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Small cell lung cancer (SCLC) is an aggressive malignancy composed of distinct transcriptional subtypes, but implementing subtyping in the clinic has remained challenging, particularly due to limited tissue availability. Given the known epigenetic regulation of critical SCLC transcriptional programs, we hypothesized that subtype-specific patterns of DNA methylation could be detected in tumor or blood from SCLC patients. Using genomic-wide reduced-representation bisulfite sequencing (RRBS) in two cohorts totaling 179 SCLC patients and using machine learning approaches, we report a highly accurate DNA methylation-based classifier (SCLC-DMC) that can distinguish SCLC subtypes. We further adjust the classifier for circulating-free DNA (cfDNA) to subtype SCLC from plasma. Using the cfDNA classifier (cfDMC), we demonstrate that SCLC phenotypes can evolve during disease progression, highlighting the need for longitudinal tracking of SCLC during clinical treatment. These data establish that tumor and cfDNA methylation can be used to identify SCLC subtypes and might guide precision SCLC therapy.
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Ácidos Nucleicos Livres , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metilação de DNA , Ácidos Nucleicos Livres/genética , Epigênese Genética , Biomarcadores Tumorais/genéticaRESUMO
BACKGROUND: Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation. METHODS: A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council. RESULTS: Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements. CONCLUSIONS: This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Etiquetas de Sequências Expressas , Achados Incidentais , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation. METHODS: A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council. RESULTS: Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements. CONCLUSIONS: This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible.
Assuntos
Neoplasias Pulmonares , Guias de Prática Clínica como Assunto , Humanos , Detecção Precoce de Câncer/métodos , Etiquetas de Sequências Expressas , Achados Incidentais , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Although tumor-infiltrating T cells represent a favorable prognostic marker for cancer patients, the majority of these cells are rendered with an exhausted phenotype. Hence, there is an unmet need to identify factors which can reverse this dysfunctional profile and restore their anti-tumorigenic potential. Activin-A is a pleiotropic cytokine, exerting a broad range of pro- or anti-inflammatory functions in different disease contexts, including allergic and autoimmune disorders and cancer. Given that activin-A exhibits a profound effect on CD4+ T cells in the airways and is elevated in lung cancer patients, we hypothesized that activin-A can effectively regulate anti-tumor immunity in lung cancer. METHODS: To evaluate the effects of activin-A in the context of lung cancer, we utilized the OVA-expressing Lewis Lung Carcinoma mouse model as well as the B16F10 melanoma model of pulmonary metastases. The therapeutic potential of activin-A-treated lung tumor-infiltrating CD4+ T cells was evaluated in adoptive transfer experiments, using CD4-/--tumor bearing mice as recipients. In a reverse approach, we disrupted activin-A signaling on CD4+ T cells using an inducible model of CD4+ T cell-specific knockout of activin-A type I receptor. RNA-Sequencing analysis was performed to assess the transcriptional signature of these cells and the molecular mechanisms which mediate activin-A's function. In a translational approach, we validated activin-A's anti-tumorigenic properties using primary human tumor-infiltrating CD4+ T cells from lung cancer patients. RESULTS: Administration of activin-A in lung tumor-bearing mice attenuated disease progression, an effect associated with heightened ratio of infiltrating effector to regulatory CD4+ T cells. Therapeutic transfer of lung tumor-infiltrating activin-A-treated CD4+ T cells, delayed tumor progression in CD4-/- recipients and enhanced T cell-mediated immunity. CD4+ T cells genetically unresponsive to activin-A, failed to elicit effective anti-tumor properties and displayed an exhausted molecular signature governed by the transcription factors Tox and Tox2. Of translational importance, treatment of activin-A on tumor-infiltrating CD4+ T cells from lung cancer patients augmented their immunostimulatory capacity towards autologous CD4+ and CD8+ T cells. CONCLUSIONS: In this study, we introduce activin-A as a novel immunomodulatory factor in the lung tumor microenvironment, which bestows exhausted CD4+ T cells with effector properties.
