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Advances in the multidisciplinary care of early stage resectable NSCLC (rNSCLC) are emerging at an unprecedented pace. Numerous phase 3 trials produced results that have transformed patient outcomes for the better, yet these findings also require important modifications to the patient treatment journey trajectory and reorganization of care pathways. Perhaps, most notably, the need for multispecialty collaboration for this patient population has never been greater. These rapid advances have inevitably left us with important gaps in knowledge for which definitive answers will only become available in several years. To this end, the International Association for the Study of Lung Cancer commissioned a diverse multidisciplinary international expert panel to evaluate the current landscape and provide diagnostic, staging, and therapeutic recommendations for patients with rNSCLC, with particular emphasis on patients with American Joint Committee on Cancer-Union for International Cancer Control TNM eighth edition stages II and III disease. Using a team-based approach, we generated 19 recommendations, of which all but one achieved greater than 85% consensus among panel members. A public voting process was initiated, which successfully validated and provided qualitative nuance to our recommendations. Highlights include the following: (1) the critical importance of a multidisciplinary approach to the evaluation of patients with rNSCLC driven by shared clinical decision-making of a multispecialty team of expert providers; (2) biomarker testing for rNSCLC; (3) a preference for neoadjuvant chemoimmunotherapy for stage III rNSCLC; (4) equipoise regarding the optimal management of patients with stage II between upfront surgery followed by adjuvant therapy and neoadjuvant or perioperative strategies; and (5) the robust preference for adjuvant targeted therapy for patients with rNSCLC and sensitizing EGFR and ALK tumor alterations. Our primary goals were to provide practical recommendations sensitive to the global differences in biology and resources for patients with rNSCLC and to provide expert consensus guidance tailored to the individualized patient needs, goals, and preferences in their cancer care journey as these are areas where physicians must make daily clinical decisions in the absence of definitive data. These recommendations will continue to evolve as the treatment landscape for rNSCLC expands and more knowledge is acquired on the best therapeutic approach in specific patient and disease subgroups.
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Introduction: EGFR exon 20 insertion (ex20ins) mutations account for approximately 10% of EGFR mutations in lung adenocarcinoma. Patients with ex20ins mutation do not respond to standard EGFR tyrosine kinase inhibitor therapy. In this work, we analyzed the characteristics, treatment patterns, and outcomes in this subgroup of patients with NSCLC. Methods: The American Society of Clinical Oncology CancerLinQ Discovery data set was queried to identify patients with initial diagnosis of NSCLC between the years 1995 and 2018 and with EGFR ex20ins mutations. Data were extracted on patient demographics, tumor characteristics, treatments, and outcomes, and compared using chi-square and analysis of variance. Kaplan-Meier curves were generated to compare overall survival with log-rank tests. All analyses were performed using Python 3.6 (Python Software Foundation). Results: A total of 357 patients were eligible. Patient characteristics include a median age of 68 years comprising female sex of 54%, White race of 63%, and Black race of 9%. Approximately 62% of total patients had stage 4 disease, and 30% of all patients had brain metastasis. There were 54% of patients who were treated with chemotherapy and 15% with immune checkpoint inhibitors (ICIs). In patients with brain metastasis, 16% were treated with ICI, 18% with targeted therapy, and 59% with chemotherapy. The median survival of the entire group was 23.8 months. Among patients with stage 4 disease (n = 222): 51% were women, 64% were white, 37% had brain metastasis, 18% were treated with ICI, 14% had targeted therapy, and 60% were treated with chemotherapy. Stage 4 patients treated with targeted therapy had better survival compared with those who did not receive targeted therapy (20.6 versus 16.1 mo, p = 0.02). Univariate and multivariate analyses suggested favorable outcomes for patients treated with immunotherapy. Conclusions: EGFR ex20ins mutation represents a unique subset of NSCLC; it is associated with a higher propensity for brain metastases and a relatively modest overall survival. Novel treatment approaches are urgently needed to improve patient outcomes.
