 2005 can be explained by a concomitant decrease in the number of cases classified as other non-small cell carcinoma. Black males continue to be disproportionally affected by squamous LCs, and blacks continue to be diagnosed with more advanced cancers than whites., Conclusions: LC incidence by histology continues to change over time. Additional variations are expected as screening becomes disseminated. It is important to continue to monitor LC rates to evaluate the impact of screening on current trends, assess the continuing benefits of tobacco control, and focus efforts on reducing racial disparities.

Background: Lung cancer incidence rates overall are declining in the United States. This study investigated the trends by histologic type and demographic characteristics., Methods: Surveillance, Epidemiology, and End Results (SEER) program rates of microscopically confirmed lung cancer overall and squamous cell, small cell, adenocarcinoma, large cell, other, and unspecified carcinomas among US whites and blacks diagnosed from 1977 to 2010 and white non-Hispanics, Asian/Pacific Islanders, and white Hispanics diagnosed from 1992 to 2010 were analyzed by sex and age., Results: Squamous and small cell carcinoma rates declined since the 1990s, although less rapidly among females than males. Adenocarcinoma rates decreased among males and only through 2005, after which they then rose during 2006 to 2010 among every racial/ethnic/sex group; rates for unspecified type declined. Male/female rate ratios declined among whites and blacks more than among other groups. Recent rates among young females were higher than among males for adenocarcinoma among all racial/ethnic groups and for other specified carcinomas among whites., Conclusions: US lung cancer trends vary by sex, histologic type, racial/ethnic group, and age, reflecting historical cigarette smoking rates, duration, cessation, cigarette composition, and exposure to other carcinogens. Substantial excesses among males have diminished and higher rates of adenocarcinoma among young females have emerged as rates among males declined more rapidly. The recognition of EGFR mutation and ALK rearrangements that occur primarily in adenocarcinomas are the primary basis for the molecular revolution that has transformed lung cancer diagnosis and treatment over the past decade, and these changes have affected recent type-specific trends., (© 2014 American Cancer Society.)

Lung cancer is an inflammation-associated epithelial carcinoma. A highly active interleukin 6 (IL-6)/glycoprotein 130 (gp130)/signal transducer and activator of transcription 3 (STAT3) pathway has been identified in a subset of primary lung cancer and closely correlated with tumor progression and poor prognosis. In a previous study, the frequent occurrence of somatic gain-of-function mutations was observed in the gp130-encoding IL6ST gene in exon 6 in 60% of inflammatory hepatocellular adenomas. Prompted by this finding, we assessed 110 Chinese lung carcinomas using PCR and direct DNA sequencing but found no somatic mutation of IL6ST in exon 6. However, one new potential germline missense mutation c.599C>G was identified in one adenocarcinoma that harbors wild-type epidermal growth factor receptor and KRAS. Protein modeling analysis showed that this mutation might not affect the gp130 protein conformation. Moreover, activated STAT3 was observed in most of the lung tumor tissues at a higher level than that in matched normal lung tissues. In conclusion, the c.599C>G mutation may be a new single nucleotide polymorphism of IL6ST, but mutations in exon 6 of this gene are not apparently common genetic variations occurring and leading to constitutive activation of STAT3 in lung cancer., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Lung cancer is one of the most commonly diagnosed cancers and the most frequent cause of cancer-related death worldwide. In Iran, it ranks second and third as the cancer-causing death in men and women, respectively. We carried out this study to find out the demographic, clinical, and histological characteristics and risk factors of lung cancer in a referral tertiary center in Iran., Materials and Methods: A retrospective study was conducted on cases of primary lung cancer based on the results of registered cancer reports of cytological and pathological specimens between March 2001 and March 2012. Demographic variables, clinical manifestations, histology and location of tumors were determined based on the data found in the medical records of each patient. Definite or probable etiologic factors were identified. Data analysis was performed with SPSS version 16 and a p-value ≤ 0.05 was considered as significant., Results: A total of 203 patients, with a mean age of 65.7 years (SD=11.2), with primary lung cancer were identified, 81.3% being men. Of the total, 110 cases (54.2%) were living in urban areas. In 53.2% of cases, the site of tumor was on the right side and in 72.9% of cases the lesion was centrally located. The histological types of lung cancer were squamous cell carcinoma (SCC) in 107 cases (52.7%), adenocarcinoma (AC) in 30 cases (14.8%), and small cell carcinoma (SC) in 27 cases (13.3%). Significant correlations between the gender and residence, smoking, and the histological type and location (central or peripheral) of tumor were found. The percentage of smokers was 75.2% in men and 15.8% in women., Conclusions: Smoking was the most important risk factor and squamous cell carcinoma the most common histological type of lung cancer in our study. Male sex and being a smoker was associated with histological types of SCC while being nonsmoker had relationship with adenocarcinoma.

