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1.
Rofo ; 196(2): 134-153, 2024 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-37816377

RESUMO

The process of implementing early detection of lung cancer with low-dose CT (LDCT) in Germany has gained significant momentum in recent years. It is expected that the ordinance of the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) on the early detection of lung cancer, which has been commented on by the professional societies, will come into effect by the end of 2023. Based on this regulation, the Federal Joint Committee (G-BA) will set up a program for early lung cancer detection with LDCT in the near future. In this position paper, the specialist societies involved in lung cancer screening present key points for a uniform, structured and quality-assured early detection program for lung cancer in Germany to make a constructive contribution to this process. CITATION FORMAT: · Vogel-Claussen J, Blum TG, Andreas S et al. Position paper on the implementation of a nationally organized program in Germany for the early detection of lung cancer in high-risk populations using low-dose CT screening including the management of screening findings requiring further workup. Fortschr Röntgenstr 2024; 196: DOI 10.1055/a-2178-2846.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Tomografia Computadorizada por Raios X , Neoplasias Pulmonares/diagnóstico por imagem , Fatores de Risco , Alemanha , Programas de Rastreamento
2.
Pneumologie ; 78(1): 15-34, 2024 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-37816379

RESUMO

The process of implementing early detection of lung cancer with low-dose CT (LDCT) in Germany has gained significant momentum in recent years. It is expected that the ordinance of the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) on early detection of lung cancer, which has been commented on by the professional societies, will come into effect by the end of 2023. Based on this regulation, the Federal Joint Committee (G-BA) will set up a program for early lung cancer detection with LDCT in the near future. In this position paper, the specialist societies involved in lung cancer screening present concrete cornerstones for a uniform, structured and quality-assured early detection program for lung cancer in Germany to make a constructive contribution to this process.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Tomografia Computadorizada por Raios X , Neoplasias Pulmonares/diagnóstico por imagem , Fatores de Risco , Alemanha , Programas de Rastreamento
3.
Zentralbl Chir ; 149(1): 96-115, 2024 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-37816386

RESUMO

The process of implementing early detection of lung cancer with low-dose CT (LDCT) in Germany has gained significant momentum in recent years. It is expected that the ordinance of the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) on early detection of lung cancer, which has been commented on by the professional societies, will come into effect by the end of 2023. Based on this regulation, the Federal Joint Committee (G-BA) will set up a program for early lung cancer detection with LDCT in the near future. In this position paper, the specialist societies involved in lung cancer screening present concrete cornerstones for a uniform, structured and quality-assured early detection program for lung cancer in Germany to make a constructive contribution to this process.

4.
Pneumologie ; 77(10): 671-813, 2023 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-37884003

RESUMO

The current S3 Lung Cancer Guidelines are edited with fundamental changes to the previous edition based on the dynamic influx of information to this field:The recommendations include de novo a mandatory case presentation for all patients with lung cancer in a multidisciplinary tumor board before initiation of treatment, furthermore CT-Screening for asymptomatic patients at risk (after federal approval), recommendations for incidental lung nodule management , molecular testing of all NSCLC independent of subtypes, EGFR-mutations in resectable early stage lung cancer in relapsed or recurrent disease, adjuvant TKI-therapy in the presence of common EGFR-mutations, adjuvant consolidation treatment with checkpoint inhibitors in resected lung cancer with PD-L1 ≥ 50%, obligatory evaluation of PD-L1-status, consolidation treatment with checkpoint inhibition after radiochemotherapy in patients with PD-L1-pos. tumor, adjuvant consolidation treatment with checkpoint inhibition in patients withPD-L1 ≥ 50% stage IIIA and treatment options in PD-L1 ≥ 50% tumors independent of PD-L1status and targeted therapy and treatment option immune chemotherapy in first line SCLC patients.Based on the current dynamic status of information in this field and the turnaround time required to implement new options, a transformation to a "living guideline" was proposed.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/prevenção & controle , Antígeno B7-H1/genética , Antígeno B7-H1/uso terapêutico , Seguimentos , Receptores ErbB/genética , Carcinoma Pulmonar de Células não Pequenas/patologia
5.
Int J Mol Sci ; 24(13)2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37445733