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Ativinas/administração & dosagem , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Imunidade Celular/efeitos dos fármacos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/metabolismo , Contagem de Linfócitos , Transferência Adotiva , Animais , Biomarcadores , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Suscetibilidade a Doenças , Regulação Neoplásica da Expressão Gênica , Proteínas HMGB/genética , Proteínas HMGB/metabolismo , Humanos , Imunofenotipagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Camundongos , Camundongos Transgênicos , Transdução de SinaisRESUMO
There is a substantial burden of chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), in low- and middle-income countries (LMICs). LMICs have particular challenges in delivering cost-effective prevention, diagnosis, and management of COPD. Optimal care can be supported by effective implementation of guidelines. This American Thoracic Society workshop considered challenges to implementation of COPD guidelines in LMICs. We make 10 specific recommendations: 1) relevant organizations should provide LMIC-specific COPD management guidance; 2) patient and professional organizations must persuade policy-makers of the importance of lung function testing programs in LMICs; 3) healthcare education and training should emphasize the early-life origins of COPD; 4) urgent action is required by governments to reduce airborne exposures, including exposures to tobacco smoke and indoor and outdoor air pollution; 5) guidance for COPD in LMICs should explicitly link across Essential Medicine Lists and the World Health Organization package of essential noncommunicable disease interventions for primary health care in low-resource settings and should consider availability, affordability, sustainability, and cost-effective use of medicines; 6) the pharmaceutical industry should work to make effective COPD and tobacco-dependence medicines globally accessible and affordable; 7) implementation of locally adapted, cost-effective pulmonary rehabilitation programs should be an international priority; 8) the World Health Organization Global Action Plan for the Prevention and Control of Noncommunicable Diseases should specify how improvements in respiratory health will be achieved; 9) research funders should increase the proportion of funding allocated to COPD in LMICs; and 10) the respiratory community should leverage the skills and enthusiasm of earlier-career clinicians and researchers to improve global respiratory health.
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Países em Desenvolvimento , Doença Pulmonar Obstrutiva Crônica , Humanos , Renda , Pobreza , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Sociedades , Estados UnidosRESUMO
AIM: Lung cancer screening reduces mortality. We aim to validate the performance of Lung EpiCheck, a six-marker panel methylation-based plasma test, in the detection of lung cancer in European and Chinese samples. METHODS: A case-control European training set (n=102 lung cancer cases, n=265 controls) was used to define the panel and algorithm. Two cut-offs were selected, low cut-off (LCO) for high sensitivity and high cut-off (HCO) for high specificity. The performance was validated in case-control European and Chinese validation sets (cases/controls 179/137 and 30/15, respectively). RESULTS: The European and Chinese validation sets achieved AUCs of 0.882 and 0.899, respectively. The sensitivities/specificities with LCO were 87.2%/64.2% and 76.7%/93.3%, and with HCO they were 74.3%/90.5% and 56.7%/100.0%, respectively. Stage I nonsmall cell lung cancer (NSCLC) sensitivity in European and Chinese samples with LCO was 78.4% and 70.0% and with HCO was 62.2% and 30.0%, respectively. Small cell lung cancer (SCLC) was represented only in the European set and sensitivities with LCO and HCO were 100.0% and 93.3%, respectively. In multivariable analyses of the European validation set, the assay's ability to predict lung cancer was independent of established risk factors (age, smoking, COPD), and overall AUC was 0.942. CONCLUSIONS: Lung EpiCheck demonstrated strong performance in lung cancer prediction in case-control European and Chinese samples, detecting high proportions of early-stage NSCLC and SCLC and significantly improving predictive accuracy when added to established risk factors. Prospective studies are required to confirm these findings. Utilising such a simple and inexpensive blood test has the potential to improve compliance and broaden access to screening for at-risk populations.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Biomarcadores Tumorais , China , Detecção Precoce de Câncer , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico , Metilação , Estudos ProspectivosRESUMO