Aim and Background: To determine whether female patients operated on for non-small cell lung cancer (NSCLC) have a survival advantage compared to male patients., Methods and Study Design: We analyzed data from 1,426 prospectively collected patients submitted to lung resection for NSCLC between 1999 and 2008., Results: Two groups, including 1,014 male and 412 female patients, were compared. Female patients were significantly younger, were more frequently asymptomatic, were less likely to be smokers, had better preoperative respiratory function, had a lower frequency of COPD, and were less commonly affected by cardiovascular comorbidity than men. Adenocarcinoma was more frequently present and early pathological stage (stage IA) more frequently detected in women at diagnosis. The operative mortality was significantly lower among women (1.6% vs 4.6%) (P = 0.012), and women underwent significantly more segmentectomies and fewer pneumonectomies (P = 0.001). The disease-related 5-year survival rate was significantly higher in women (66% vs 51%) (P = 0.0008). At univariate analysis the absence of symptoms at presentation, lower pathological stage, squamous cell type, and female gender were positive factors influencing long-term survival. At multivariate analysis low pathological stage, squamous cell type and female gender were confirmed as independent positive prognostic predictors. Women had a significant survival advantage irrespective of the histological subtype at pathological stage IA, IB, IIB and IIIA disease (P <0.05)., Conclusions: Female gender was confirmed to be a particular subset amongst patients affected by NSCLC and exerted a positive effect on disease-related survival of patients submitted to surgical resection. This important effect of gender should be cautiously kept in mind in analyzing the results of current and future trials for lung cancer therapy.

The WW domain-containing oxidoreductase (WWOX) gene is an identified tumor suppressor gene, of which several single nucleotide polymorphisms have been reported to contribute to cancer susceptibility. We hypothesized that genetic variations in WWOX are associated with lung cancer risk. In two independent case-control studies conducted in southern and eastern Chinese, we genotyped five tagSNPs of WWOX gene (rs10220974C > T, rs3764340C > G, rs12918952G > A, rs383362G > T, and rs12828G > A) in 1,559 lung cancer cases and 1,679 controls. Logistic regression analysis showed that two tagSNPs (rs3764340C > G; rs383362G > T) were significantly associated with lung cancer risk in dominant model (rs3764340C > G, GC/GG vs. CC: adjust OR = 1.35, 95% CI = 1.11-1.65; rs383362G > T, TG + TT vs. GG: adjust OR = 1.33, 95% CI = 1.14-1.55). The haplotype analysis further shown that the haplotype "G-T" was associated with the highest increased risk of lung cancer (OR = 2.20; 95% CI = 1.43-3.37). After combined these two loci, the number of the risk genotypes was associated with increased cancer risk in a dose-response manner (Ptrend  = 3.16 × 10(-6) ). In addition, a gene-based association analysis by using VEGAS software suggested the WWOX as a susceptible gene for lung cancer (P = 0.009). However, for rs10220974C > T, rs12918952G > A, and rs12828G > A, no significant association was observed for lung cancer risk. Taken together, our data suggested that genetic variants in WWOX may be genetic biomarkers for susceptibility to lung cancer., (© 2012 Wiley Periodicals, Inc.)

Background: Tall cell variant (TCV) and diffuse sclerosing variant (DSV) of papillary thyroid cancer are aggressive subtypes, for which tumors ≤1 cm have not been exclusively studied., Methods: The SEER database (1988-2009) was used to compare characteristics of TCV ≤1 cm (mTCV) and DSV ≤1 cm (mDSV) with classic papillary thyroid microcarcinoma (mPTC). Survival was analyzed with the Kaplan-Meier method and log-rank test, and risk factors for nodal metastases with chi-square analysis and binary logistic regression., Results: There were 97 mTCV, 90 mDSV, and 18,260 mPTC patients. mTCV incidence increased by 79.9% (p=0.153) over the study period, while mDSV incidence decreased by 10.3% (p=0.315). Compared to classic mPTC, mTCV tended to be larger on average (7.1 mm vs. 5.3 mm, p<0.001), with higher rates of multifocality (47.2% vs. 34.0% respectively, p=0.018) and lymph-node examination (63.9% vs. 39.2% respectively, p<0.001), while in mDSV, nodal metastases were more frequent (57.1% vs. 33.1% respectively, p=0.007). Both aggressive variants had higher rates of extrathyroidal extension (27.8% mTCV vs. 13.3% mDSV vs. 6.1% mPTC, p<0.001). Aggressive variants also received radioactive iodine more frequently (39.2% mTCV vs. 40.0% mDSV vs. 29.1% mPTC, p<0.001). However, they were not statistically more likely to receive thyroidectomy over lobectomy compared to classic mPTC. There were no significant differences in overall and disease-specific survival between the histologies. In mTCV, after adjustment, extrathyroidal extension was independently associated with size >7 mm (odds ratio (OR) 4.4 [CI 1.5-13.6]) and nodal metastasis with multifocality (OR 5.4 [CI 1.3-23.4]) and extrathyroidal extension (OR 5.8 [CI 1.3-25.4]). No statistically significant predictors of extrathyroidal extension or nodal metastasis in mDSV were observed., Conclusions: Aggressive variants of mPTC tend to exhibit more aggressive pathologic characteristics than classic mPTC, but survival appears to be similar. Treatment with total thyroidectomy and central lymphadenectomy may be warranted if the diagnosis can be made pre- or intraoperatively.