RESUMO

Pulmonary sarcomatoid carcinoma (PSC) has highly aggressive biological behaviour and poor clinical outcomes, raising expectations for new therapeutic strategies. We characterized 179 PSC by immunohistochemistry, next-generation sequencing and in silico analysis using a deep learning algorithm with respect to clinical, immunological and molecular features. PSC was more common in men, older ages and smokers. Surgery was an independent factor (p < 0.01) of overall survival (OS). PD-L1 expression was detected in 82.1% of all patients. PSC patients displaying altered epitopes due to processing mutations showed another PD-L1-independent immune escape mechanism, which also significantly influenced OS (p < 0.02). The effect was also maintained when only advanced tumour stages were considered (p < 0.01). These patients also showed improved survival with a significant correlation for immunotherapy (p < 0.05) when few or no processing mutations were detected, although this should be interpreted with caution due to the small number of patients studied. Genomic alterations for which there are already approved drugs were present in 35.4% of patients. Met exon 14 skipping was found more frequently (13.7%) and EGFR mutations less frequently (1.7%) than in other NSCLC. In summary, in addition to the divergent genomic landscape of PSC, the specific immunological features of this prognostically poor subtype should be considered in therapy stratification.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma , Neoplasias Pulmonares , Masculino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/metabolismo , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Mutação
7.
Eur Respir J ; 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37202154

RESUMO

Screening for lung cancer with low radiation dose computed tomography (LDCT) has a strong evidence base. The European Council adopted a recommendation in November 2022 that lung cancer screening be implemented using a stepwise approach. The imperative now is to ensure that implementation follows an evidence-based process that delivers clinical and cost effectiveness. This ERS Taskforce was formed to provide a technical standard for a high-quality lung cancer screening program. METHOD: A collaborative group was convened to include members of multiple European societies (see below). Topics were identified during a scoping review and a systematic review of the literature was conducted. Full text was provided to members of the group for each topic. The final document was approved by all members and the ERS Scientific Advisory Committee. RESULTS: Ten topics were identified representing key components of a screening program. The action on findings from the LDCT were not included as they are addressed by separate international guidelines (nodule management and clinical management of lung cancer) and by a linked taskforce (incidental findings). Other than smoking cessation, other interventions that are not part of the core screening process were not included (e.g. pulmonary function measurement). Fifty-three statements were produced and areas for further research identified. CONCLUSION: This European collaborative group has produced a technical standard that is a timely contribution to implementation of LCS. It will serve as a standard that can be used, as recommended by the European Council, to ensure a high quality and effective program.

8.
Lung Cancer ; 179: 107184, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37040677

RESUMO

INTRODUCTION: Checkpoint-inhibitor pneumonitis (CIP) represents a major immune-related adverse event (irAE) in patients with lung cancer. We aimed for the clinical characterization, diagnostics, risk factors, treatment and outcome in a large cohort of patients from everyday clinical practice. PATIENTS AND METHODS: For this retrospective analysis, 1,376 patients having received checkpoint inhibitors (CPI) in any line of therapy from June 2015 until February 2020 from three large-volume lung cancer centers in Berlin, Germany were included and analyzed. RESULTS: With a median follow-up of 35 months, all-grade, high-grade (CTCAE ≥ 3) and fatal CIP were observed in 83 (6.0%), 37 (2.7%) and 12 (0.9%) patients, respectively, with a median onset 4 months after initiation of CPI therapy. The most common radiologic patterns were organizing pneumonia (OP) and non-specific interstitial pneumonia (NSIP) (37% and 31%). All except 7 patients with G1-2 CIP interrupted treatment. Corticosteroids were administered to 74 patients with a median starting dose of 0.75 mg/kg. After complete restitution (n = 67), re-exposure to CPI (n = 14) led to additional irAE in 43% of the cases. Thoracic radiotherapy targeting the lung was the only independent risk factor for CIP (odds ratio 2.8, p < 0.001) and pretherapeutic diffusing capacity for carbon monoxide inversely correlated with CIP severity. Compared with patients without CIP and non-CIP irAE, CIP was associated with impaired overall survival (hazard ratios 1.23, p = 0.24 and 2.01, p = 0.005). CONCLUSIONS: High-grade CIP accounts for almost half of all CIP cases in an allcomer lung cancer population. A continuous vigilance, rapid diagnostics and adequate treatment are key to prevent disease progression associated with impaired survival.


