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Recent research on the relationship between the immune system and cancer has revealed the molecular mechanisms by which cancer cells co-opt certain T cell receptors which block the cytotoxic response to defend themselves from the antitumor immune attack. These findings have helped identify specific targets (T cell receptors or their corresponding ligands) for the design of monoclonal antibodies that can unlock the immune response. These drugs, known as immune checkpoint inhibitors, have shown efficacy in metastatic melanoma and kidney cancer, and have been successfully tested in non-small cell lung cancer in recent trials. Immune checkpoint inhibitors were included in clinical practice as a second-line option after an initial chemotherapy (CT) regimen, and in the last year positive results have been reported from randomized trials in which they were compared in first line with standard CT. Responses have been surprising and durable, but less than 20%-25% in unselected patients, so it is essential that factors predicting efficacy be identified. One such biomarker is PD-L1, but the different methods used to detect it have produced mixed results. This non-systematic review discusses the results of the latest trials, the possibilities of incorporating these drugs in first-line regimens, the criteria for patient selection, adverse effects, and the prospects of combinations with conventional treatment modalities, such as CT, radiation therapy, and antiangiogenic agents., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

The Thoracic Surgery and Thoracic Oncology groups of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) have backed the publication of a handbook on recommendations for the diagnosis and treatment of non-small cell lung cancer. Due to the high incidence and mortality of this disease, the best scientific evidence must be constantly updated and made available for consultation by healthcare professionals. To draw up these recommendations, we called on a wide-ranging group of experts from the different specialties, who have prepared a comprehensive review, divided into 4 main sections. The first addresses disease prevention and screening, including risk factors, the role of smoking cessation, and screening programs for early diagnosis. The second section analyzes clinical presentation, imaging studies, and surgical risk, including cardiological risk and the evaluation of respiratory function. The third section addresses cytohistological confirmation and staging studies, and scrutinizes the TNM and histological classifications, non-invasive and minimally invasive sampling methods, and surgical techniques for diagnosis and staging. The fourth and final section looks at different therapeutic aspects, such as the role of surgery, chemotherapy, radiation therapy, a multidisciplinary approach according to disease stage, and other specifically targeted treatments, concluding with recommendations on the follow-up of lung cancer patients and surgical and endoscopic palliative interventions in advanced stages., (Copyright © 2016 SEPAR. Published by Elsevier Espana. All rights reserved.)

Introduction and Objectives: As cancer survival improves, the appearance of multiple tumors in a single patient is becoming more common. The aim of this study was to analyze long-term evolution, focusing particularly on disease recurrence and second primary tumors, in patients with lung cancer (LC) and ≥ 3 years overall survival., Material and Methods: Retrospective study of 1,769 patients with LC. A total of 218 (136 treated with surgery and 82 with other treatments), followed up for between 5 and 23 years were enrolled. LC progress and intercurrent diseases were recorded., Results: A total of 65 patients presented tumor relapse, of which 60.9% occurred in the first 3 years; 26 patients developed secondary primary tumors (84.6% after 5 years) and 24 developed 2 or more second extrapulmonary tumors (66.6% after 5 years), most of which were smoking-related. The incidence of second primaries was greater than the expected incidence of cancer in the general population matched for age and sex., Conclusion: The multiple carcinogenic effect of smoking persists and manifests in various organs, more than 5 years after the diagnosis of LC, even in patients with long survival. After 5 years, a second tumor is more likely than a relapse of the primary disease, and the lung is the most common site of development of a second tumor., (Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.)

Pulmonary neuroendocrine tumors (PNT) encompass a broad spectrum of tumors including typical carcinoid (TC) and atypical (AC) tumors, large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC). Although no variety can be considered benign, AC and TC have a much lower metastatic potential, are usually diagnosed in early stages, and most are candidates for surgical treatment. Several chemotherapy (CT) regimens are available in the case of recurrence or in advanced stages, although scientific evidence is insufficient. LCNEC, which is currently classified alongside large-cell carcinomas, have molecular features, biological behavior and CT sensitivity profile closely resembling SCLC. Pathological diagnosis is often difficult, despite the availability of immunohistochemical techniques, and surgical specimens may be necessary. The diagnostic tests used are similar to those used in other lung tumors, with some differences in the optimal tracer in positron emission tomography. The new TNM classification is useful for staging these tumors. Carcinoid syndrome, very rare in PNT, may cause symptoms that are difficult to control and requires special therapy with somatostatin analogs and other drugs. Overall, with the exception of SCLC, new trials are needed to provide a response to the many questions arising with regard to the best treatment in each lineage and each stage., (Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.)