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INTRODUCTION: With global adoption of computed tomography (CT) lung cancer screening, there is increasing interest to use artificial intelligence (AI) deep learning methods to improve the clinical management process. To enable AI research using an open-source, cloud-based, globally distributed, screening CT imaging data set and computational environment that are compliant with the most stringent international privacy regulations that also protect the intellectual properties of researchers, the International Association for the Study of Lung Cancer sponsored development of the Early Lung Imaging Confederation (ELIC) resource in 2018. The objective of this report is to describe the updated capabilities of ELIC and illustrate how this resource can be used for clinically relevant AI research. METHODS: In this second phase of the initiative, metadata and screening CT scans from two time points were collected from 100 screening participants in seven countries. An automated deep learning AI lung segmentation algorithm, automated quantitative emphysema metrics, and a quantitative lung nodule volume measurement algorithm were run on these scans. RESULTS: A total of 1394 CTs were collected from 697 participants. The LAV950 quantitative emphysema metric was found to be potentially useful in distinguishing lung cancer from benign cases using a combined slice thickness more than or equal to 2.5 mm. Lung nodule volume change measurements had better sensitivity and specificity for classifying malignant from benign lung nodules when applied to solid lung nodules from high-quality CT scans. CONCLUSIONS: These initial experiments revealed that ELIC can support deep learning AI and quantitative imaging analyses on diverse and globally distributed cloud-based data sets.
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Aprendizado Profundo , Enfisema , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Inteligência Artificial , Detecção Precoce de Câncer , Pulmão/patologia , Enfisema/patologiaRESUMO
INTRODUCTION: Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is required to determine the eligibility for pembrolizumab monotherapy in advanced NSCLC worldwide and for several other indications depending on the country. Four assays have been approved/ Communauté Européene-In vitro Diagnostic (CV-IVD)-marked, but PD-L1 IHC seems diversely implemented across regions and laboratories with the application of laboratory-developed tests (LDTs). METHOD: To assess the practice of PD-L1 IHC and identify issues and disparities, the International Association for the Study of Lung Cancer Pathology Committee conducted a global survey for pathologists from January to May 2019, comprising multiple questions on preanalytical, analytical, and postanalytical conditions. RESULT: A total of 344 pathologists from 64 countries participated with 41% from Europe, 24% from North America, and 18% from Asia. Besides biopsies and resections, cellblocks were used by 75% of the participants and smears by 11%. The clone 22C3 was most often used (69%) followed by SP263 (51%). They were applied as an LDT by 40% and 30% of the users, respectively, and 76% of the participants developed at least one LDT. Half of the participants reported a turnaround time of less than or equal to 2 days, whereas 13% reported that of greater than or equal to 5 days. In addition, quality assurance (QA), formal training for scoring, and standardized reporting were not implemented by 18%, 16%, and 14% of the participants, respectively. CONCLUSIONS: Heterogeneity in PD-L1 testing is marked across regions and laboratories in terms of antibody clones, IHC assays, samples, turnaround times, and QA measures. The lack of QA, formal training, and standardized reporting stated by a considerable minority identifies a need for additional QA measures and training opportunities.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Ásia , Antígeno B7-H1 , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Europa (Continente) , Humanos , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
INTRODUCTION: Access to targeted therapies for lung cancer depends on the accurate identification of patients' biomarkers through molecular testing. The International Association for the Study of Lung Cancer (IASLC) conducted an international survey to evaluate perceptions on current practice and barriers to implementation of molecular testing. METHODS: We distributed the survey to IASLC members and other health care professionals around the world. The survey included a seven-question introduction for all respondents, who then answered according to one of three tracks: (1) requesting tests and treating patients, (2) performing and interpreting assays, or (3) tissue acquisition. Barriers to implementing molecular testing were provided in free-response fields. The chi-square test was used for regional comparisons. RESULTS: A total of 2537 respondents from 102 countries participated. Most respondents who test and treat patients believe that less than 50% of patients with lung cancer in their country receive molecular testing, but reported higher rates within their own practice. Although many results varied by region, the five most frequent barriers cited in all regions were cost, quality and standards, access, awareness, and turnaround time. Many respondents expressed dissatisfaction with the current state of molecular testing for lung cancer, including 41% of those performing and interpreting assays. Issues identified included trouble understanding results (37%) and the quality of the samples (23% reported >10% rejection rate). Despite concerns regarding the quality of testing, 47% in the performing and interpreting track stated there is no policy or strategy to improve quality in their country. In addition, 33% of respondents who request tests and treat patients were unaware of the most recent College of American Pathologists, IASLC, and Association for Molecular Pathology guidelines for molecular testing. CONCLUSIONS: Adoption of molecular testing for lung cancer is relatively low across the world. Barriers include cost, access, quality, turnaround time, and lack of awareness.