Assuntos
Neoplasias Pulmonares , Pneumonia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Pneumonia/etiologia , Fatores de Risco , Gestão de Riscos
9.
Pneumologie ; 77(3): 143-157, 2023 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-36918016

RESUMO

The SARS-CoV-2 pandemic had a tremendous impact on diagnosis and treatment of interstitial lung diseases (ILD). Especially in the early phase of the pandemic, when the delta variant was prevailling, a huge number of viral pneumonias were observed, which worsened pre-existing, triggered de novo occurence or discovery of previously subclincal interstitial lung diseases. The effect of SARS-CoV-2 infection - without or with accompanying viral pneumonia - on the further development of pre-existing ILD as well of new pulmonary inflitrates and consolidiations is difficult to predict and poses a daily challenge to interdisciplinary ILD boards. This position paper of the German Respiratory Society (DGP e.V.) provides answers to the most pressing questions based on current knowledge.


Assuntos
COVID-19 , Doenças Pulmonares Intersticiais , Pneumonia Viral , Humanos , SARS-CoV-2 , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/terapia , Pulmão , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia
10.
Eur Respir J ; 61(2)2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36396145

RESUMO

This European Respiratory Society guideline is dedicated to the provision of good quality recommendations in lung cancer care. All the clinical recommendations contained were based on a comprehensive systematic review and evidence syntheses based on eight PICO (Patients, Intervention, Comparison, Outcomes) questions. The evidence was appraised in compliance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence profiles and the GRADE Evidence to Decision frameworks were used to summarise results and to make the decision-making process transparent. A multidisciplinary Task Force panel of lung cancer experts formulated and consented the clinical recommendations following thorough discussions of the systematic review results. In particular, we have made recommendations relating to the following quality improvement measures deemed applicable to routine lung cancer care: 1) avoidance of delay in the diagnostic and therapeutic period, 2) integration of multidisciplinary teams and multidisciplinary consultations, 3) implementation of and adherence to lung cancer guidelines, 4) benefit of higher institutional/individual volume and advanced specialisation in lung cancer surgery and other procedures, 5) need for pathological confirmation of lesions in patients with pulmonary lesions and suspected lung cancer, and histological subtyping and molecular characterisation for actionable targets or response to treatment of confirmed lung cancers, 6) added value of early integration of palliative care teams or specialists, 7) advantage of integrating specific quality improvement measures, and 8) benefit of using patient decision tools. These recommendations should be reconsidered and updated, as appropriate, as new evidence becomes available.


Assuntos
Neoplasias Pulmonares , Pulmão , Humanos , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Tórax , Sociedades Médicas
11.
Int J Mol Sci ; 23(20)2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36293366

RESUMO

Precision oncology and immunotherapy have revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC). Emerging studies show that targeted therapies are also beneficial for patients with driver alterations such as epidermal growth factor receptor (EGFR) mutations in early-stage NSCLC (stages I-IIIA). Furthermore, patients with elevated programmed death-ligand 1 (PD-L1) expression appear to respond favorably to adjuvant immunotherapy. To determine the frequency of genomic alterations and PD-L1 status in early-stage NSCLC, we retrospectively analyzed data from 2066 unselected, single-center patients with NSCLC diagnosed using next-generation sequencing and immunohistochemistry. Nine-hundred and sixty-two patients (46.9%) presented with early-stage NSCLC. Of these, 37.0% had genomic alterations for which targeted therapies have already been approved for advanced NSCLC. The frequencies of driver mutations in the early stages were equivalent to those in advanced stages, i.e., the rates of EGFR mutations in adenocarcinomas were 12.7% (72/567) and 12.0% (78/650) in early and advanced NSCLC, respectively (p = 0778). In addition, 46.3% of early-stage NSCLC cases were PD-L1-positive, with a tumor proportion score (TPS) of ≥1%. With comparable frequencies of driver mutations in early and advanced NSCLC and PD-L1 overexpression in nearly half of patients with early-stage NSCLC, a broad spectrum of biomarkers for adjuvant and neoadjuvant therapies is available, and several are currently being investigated in clinical trials.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Medicina de Precisão , Receptores ErbB/genética , Genômica , Mutação
12.
Respiration ; 101(3): 307-320, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35231915

RESUMO

Assessing the risk for specific patient groups to suffer from severe courses of COVID-19 is of major importance in the current SARS-CoV-2 pandemic. This review focusses on the risk for specific patient groups with chronic respiratory conditions, such as patients with asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF), sarcoidosis, interstitial lung diseases, lung cancer, sleep apnea, tuberculosis, neuromuscular diseases, a history of pulmonary embolism, and patients with lung transplants. Evidence and recommendations are detailed in exemplary cases. While some patient groups with chronic respiratory conditions have an increased risk for severe courses of COVID-19, an increasing number of studies confirm that asthma is not a risk factor for severe COVID-19. However, other risk factors such as higher age, obesity, male gender, diabetes, cardiovascular diseases, chronic kidney or liver disease, cerebrovascular and neurological disease, and various immunodeficiencies or treatments with immunosuppressants need to be taken into account when assessing the risk for severe COVID-19 in patients with chronic respiratory diseases.