Introduction: The current edition of the tumor, node and metastasis (TNM) classification of lung cancer (LC) divides the presence of metastasis (M1) into two categories: M1a and M1b, depending on its anatomical location. To assess this new classification, the survival and the M descriptors of LC patients with metastatic disease registered by the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery II (GCCB-S-II), were analyzed., Methods: Non-small cell lung cancer (NSCLC) patients, with M1a or M1b disease, included in the GCCB-S-II, from April 2009 to December 2010, staged in accordance with the prospective staging project protocol of the International Association for the Study of Lung Cancer (IASLC), and with complete TNM staging and follow-up data, were studied. The overall survival associated with each M1 category and each M descriptor, besides other prognostic factors (sex, age, performance status [PS] and others) were analyzed by univariate and multivariate models., Results: 640 NSCLC patients (195 M1a and 445 M1b) were included. M1b tumors had significantly worse survival than M1a tumors (p < 0.001). The prognostic value of M1 category was independent from other prognostic variables such as PS, weight loss, and others. The number of metastatic sites (isolated versus multiple) and the number of lesions (single versus multiple) in patients with isolated metastasis showed prognostic value, especially in those with brain metastasis., Conclusion: The current division of the M1 category into two subsets (M1a and M1b) is warranted by their prognostic significance. The number of metastatic sites and the number of lesions in patients with isolated metastasis should be taken into account, because they also have prognostic relevance., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Introduction and Objectives: The seventh edition of the TNM classification, together with undeniable advantages, has limitations. The International Association for the Study of Lung Cancer (IASLC) Staging Committee has designed an international prospective study to improve this classification. A group of thoracic surgeons and pulmonologists was established in the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) Oncology area, and created a registry of new lung cancer (LC) cases to participate in this project. The aim of this paper is to describe the main characteristics of the patients included., Materials and Methods: Prospective, observational, multicentre, multiregional data collection (epidemiological, clinical, therapeutic and, especially, anatomical extension) study, according to the IASLC protocol, to analyse its prognostic value., Results: Two thousand, four hundred and nineteen patients (83.6% men) from 28 hospitals were included. Ninety-six percent of the men and 54% of the women were smokers or ex-smokers. Chest/abdominal computed tomography (CT) scanning was performed in over 90% and positron emission tomography (PET)/CT scanning in 51.5% of cases. Among the 1035 patients who underwent surgery, 77% had early stages (ia to iib), and 61.6% of those treated using other methods had stage iv. Respiratory comorbidity was higher in men (47.9% versus 21.4%). The most common histological subtype was adenocarcinoma (34%), especially in non-smoking women (69.5%)., Conclusions: The proportion of women and adenocarcinomas, as well as those resected at an early stage, increased among LC cases in Spain., (Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.)

Objective: Mortality due to lung cancer in Spain is increasing continuously. The aim of the present study was to collect information on the hospital incidence of lung cancer, as well as information on clinical management, in different regions of Spain., Material and Methods: A prospective observational study of patients diagnosed with lung cancer in 2003 was carried out in 13 centers in 9 autonomous communities. Epidemiological, clinical, diagnostic, and therapeutic variables were assessed., Results: Of a total population of 2,726,601 inhabitants (1 346 483 men and 1 380 118 women), 1064 male and 125 female lung cancer patients were included. The incidence standardized to the world population varied between 42.4/100,000 and 61.8/100,000 in men and between 1.5/100,000 and 8.6/100,000 in women. Overall, 51% were aged over 70 years, and 97.5% of the men and 32% of the women were smokers or ex-smokers. Cytologic or histologic confirmation was obtained for 93.1% of the cases (20.8% of which were small cell lung cancers and 79.2% were non-small cell lung cancers). The main initial symptoms were cough, chest pain, and weight loss. In 13.7%, lung cancer was suspected because of abnormal chest x-ray. The percentage with clinical TNM stages I and II ranged from 6.3% to 26.9%. The most common stage was stage IV in all centers. The percentage of patients undergoing surgery ranged from 2.5% to 20.6%, with a mean of 14.8% (19.9% of whom were patients with non-small cell lung cancer); 27% received palliative treatment only., Conclusions: The proportion of women suffering from lung cancer increased with respect to previous studies, with notable differences among regions. Despite diagnostic improvements, the percentage of patients undergoing surgery is low, though interregional variation is considerable.