BACKGROUND: Accurate mediastinal staging in patients with non-small cell lung cancer (NSCLC) is crucial for the determination of optimal treatment management. METHODS: This was a real-life prospective study enrolling 140 patients between December 2016 and August 2018. We aimed to determine the clinical utility of EBUS/EUS-b in mediastinal staging of patients with NSCLC in comparison with integrated PET/CT. Furthermore, SUVmax cut-off value with the highest specificity/accuracy was evaluated. Subgroup analysis according to histological type was performed. RESULTS: One hundred and thirty patients were eligible for analysis (mean age ± SD: 67.6±7.6, males 97). Three hundred different lymph node stations were sampled (272 through EBUS-TBNA and 28 through EUS-b FNA). Mean SUVmax of all malignant lymph nodes was 7.46 (SD =5.54). Sensitivity, specificity, PPV and NPV of EBUS/EUS-b for the identification of mediastinal malignant lymph nodes was 93.8%, 100%, 100%, and 93.4%, respectively. Accordingly, PET/CT yielded 92.2% sensitivity, 43.9% specificity, 64.8% PPV and 83.3% NPV. For adenocarcinoma (n=76) NPV were 86.2% with EBUS/EUS-b and 75% with PET/CT. NPV for squamous cell (n=46) was 100% with EBUS/EUS-b and 90.9% with PET/CT. EBUS/EUS-b staging yielded excellent agreement with final staging (97.5%, Tau 0.94, P<0.001). ROC curve analysis identified the value 4.95 as the optimal SUVmax cut-off value with the best specificity (87.4%) and accuracy (79%) (AUC 0.69; 95% CI: 0.73-0.84, P<0.001). CONCLUSIONS: Thoracic endosonography is an excellent, minimally invasive tool yielding high sensitivity and diagnostic accuracy in mediastinal staging of patients with NSCLC. Implementation of both EBUS/EUS-b and PET/CT is necessary before any surgical intervention.
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European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCC) are written by experts representing all disciplines involved in cancer care in Europe. They give patients, health professionals, managers and policymakers a guide to essential care throughout the patient journey. Lung cancer is the leading cause of cancer mortality and has a wide variation in treatment and outcomes in Europe. It is a major healthcare burden and has complex diagnosis and treatment challenges. Care must only be carried out in lung cancer units or centres that have a core multidisciplinary team (MDT) and an extended team of health professionals detailed here. Such units are far from universal in European countries. To meet European aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.
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Neoplasias Pulmonares , Atenção à Saúde , Europa (Continente) , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Qualidade da Assistência à SaúdeRESUMO
In Europe, lung cancer ranks third among the most common cancers, remaining the biggest killer. Since the publication of the first European Society of Radiology and European Respiratory Society joint white paper on lung cancer screening (LCS) in 2015, many new findings have been published and discussions have increased considerably. Thus, this updated expert opinion represents a narrative, non-systematic review of the evidence from LCS trials and description of the current practice of LCS as well as aspects that have not received adequate attention until now. Reaching out to the potential participants (persons at high risk), optimal communication and shared decision-making will be key starting points. Furthermore, standards for infrastructure, pathways and quality assurance are pivotal, including promoting tobacco cessation, benefits and harms, overdiagnosis, quality, minimum radiation exposure, definition of management of positive screen results and incidental findings linked to respective actions as well as cost-effectiveness. This requires a multidisciplinary team with experts from pulmonology and radiology as well as thoracic oncologists, thoracic surgeons, pathologists, family doctors, patient representatives and others. The ESR and ERS agree that Europe's health systems need to adapt to allow citizens to benefit from organised pathways, rather than unsupervised initiatives, to allow early diagnosis of lung cancer and reduce the mortality rate. Now is the time to set up and conduct demonstration programmes focusing, among other points, on methodology, standardisation, tobacco cessation, education on healthy lifestyle, cost-effectiveness and a central registry.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Análise Custo-Benefício , Europa (Continente) , Humanos , Neoplasias Pulmonares/diagnóstico , Sistema de RegistrosRESUMO