Assuntos
COVID-19 , Médicos , Humanos , Masculino , Pandemias , Medição de Risco , SARS-CoV-2
13.
J Clin Oncol ; 39(25): 2791-2802, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34077268

RESUMO

PURPOSE: Although NRG1 fusions are oncogenic drivers across multiple tumor types including lung cancers, these are difficult to study because of their rarity. The global eNRGy1 registry was thus established to characterize NRG1 fusion-positive lung cancers in the largest and most diverse series to date. METHODS: From June 2018 to February 2020, a consortium of 22 centers from nine countries in Europe, Asia, and the United States contributed data from patients with pathologically confirmed NRG1 fusion-positive lung cancers. Profiling included DNA-based and/or RNA-based next-generation sequencing and fluorescence in situ hybridization. Anonymized clinical, pathologic, molecular, and response (RECIST v1.1) data were centrally curated and analyzed. RESULTS: Although the typified never smoking (57%), mucinous adenocarcinoma (57%), and nonmetastatic (71%) phenotype predominated in 110 patients with NRG1 fusion-positive lung cancer, further diversity, including in smoking history (43%) and histology (43% nonmucinous and 6% nonadenocarcinoma), was elucidated. RNA-based testing identified most fusions (74%). Molecularly, six (of 18) novel 5' partners, 20 unique epidermal growth factor domain-inclusive chimeric events, and heterogeneous 5'/3' breakpoints were found. Platinum-doublet and taxane-based (post-platinum-doublet) chemotherapy achieved low objective response rates (ORRs 13% and 14%, respectively) and modest progression-free survival medians (PFS 5.8 and 4.0 months, respectively). Consistent with a low programmed death ligand-1 expressing (28%) and low tumor mutational burden (median: 0.9 mutations/megabase) immunophenotype, the activity of chemoimmunotherapy and single-agent immunotherapy was poor (ORR 0%/PFS 3.3 months and ORR 20%/PFS 3.6 months, respectively). Afatinib achieved an ORR of 25%, not contingent on fusion type, and a 2.8-month median PFS. CONCLUSION: NRG1 fusion-positive lung cancers were molecularly, pathologically, and clinically more heterogeneous than previously recognized. The activity of cytotoxic, immune, and targeted therapies was disappointing. Further research examining NRG1-rearranged tumor biology is needed to develop new therapeutic strategies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Imunoterapia/mortalidade , Neoplasias Pulmonares/patologia , Neuregulina-1/genética , Proteínas de Fusão Oncogênica/genética , Sistema de Registros/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos/epidemiologia
14.
Lung Cancer ; 151: 44-52, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33307417

RESUMO

The majority of research within lung cancer is focused on prevention, diagnosis and treatment rather than examining infrastructure or processes of lung cancer centres. Benchmarking is a systematic method for documenting and comparing processes, functions or performance of organisations against the best in the world. ADVANCE-1 is a European Respiratory Society funded pilot study with the main aim of creating a benchmarking tool that can easily document and reflect the structure and process within a lung cancer centre and its associated registry. By doing this we can then compare centres and generate best practice learning points from each centre in order to learn from each other. The ADVANCE-1 study group was constituted by two ERS fellowship-holders and senior lung cancer specialists from the two participating lung cancer services in Glasgow, Scotland, and Berlin, Germany. The study design and benchmarking tools were reviewed externally. Once the benchmarking tools were created, prospective testing was undertaken in the two participating centres in order to allow comparison to ascertain best practice in a so called 'collaborative benchmarking approach'. We were then able to create personalised learning points for each centre. The next phase of the project will be to expand the benchmarking across several European centres in the ADANCE-2 project.


Assuntos
Benchmarking , Neoplasias Pulmonares , Alemanha , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Projetos Piloto , Estudos Prospectivos , Escócia
15.
ERJ Open Res ; 6(2)2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32714955

RESUMO

Lung cancer is a devastating disease affecting hundreds of thousands of patients in Europe. Despite recent advances in treatment, its prognosis remains poor. This is mainly attributed to the late stages that diagnoses are usually established at, consequently excluding curative treatment options. During the 2019 European Respiratory Society International Congress in Madrid, Spain, lung cancer experts presented the most recent aspects of lung cancer early detection with low-dose computed tomography.