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Neoplasias Pulmonares , Quinase do Linfoma Anaplásico , Receptores ErbB/genética , Testes Genéticos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Técnicas de Diagnóstico Molecular , Inquéritos e QuestionáriosRESUMO
The global coronavirus disease 2019 pandemic continues to escalate at a rapid pace inundating medical facilities and creating substantial challenges globally. The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with cancer seems to be higher, especially as they are more likely to present with an immunocompromised condition, either from cancer itself or from the treatments they receive. A major consideration in the delivery of cancer care during the pandemic is to balance the risk of patient exposure and infection with the need to provide effective cancer treatment. Many aspects of the SARS-CoV-2 infection currently remain poorly characterized and even less is known about the course of infection in the context of a patient with cancer. As SARS-CoV-2 is highly contagious, the risk of infection directly affects the cancer patient being treated, other cancer patients in close proximity, and health care providers. Infection at any level for patients or providers can cause considerable disruption to even the most effective treatment plans. Lung cancer patients, especially those with reduced lung function and cardiopulmonary comorbidities are more likely to have increased risk and mortality from coronavirus disease 2019 as one of its common manifestations is as an acute respiratory illness. The purpose of this manuscript is to present a practical multidisciplinary and international overview to assist in treatment for lung cancer patients during this pandemic, with the caveat that evidence is lacking in many areas. It is expected that firmer recommendations can be developed as more evidence becomes available.
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Infecções por Coronavirus , Controle de Infecções/organização & administração , Neoplasias Pulmonares/terapia , Pandemias , Administração dos Cuidados ao Paciente , Pneumonia Viral , Betacoronavirus/isolamento & purificação , COVID-19 , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Humanos , Comunicação Interdisciplinar , Cooperação Internacional , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Pandemias/prevenção & controle , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/organização & administração , Administração dos Cuidados ao Paciente/tendências , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Prognóstico , SARS-CoV-2RESUMO
This Review Article provides a multi-stakeholder view on the current status of neoadjuvant therapy in lung cancer. Given the success of oncogene-targeted therapy and immunotherapy for patients with advanced lung cancer, there is a renewed interest in studying these agents in earlier disease settings with the opportunity to have an even greater impact on patient outcomes. There are unique opportunities and challenges with the neoadjuvant approach to drug development. To achieve more rapid knowledge turns, study designs, endpoints, and definitions of pathologic response should be standardized and harmonized. Continued dialogue with all stakeholders will be critical to design and test novel induction strategies, which could expedite drug development for patients with early lung cancer who are at high risk for metastatic recurrence.