Background: The epidemiological study of basal cell carcinomas (BCCs) is difficult because BCCs lack distinct disease codes and are excluded from most cancer registries., Objective: To develop and validate a large BCC registry based on electronically assigned Systematized Nomenclature of Medicine (SNOMED) codes and text-string searches of electronic pathology reports from Kaiser Permanente Northern California., Methods and Materials: Potential BCCs were identified from electronic pathology reports (n=39,026) in 2005 and were reviewed by a dermatologist who assigned case/non-case status (gold-standard). A subset of the records (n=9,428) was independently reviewed by a second dermatologist to ascertain reliability of case assignment. In addition, a subset of excluded electronic pathology reports from 2005 (n=2,700) was reviewed to determine whether inclusion criteria had missed potential BCCs. We calculated the positive predictive value (PPV) of 3 different algorithms for identifying BCCs from electronic pathology data., Results: BCC-specific SNOMED codes had the highest PPV for identifying BCCs, 0.992 (95 percent CI: 0.991-0.993). Inter-rater reliability for case assignment was high (kappa=0.92, 95 percent CI: 0.91-0.93). Standardized incidence rates were consistent with previously published rates in the United States., Conclusions: We created and validated a large BCC registry to serve as a unique resource for studying BCCs.

Evidence about the role for reproductive and hormonal factors in the etiology of lung cancer in women is conflicting. To clarify this question, we examined 407 female cases and 499 female controls from the Environment And Genetics in Lung cancer Etiology population-based case-control study. Subjects were interviewed in person using a computer-assisted personal interview to assess demographics, education, smoking history, medical history, occupational history, reproductive and hormonal factors. Associations of interest were investigated using logistic regression models, adjusted for catchment area and age (matching variables), cigarette smoking (status, pack-years and time since quitting). Additional confounding variables were investigated but did not substantially affect the results. We observed a reduced risk of lung cancer among women with later age at first live birth [≥31 years: odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.31-1.06, p-trend = 0.05], later age at menopause (≥51 years: OR = 0.49, 95%CI = 0.31-0.79, p-trend = 0.003) and longer reproductive periods (≥41 years: OR = 0.44, 95%CI = 0.25-0.79, p-trend = 0.01). A reduced risk was also observed for hormone replacement therapy (OR = 0.63, 95%CI = 0.42-0.95, p = 0.03) and oral contraceptive use (OR = 0.67, 95%CI = 0.45-1.00, p = 0.05) but no trend with duration of use was detected. Menopausal status (both natural and induced) was associated with an augmented risk. No additional associations were identified for other reproductive variables. This study suggests that women who continue to produce estrogens have a lower lung cancer risk. Large studies with great number of never smoking women, biomarkers of estrogen and molecular classification of lung cancer are needed for a more comprehensive view of the association between reproductive factors and lung cancer risk., (Copyright © 2012 UICC.)

Introduction: Lung cancer incidence is associated with markers of lower socioeconomic status (SES) in whites, blacks, and Asians but with markers of higher SES in Hispanics. The magnitude and etiology of this positive gradient in Hispanics remain undefined. We examined non-small-cell lung cancer (NSCLC) incidence and ever-smoking rates among California Hispanics according to measures of SES., Methods: We computed neighborhood (n)SES-specific incidence rates by sex and race or ethnicity for 74,179 NSCLC cases in the California Cancer Registry, 1998-2002. Associations between nSES and NSCLC incidence were examined, using incidence rate ratios and linear trend tests, and stratified by age, stage, and histology. Ever-smoking rates among Hispanics were obtained from California Health Interview Survey 2001 data, and odds ratios for ever-smoking were calculated for measures of SES and acculturation., Results: Compared with the lowest nSES quintile, the NSCLC incidence in the highest quintile was 1.86 and 1.18 times higher for Hispanic women and men, respectively. The positive nSES gradients remained significant for all ages, stages, and nonsquamous histologies in women, and only for older age, local or regional stages, and adenocarcinoma histology in men. Ever-smoking rates were associated with English-speaking households and U.S.-born status for Hispanic women and low education and U.S.-born status for Hispanic men., Conclusions: For California Hispanics, higher nSES was strongly associated with increased NSCLC incidence in women, but weakly associated in men, and ever-smoking rates were strongly correlated with increased acculturation. This finding may portend an increasing burden of NSCLC in Hispanic women, given future trends in acculturation and SES.