In Europe, lung cancer ranks third among the most common cancers, remaining the biggest killer. Since the publication of the first European Society of Radiology and European Respiratory Society joint white paper on lung cancer screening (LCS) in 2015, many new findings have been published and discussions have increased considerably. Thus, this updated expert opinion represents a narrative, non-systematic review of the evidence from LCS trials and description of the current practice of LCS as well as aspects that have not received adequate attention until now. Reaching out to the potential participants (persons at high risk), optimal communication and shared decision-making will be key starting points. Furthermore, standards for infrastructure, pathways and quality assurance are pivotal, including promoting tobacco cessation, benefits and harms, overdiagnosis, quality, minimum radiation exposure, definition of management of positive screen results and incidental findings linked to respective actions as well as cost-effectiveness. This requires a multidisciplinary team with experts from pulmonology and radiology as well as thoracic oncologists, thoracic surgeons, pathologists, family doctors, patient representatives and others. The ESR and ERS agree that Europe's health systems need to adapt to allow citizens to benefit from organised pathways, rather than unsupervised initiatives, to allow early diagnosis of lung cancer and reduce the mortality rate. Now is the time to set up and conduct demonstration programmes focusing, among other points, on methodology, standardisation, tobacco cessation, education on healthy lifestyle, cost-effectiveness and a central registry.Key Points⢠Pulmonologists and radiologists both have key roles in the set up of multidisciplinary LCS teams with experts from many other fields.⢠Pulmonologists identify people eligible for LCS, reach out to family doctors, share the decision-making process and promote tobacco cessation.⢠Radiologists ensure appropriate image quality, minimum dose and a standardised reading/reporting algorithm, together with a clear definition of a "positive screen".⢠Strict algorithms define the exact management of screen-detected nodules and incidental findings.⢠For LCS to be (cost-)effective, it has to target a population defined by risk prediction models.
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Consenso , Tomada de Decisões , Neoplasias Pulmonares/diagnóstico , Detecção Precoce de Câncer/métodos , Europa (Continente) , Humanos , Sistema de RegistrosRESUMO
BACKGROUND: Abundant evidence supports an association between Idiopathic Pulmonary Fibrosis (IPF) and lung cancer development. Data on diagnosis and management of patients with IPF and lung cancer are still scarce. PATIENTS AND METHODS: This was a retrospective multicenter study, enrolling 1016 patients with IPF from eight different centers between 2011 and 2018 in Greece. Our aim was to estimate prevalence of lung cancer in patients with IPF in Greece. RESULTS: We identified 102 cases of patients with IPF and lung cancer (prevalence = 10.03% n = 102/1016, mean age±SD = 71.8 ± 6.9, 96 males, mean FVC±SD = 72.7 ± 19.7, mean DLCO±SD = 44.5 ± 16.3). We identified 85 cases (83.3%) of non-small cell lung cancer (35 squamous, 28 adenocarcinoma), and 15 cases (14.7%) of small cell lung cancer. Primary lesion was localized in lower lobes in 57.1% of cases. Lung cancer was diagnosed post IPF diagnosis (mean latency time + SD = 33.2 + 36.1 months) in 57.6% of patients and synchronously in 36.5% of patients. Chemotherapy was applied in 26.7% of cases, while 34.7% of patients underwent surgery. Median survival of patients with IPF and lung cancer was 27.4 months (95% CI: 20.6 to 36.8). CONCLUSIONS: IPF is a risk factor for lung cancer development. In line with current literature, squamous cell carcinoma is the most common histologic subtype in patients with IPF. Large randomized controlled studies on the management of patients with IPF and lung cancer are sorely needed.
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Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/epidemiologia , Neoplasias Pulmonares/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Grécia , Humanos , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/patologia , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/patologia , SobrevidaRESUMO
In daily clinical practice, radiologists and pulmonologists are faced with incidental radiographic findings of pulmonary nodules. Deciding how to manage these findings is very important as many of them may be benign and require no further action, but others may represent early disease and importantly early-stage lung cancer and require prompt diagnosis and definitive treatment. As the diagnosis of pulmonary nodules includes invasive procedures which can be relatively minimal, such as bronchoscopy or transthoracic aspiration or biopsy, but also more invasive procedures such as thoracic surgical biopsies, and as these procedures are linked to anxiety and to cost, it is important to have clearly defined algorithms for the description, management, and follow-up of these nodules. Clear algorithms for the imaging protocols and the management of positive findings should also exist in lung cancer screening programs, which are already established in the USA and which will hopefully be established worldwide. This article reviews current knowledge on nodule definition, diagnostic evaluation, and management based on literature data and mainly recent guidelines.