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Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Terapia Neoadjuvante , Humanos , PrognósticoRESUMO
PURPOSE: To test whether a microRNA (miRNA) panel may serve as an alternative biomarker of fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor sensitivity in lung cancer. METHODS: Histologically diverse lung cancer cell lines were submitted to assays for ponatinib and AZD4547 sensitivity. miRNAs, FGFR1 messenger RNA, gene copy number, and protein expression were detected by real-time quantitative PCR, fluorescence in-situ hybridization, and immunoblotting in 34 lung cancer cell lines. RESULTS: Among 34 cell lines, 14 exhibited ponatinib sensitivity and 20 exhibited AZD4547 sensitivity (drug concentration causing 50% inhibition values < 100 nmol/L). A total of 39 of the 377-miRNA set were initially identified from the 4 paired ponatinib-sensitive or -insensitive cell lines to have at least an 8-fold differential expression and then were detected in all the 34 cell lines. A predictive panel of 3 miRNAs (let-7c, miRNA155, and miRNA218) was developed that had an area under the curve (AUC) of 0.886 with a sensitivity of 71.4% and specificity of 77.3% to predict response to ponatinib. The miRNA panel performed similar to FGFR1 protein expression (AUC = 0.864) and messenger RNA expression (AUC = 0.939), and better than FGFR1 amplification (AUC = 0.696). Furthermore, we validated this panel using data for sensitivity to AZD4547 in the cell line cohort with an AUC of 0.931 and a sensitivity of 73.3% and specificity of 76.2%, respectively. CONCLUSION: The developed miRNA panel (let-7c, miRNA155, and miRNA218) may be useful in predicting response to FGFR tyrosine kinase inhibitors, either ponatinib or AZD4547 in lung cancer cell lines, and warrants further validation in the clinical setting.
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Benzamidas/farmacologia , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Piperazinas/farmacologia , Pirazóis/farmacologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Humanos , Imidazóis/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Piridazinas/farmacologia , Transdução de Sinais , Células Tumorais CultivadasRESUMO
The isolation and analysis of circulating cell-free tumor DNA in plasma is a powerful tool with considerable potential to improve clinical outcomes across multiple cancer types, including NSCLC. Assays of this nature that use blood as opposed to tumor samples are frequently referred to as liquid biopsies. An increasing number of innovative platforms have been recently developed that improve not only the fidelity of the molecular analysis but also the number of tests performed on a single specimen. Circulating tumor DNA assays for detection of both EGFR sensitizing and resistance mutations have already entered clinical practice and many other molecular tests - such as detection of resistance mutations for Anaplastic Lymphoma Kinase (ALK) receptor tyrosine kinase rearrangements - are likely to do so in the near future. Due to an abundance of new evidence, an appraisal was warranted to review strengths and weaknesses, to describe what is already in clinical practice and what has yet to be implemented, and to highlight areas in need of further investigation. A multidisciplinary panel of experts in the field of thoracic oncology with interest and expertise in liquid biopsy and molecular pathology was convened by the International Association for the Study of Lung Cancer to evaluate current available evidence with the aim of producing a set of recommendations for the use of liquid biopsy for molecular analysis in guiding the clinical management of advanced NSCLC patients as well as identifying unmet needs. In summary, the panel concluded that liquid biopsy approaches have significant potential to improve patient care, and immediate implementation in the clinic is justified in a number of therapeutic settings relevant to NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/cirurgia , Biópsia Líquida/métodos , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologiaRESUMO
RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic interstitial lung disease characterized by (myo)fibroblast accumulation and collagen deposition. Resistance to Fas-induced apoptosis is thought to facilitate (myo)fibroblast persistence in fibrotic lung tissues by poorly understood mechanisms. OBJECTIVES: To test the hypothesis that PTPN13 (protein tyrosine phosphatase-N13) is expressed by IPF lung (myo)fibroblasts, promotes their resistance to Fas-induced apoptosis, and contributes to the development of pulmonary fibrosis. METHODS: PTPN13 was localized in lung tissues from patients with IPF and control subjects by immunohistochemical staining. Inhibition of PTPN13 function in primary IPF and normal lung (myo)fibroblasts was accomplished by: 1) downregulation with TNF-α (tumor necrosis factor-α)/IFN-γ, 2) siRNA knockdown, or 3) a cell-permeable Fas/PTPN13 interaction inhibitory peptide. The role of PTPN13 in the development of pulmonary fibrosis was assessed in mice with genetic deficiency of PTP-BL, the murine ortholog of PTPN13. MEASUREMENTS AND MAIN RESULTS: PTPN13 was constitutively expressed by (myo)fibroblasts in the fibroblastic foci of patients with IPF. Human lung (myo)fibroblasts, which are resistant to Fas-induced apoptosis, basally expressed PTPN13 in vitro. TNF-α/IFN-γ or siRNA-mediated PTPN13 downregulation and peptide-mediated inhibition of the Fas/PTPN13 interaction in human lung (myo)fibroblasts promoted Fas-induced apoptosis. Bleomycin-challenged PTP-BL-/- mice, while developing inflammatory lung injury, exhibited reduced pulmonary fibrosis compared with wild-type mice. CONCLUSIONS: These findings suggest that PTPN13 mediates the resistance of human lung (myo)fibroblasts to Fas-induced apoptosis and promotes pulmonary fibrosis in mice. Our results suggest that strategies aimed at interfering with PTPN13 expression or function may represent a novel strategy to reduce fibrosis in IPF.