16.
Eur Respir J ; 55(2)2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32051182

RESUMO

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.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Análise Custo-Benefício , Europa (Continente) , Humanos , Neoplasias Pulmonares/diagnóstico , Sistema de Registros
17.
Eur Radiol ; 30(6): 3277-3294, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32052170

RESUMO

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.


Assuntos
Consenso , Tomada de Decisões , Neoplasias Pulmonares/diagnóstico , Detecção Precoce de Câncer/métodos , Europa (Continente) , Humanos , Sistema de Registros
18.
J Thorac Dis ; 12(12): 7571-7590, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33447448

RESUMO

Thymomas are counted among the rare tumour entities which are associated with autoimmune disorders (AIDs) and paraneoplastic syndromes (PNS) far more often than other malignancies. Through its complex immunological function in the context of the selection and maturation of T cells, the thymus is at the same time highly susceptible to disruptive factors caused by the development and growth of thymic tumours. These T cells, which are thought to develop to competent immune cells in the thymus, can instead adopt autoreactive behaviour due to the uncontrolled interplay of thymomas and become the trigger for AID or PNS affecting numerous organs and tissues within the human body. While myasthenia gravis is the most prevalent PNS in thymoma, numerous others have been described, be they related to neurological, cardiovascular, gastrointestinal, haematological, dermatological, endocrine or systemic disorders. This review article sheds light on the pathophysiology, epidemiology, specific clinical features and therapeutic options of the various forms as well as courses and outcomes of AID/PNS in association with thymomas. Whenever suitable and backed by the limited available evidence, the perspectives from both the thymoma and the affected organ/tissue will be highlighted. Specific issues addressed are the prognostic significance of thymectomy on myasthenia gravis and other thymoma-associated AID/PND and further the impact and safety of immunotherapies on AID and PND relating to thymomas.

19.
Oncotarget ; 10(55): 5690-5702, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31620244

RESUMO

The analysis of circulating cell-free DNA (cfDNA) extracted from peripheral blood can serve as a minimally invasive alternative to tumor tissue biopsies in cases with impaired access to tissue. Its clinical utility has been well demonstrated for EGFR T790M testing in lung cancer patients suffering progress after tyrosine kinase inhibitor treatment. At present, highly sensitive unique molecular identifiers (UMI)-based NGS for liquid biopsy testing is less established compared to single gene assays. However, the critical bottleneck are sufficient cfDNA yields, which are essentially required to obtain meaningful test results. We compared four different cfDNA extraction methods (Qiagen, Promega, Thermo and Stratec) using the same plasma samples in order to evaluate their suitability for further NGS analysis. We managed to draw 60 ml blood from 12 patients each and equally collected 30ml in PAXgene and EDTA tubes at the same time point, sufficient for total of 96 cfDNA extractions. CfDNA concentrations and total amounts were highest for Qiagen and Promega protocols, showing the best read length profiles after sequencing. Known oncogenic driver mutations were identified in 9 out of 12 patients with at least one of the cfDNA extraction methods, again favoring the extraction protocols from Qiagen and Promega. We also uncovered putative sequencing artefacts including known driver genes pointing to a careful consideration for the limit of detection of this methodology. Our study shows that pre-analytical optimization is necessary to achieve the maximum sensitivity of UMI-based sequencing but also highlights the low abundance of tumor-derived cfDNA in lung cancer samples.

20.
ERJ Open Res ; 5(2)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31218220

RESUMO

Lung cancer is a substantial global burden for patients, healthcare professionals and healthcare systems. Multiple scientific international and national initiatives are tackling the various problems associated with this disease, which is currently the leading cause of cancer-related mortality worldwide. During the European Respiratory Society International Congress 2018 in Paris, France, lung cancer experts gathered to present the most recent aspects of lung cancer care, and discuss the need for joint initiatives and an international lung cancer alliance, aiming to provide high quality, accessible health care. The US experience and American Lung Association/American Thoracic Society implementation guide on lung cancer screening programmes, the key features of optimising and implementing such programmes, the challenges of treatment in the subset of patients where lung cancer is combined with interstitial lung disease, and novel lung cancer biomarkers and immunotherapy were among the most anticipated issues covered during the congress.

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