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Rationale: Immune checkpoint inhibitors (ICIs) have revolutionized cancer care but are associated with unique adverse events, including potentially life-threatening pneumonitis. The diagnosis of ICI-pneumonitis is increasing; however, the biological mechanisms, clinical and radiologic features, and the diagnosis and management have not been well defined.Objectives: To summarize evidence, identify knowledge and research gaps, and prioritize topics and propose methods for future research on ICI-pneumonitis.Methods: A multidisciplinary group of international clinical researchers reviewed available data on ICI-pneumonitis to develop and refine research questions pertaining to ICI-pneumonitis.Results: This statement identifies gaps in knowledge and develops potential research questions to further expand knowledge regarding risk, biologic mechanisms, clinical and radiologic presentation, and management of ICI-pneumonitis.Conclusions: Gaps in knowledge of the basic biological mechanisms of ICI-pneumonitis, coupled with a precipitous increase in the use of ICIs alone or combined with other therapies, highlight the importance in triaging research priorities for ICI-pneumonitis.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Genes cdc/imunologia , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Pneumonia/induzido quimicamente , Pesquisa Biomédica , Humanos , Objetivos Organizacionais , Projetos de Pesquisa , Fatores de Risco , Sociedades Médicas , Estados UnidosRESUMO
INTRODUCTION: Improved outcome has been shown in patients with synchronous oligometastatic (sOM) NSCLC when treated with radical intent. As a uniform definition of sOM NSCLC is lacking, we developed a definition and diagnostic criteria by a consensus process. METHODS: A pan-European multidisciplinary consensus group was established. Consensus questions were built on the basis of current controversies, and definitions were extracted from a survey, cases and a systematic review. This statement was formulated during a consensus meeting. RESULTS: It was determined that definition of sOM NSCLC is relevant when a radical treatment that may modify the disease course (leading to long-term disease control) is technically feasible for all tumor sites with acceptable toxicity. On the basis of the review, a maximum of five metastases and three organs was proposed. Mediastinal lymph node involvement was not counted as a metastatic site. Fludeoxyglucose F 18 positron emission tomography-computed tomography and brain imaging were considered mandatory. A dedicated liver magnetic resonance imaging scan was advised for a solitary liver metastasis, and thoracoscopy and biopsies of distant ipsilateral pleural sites were recommended for a solitary pleural metastasis. For mediastinal staging, fludeoxyglucose F 18 positron emission tomography-computed tomography was deemed the minimum requirement, with pathological confirmation recommended if this influences the treatment strategy. Biopsy of a solitary metastatic location was mandated unless the multidisciplinary team is of the opinion that the risks outweigh the benefits. CONCLUSION: A multidisciplinary consensus statement on the definition and staging of sOM NSCLC has been formulated. This statement will help to standardize inclusion criteria in future clinical trials.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Consenso , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de NeoplasiasRESUMO
Dramatic progress in targeted therapy and immunotherapy has been changing clinical practices in lung cancer. With the accumulation of clinical practice, it has become clear that pre-existing interstitial pneumonia (IP) could be a risk factor for drug-induced lung injury, which has enhanced awareness regarding the difficulty in treating lung cancer with comorbid IP. Unfortunately, there is only low-grade evidence in the field of lung cancer with comorbid IP, because almost all clinical trials exclude such patients. There have been very few specialized clinical trials for patients with lung cancer and underlying IPs thus far. Therefore, it is necessary to treat such cases empirically or to give up on the treatment itself. Considering these circumstances, establishing how to treat lung cancer with comorbid IP is an urgent issue. This paper is a summary of the official statement reported by the Diffuse Lung Disease/Thoracic Oncology Assembly and the Japanese Respiratory Society (JRS) in 2017, which attempts to approach lung cancer with comorbid IP systematically.