Geographical and socio-economic factors such as climate, culture, ethnic origin, diet and life style such as smoking have been noted to influence the occurrence of bronchial carcinoma. We conducted this study to document the frequency of various histological types of bronchial carcinoma and correlated it with their demographic characteristics. This descriptive study was carried out among admitted patient with the suspicion of Bronchial carcinoma from January 2010 to January 2011 in medicine units of Mymensingh Medical College Hospital, Mymensingh. Among those only 30 consecutive histopathologically &/or cytological confirmed cases of Bronchial carcinoma were included in the study. No age, gender, environmental or occupational limits were applied for the selection of patients. Patients already diagnosed by some other hospital presenting to our unit with complications were not included in the study. Age rang were 26-70 years. Majority of patients i.e. 63.33% (n=19) were found to be in their fourth and sixth decade of life. Males were 86.66% (n=26) as compared to females 13.44% (n=4) and male to female ratio were 6.5:1. The majority of the patients were belonged to urban areas 63.34% (n=19), while 36.66% (n=11) came from the Rural population. In this study smokers were 86.66% (n=26) and nonsmokers were 13.33% (n=4). In Occupational distribution farmers were 33.33% (n=10), service holders were 20% (n=6), businessman were 16.66% (n=5), all the female were house wife 13.33% (n=4). Specimens for histopathological study were collected by trans-thoracic needle aspiration under CT or ultrasono-guided. The results of cell types in histopathologically proven 30 Bronchial carcinoma patients were; 10(33.36%) adenocarcinoma, 7(23.33%) squamous cell carcinoma, 6(20%) small cell carcinoma, 4(13.33%) large cell carcinoma and 3(10%) non-small cell carcinoma.

Purpose: The aim of this study was to evaluate any association of GSTM1 and GSTT1 null genotypes with the risk of lung cancer in a South Korean population., Methods: We conducted a large-scale, population-based case-control study including 3,933 lung cancer cases and 1,699 controls. Genotypes of GSTM1 and GSTT1 were determined using real-time polymerase chain reaction., Results: In logistic regression analysis adjusted for age and smoking, we did not find any association between GSTM1 or GSTT1 and LC risk in women. However, in men, the GSTM1 and GSTTI null genotypes were borderline associated with risk (OR=1.18, 95% CI=0.99-1.41 for GSTM1, OR=1.18, 95% CI=0.99-1.41 for GSTT1), and combined GSTM1 and GSTT1 null genotypes conferred an increased risk for LC in men (OR=1.39, 95% CI=1.08-1.78). The OR for the GSTT1 null genotype was greater in subjects aged 55 years old or younger (OR=1.45, 95% CI=1.09-1.92 for men; OR=1.36, 95% CI=0.97-1.90 for women), than in those over age 55 (OR=1.03, 95% CI=0.83-1.27 for men; OR=0.86, 95% CI=0.66-1.12 for women) in both genders (p for interaction <0.05)., Conclusions: In the Korean population, the GSTM1 and GSTT1 null genotypes are risk factors for LC in men; the GSTT1 null genotype has a more prominent effect on LC risk in younger people (age 55 years and under) than in older individuals.

Introduction and Objective: Residential radon is the second most important risk factor for lung cancer and the first among never-smokers. The objective of this study is to report the concentrations of residential radon in a series of never-smoker cases recruited in a multicenter study of cases and controls in northwestern Spain. In this study, all the hospitals in the Spanish province of Galicia and one from Asturias participated., Patients and Methods: The present article includes a series of cases with residential radon measurements. All the subjects were personally interviewed, 3 ml of blood were taken from each, and they were each given instructions about how to place a residential radon detector in their homes., Results: Sixty-nine case subjects were recruited, 84% of whom were women with a mean age of 71, and 81% of whom had adenocarcinoma. The average concentration of residential radon in the cases was 237 Bq/m(3), while the average concentration in the Galician population is 79 Bq/m(3). No relationship was observed between the concentration of residential radon and either sex or age at the time of diagnosis of the cases, but there was a tendency towards having a greater concentration in those diagnosed with small-cell and large-cell carcinoma., Conclusions: The concentrations of residential radon in the cases included are very high at about three times the average concentration of residential radon to which the general population of Galicia is exposed., (Copyright © 2012 SEPAR. Published by Elsevier España, S.L. All rights reserved.)