Objectives: Our main objective was to determine the incidence of bronchopulmonary cancer in Extremadura (Spain). We also studied the presence of risk factors such as smoking and exposure to other carcinogens., Material and Methods: This prospective study used a protocol followed by all hospitals in Extremadura; enrolled were patients with a diagnosis of bronchopulmonary carcinoma in 1998 who lived habitually in the region. Cyto-histological confirmation of the diagnosis was sought or, when such confirmation was unavailable, diagnostic agreement among researchers was based on clinical, radiological and/or endoscopic data., Results: The incidences adjusted to world population were 53.4, 2.16 and 25.3 per 100,000 inhabitants for men, women and the entire population sample, respectively. Patterns in the provinces of Cáceres and Badajoz were very similar. Of 433 cases recorded, 95% were men and 78% were aged 60 years or older. Cyto-histological confirmation of diagnosis was available for 92.2%. Most tumors were epidermoid (41.1%). The time between the start of smoking and diagnosis was significantly shorter in heavier smokers.

We evaluated the diagnostic utility of the carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC Ag.) in malignant pleural effusion (MPE). CEA, NSE and SCC Ag, blood and pleural levels were quantified by enzyme immunoassay (EIA) in 85 patients with pleural effusions: 35 non malignant pleural effusions, and 50 MPE; 42 with lung carcinoma (LC), and 8 with extrapulmonary carcinoma. The sensitivity and specificity was compared to cytological results of the pleural fluid. The sensitivities of CEA7 NSE and SCC Ag. (in pleural fluid) were 59.5%, 48.7% and 16.7% respectively in patients with LC (specificity higher than 90%). Using a combination with CEA and NSE, the sensitivity reached 80.9% (specificity, 91.4%). The cytology of pleural fluid was positive in 45.2%. The pleural/blood ratios did not improve the diagnostic performance. In patients with extrapulmonary carcinoma, the sensitivity of these tumor markers was lower. The combination of CEA and NSE pleural levels is useful in the diagnostic approach to the patient with pleural effusion. A high level of NSE is suggestive of small cell lung cancer (SCLC).

The utility of neuron-specific enolase (NSE) for the diagnosis and management of small cell lung cancer (SCLC) is analyzed. Serum concentrations of NSE were measured in 69 healthy adults, 106 patients with non-neoplastic pneumopathy (NNP), 16 with pulmonary metastasis of extrapulmonary origin (PMEO), 126 with non-small cell lung cancer (NSCLC), and 77 with SCLC. Repeated analyses were carried out for patients in the last group during and after treatment, and survival time was recorded. NSE was high in 77.6% of patients with SCLC [50% in cases with limited disease (LD) and 93.6% in those with extensive disease (ED)]. NSE was high in 10.3% of those with NSCLC, in 11.5% of those with PMEO, and in 2.8% of those with NNP. NSE decreased 100% in SCLC patients achieving full remission after treatment and in 25% of those responding poorly. Later, this marker increased in 81.2% of those experiencing relapse, and in 6.2% of these the increased preceded symptoms. Initial NSE concentrations had prognostic value (p = 0.003) that was independent of disease stage (LD or ED). NSE is of great diagnostic and prognostic value in SCLC, accurately reflecting tumor size. Posttreatment changes closely parallel disease activity.

During the last 5 years (1982-1986), a diagnosis of primary bronchopulmonary cancer was made in 157 patients. The mean rate of incidence for males in our province was 25.7 per 100,000 and per year. Among patients with neoplasia, the rate of smokers approached 100%. There was a direct relation between younger age at presentation and higher number of cigarettes per day. In ex-smokers the clinical development of the disease was later than in current smokers. The results regarding the following variables are also reported: professional background, past history, initial symptoms, time to diagnosis (for each histologic type) and radiological findings.