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Doenças Pulmonares Intersticiais/terapia , Neoplasias Pulmonares/terapia , Pneumologia/organização & administração , Humanos , Japão/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Neoplasias Pulmonares/epidemiologiaRESUMO
INTRODUCTION: Diffuse parenchymal lung diseases (DPLD) constitute a heterogeneous group of disorders, sometimes requiring surgical lung biopsies (SLB) to obtain a definite diagnosis. Transbronchial cryobiopsy (TBCB) is a new promising interventional bronchoscopic method of obtaining lung tissue that is gaining ground against SLB. METHODS: Fifty consecutive patients with indeterminate DPLD (definite/possible UIP excluded), after expert panel review referral, were retrospectively analyzed from January 2016 to August 2018. Patients underwent TBCB under deep sedation with endotracheal intubation and spontaneous breathing at a single, tertiary-care, reference hospital. RESULTS: A total of 110 TBCBs (2.7 per patient, range 1 to 4) were performed. Frequent complications included mild pneumothorax in 5 patients (10%), requiring only oxygen supplementation, and bleeding in 31 patients (62%) that was mild in 19 patients and moderate in 12 patients. No serious bleeding was observed. There was zero mortality and no serious adverse events. Adequate samples for diagnostic purposes were obtained in 46 patients (92%) and pathologic histologic diagnosis was reached in 40 patients (80%). The most frequent histopathological patterns were organizing pneumonia (OP) (25%) and non-specific interstitial pneumonia (NSIP) (15%). After an expert panel review of all cases a final diagnosis was achieved in 38 patients, corresponding to a diagnostic yield of 76% for TBCB. CONCLUSION: Our single center cohort demonstrates that establishing TBCBs as a new technique is safe and feasible after proper training in specialized centers, resulting in low complication rates and adequate diagnostic yields.
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Brônquios/patologia , Criocirurgia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/patologia , Padrões de Prática Médica , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criocirurgia/efeitos adversos , Feminino , Grécia , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Fumar es la principal causa de enfermedad y de muerte evitable en todo el mundo. El consumo de tabaco está condicionado por la adicción a la nicotina, que por lo general se adquiere en la adolescencia. La irrefutable evidencia del impacto en la morbilidad y la mortalidad global demandó desarrollar estrategias para enfrentar al tabaco como el mayor problema de salud pública a nivel mundial. El Convenio Marco de Control del Tabaco (CMCT) surgió como el primer tratado internacional de salud a fines del siglo pasado, entró en vigor en 2005 con 40 países ratificantes y en la actualidad suman 181 países
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Tabagismo , Sistemas Eletrônicos de Liberação de NicotinaRESUMO
OBJECTIVES: No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This study describes treatment outcomes and complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases treated with bedaquiline-containing regimens undergoing surgery. METHODS: This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries between January 2007 and March 2015. Patients who had surgical indications in a bedaquiline-treated programme-based cohort were selected and surgery-related information was collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes. Treatment outcomes were evaluated according to the time of surgery. RESULTS: 57 bedaquiline-exposed cases resistant to a median of 7 drugs had indication for surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB). Sixty percent of cases initiated bedaquiline treatment following surgery, while 36.4% underwent the bedaquiline regimen before surgery and completed it after the operation. At treatment completion 90% culture-converted with 69.1% achieving treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8% lost to follow-up), and 9.1% were still undergoing treatment. CONCLUSIONS: The study results suggest that bedaquiline and surgery can be safely and effectively combined in selected cases with a specific indication.
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Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/cirurgiaRESUMO
BACKGROUND: A minority of European countries have participated in international comparisons with high level data on lung cancer. However, the nature and extent of data collection across the continent is simply unknown, and without accurate data collection it is not possible to compare practice and set benchmarks to which lung cancer services can aspire. METHODS: Using an established network of lung cancer specialists in 37 European countries, a survey was distributed in December 2014. The results relate to current practice in each country at the time, early 2015. The results were compiled and then verified with co-authors over the following months. RESULTS: Thirty-five completed surveys were received which describe a range of current practice for lung cancer data collection. Thirty countries have data collection at the national level, but this is not so in Albania, Bosnia-Herzegovina, Italy, Spain and Switzerland. Data collection varied from paper records with no survival analysis, to well-established electronic databases with links to census data and survival analyses. CONCLUSION: Using a network of committed clinicians, we have gathered validated comparative data reporting an observed difference in data collection mechanisms across Europe. We have identified the need to develop a well-designed dataset, whilst acknowledging what is feasible within each country, and aspiring to collect high quality data for clinical research.