Pulmonary Large Cell Neuroendocrine Carcinoma.

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.

Impact of different patterns of metastasis in non-small-cell lung cancer patients.

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.

Metformin use and lung cancer survival: a population-based study in Norway.

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.

Rising Incidence of Lung Cancer in Arab Females, Jewish Females, and Arab Males from 1990 to 2014 in Israel.

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.

Diesel Engine Exhaust Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Exposure-Response Analysis of 14 Case-Control Studies.

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/m3 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.

Clinical characteristics and prognosis of pulmonary large cell carcinoma: A population-based retrospective study using SEER data.

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.

Adjuvant chemotherapy improves the prognosis of early stage resectable pulmonary large cell carcinoma: analysis of SEER data.

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.

Lung Cancer in the Young.

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.

Comorbidities and relevant outcomes, commonly associated with cancer, of patients newly diagnosed with advanced non-small-cell lung cancer in Sweden.

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.

Large-Cell Neuroendocrine Carcinoma of the Lung: A Population-Based Study.

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.

Lung Cancer Incidence and Mortality with Extended Follow-up in the National Lung Screening Trial.

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.

Lung Large Cell Neuroendocrine Carcinoma: An Analysis of Patients from the Surveillance, Epidemiology, and End-Results (SEER) Database.

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.

Characteristics of 252 patients with bronchopulmonary neuroendocrine tumours treated at the Copenhagen NET Centre of Excellence.

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.

Prevalence and prognostic value of PD-L1 expression in molecular subtypes of metastatic large cell neuroendocrine carcinoma (LCNEC).

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.

Nomogram based on homogeneous and heterogeneous associated factors for predicting bone metastases in patients with different histological types of lung cancer.

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.

Circulating high sensitivity C reactive protein concentrations and risk of lung cancer: nested case-control study within Lung Cancer Cohort Consortium.

OBJECTIVES: To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. DESIGN: Nested case-control study. SETTING: 20 population based cohort studies in Asia, Europe, Australia, and the United States. PARTICIPANTS: 5299 patients with incident lung cancer, with individually incidence density matched controls. EXPOSURE: Circulating hsCRP concentrations in prediagnostic serum or plasma samples. MAIN OUTCOME MEASURE: Incident lung cancer diagnosis. RESULTS: A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. CONCLUSIONS: Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.

Role of Low-Dose Computerized Tomography in Lung Cancer Screening among Never-Smokers.

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.

Lung cancer in Spanish women: The WORLD07 project.

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.

Factors Associated With Treatment of Clinical Stage I Non-Small-cell Lung Cancer: A Population-based Analysis.

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.

[Diagnosis and treatment of the neuroendocrine tumors of the lung]. / A tüdõ neuroendokrin daganatainak diagnózisa és kezelése.

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.