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Apoptose/genética , Bleomicina/farmacologia , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/patologia , Miofibroblastos/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 13/genética , Animais , Biópsia por Agulha , Estudos de Casos e Controles , Regulação para Baixo , Resistência Microbiana a Medicamentos , Feminino , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Knockout , RNA Interferente Pequeno/genética , Valores de Referência , Técnicas de Cultura de Tecidos , Receptor fas/efeitos dos fármacosRESUMO
OBJECTIVES: The Blueprint (BP) Programmed Death Ligand 1 (PD-L1) Immunohistochemistry Comparability Project is a pivotal academic/professional society and industrial collaboration to assess the feasibility of harmonizing the clinical use of five independently developed commercial PD-L1 immunohistochemistry assays. The goal of BP phase 2 (BP2) was to validate the results obtained in BP phase 1 by using real-world clinical lung cancer samples. METHODS: BP2 were conducted using 81 lung cancer specimens of various histological and sample types, stained with all five trial-validated PD-L1 assays (22C3, 28-8, SP142, SP263, and 73-10); the slides were evaluated by an international panel of pathologists. BP2 also assessed the reliability of PD-L1 scoring by using digital images, and samples prepared for cytological examination. PD-L1 expression was assessed for percentage (tumor proportional score) of tumor cell (TC) and immune cell areas showing PD-L1 staining, with TCs scored continuously or categorically with the cutoffs used in checkpoint inhibitor trials. RESULTS: The BP2 results showed highly comparable staining by the 22C3, 28-8 and SP263 assays; less sensitivity with the SP142 assay; and higher sensitivity with the 73-10 assay to detect PD-L1 expression on TCs. Glass slide and digital image scorings were highly concordant (Pearson correlation >0.96). There was very strong reliability among pathologists in TC PD-L1 scoring with all assays (overall intraclass correlation coefficient [ICC] = 0.86-0.93), poor reliability in IC PD-L1 scoring (overall ICC = 0.18-0.19), and good agreement in assessing PD-L1 status on cytological cell block materials (ICC = 0.78-0.85). CONCLUSION: BP2 consolidates the analytical evidence for interchangeability of the 22C3, 28-8, and SP263 assays and lower sensitivity of the SP142 assay for determining tumor proportion score on TCs and demonstrates greater sensitivity of the 73-10 assay compared with that of the other assays.
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Antígeno B7-H1/imunologia , Imuno-Histoquímica/métodos , HumanosRESUMO
CONTEXT: In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. OBJECTIVE: To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update. DESIGN: The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations. RESULTS: Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline. CONCLUSIONS: The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes (ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to "rule in" targetable mutations when tissue is limited or hard to obtain.
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Adenocarcinoma , Testes Genéticos , Neoplasias Pulmonares , Seleção de Pacientes , Inibidores de Proteínas Quinases , Humanos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Quinase do Linfoma Anaplásico/genética , Consenso , Receptores ErbB/genética , Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Terapia de Alvo Molecular , Mutação , Inibidores de Proteínas Quinases/metabolismo , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proto-Oncogenes/genética , Resultado do Tratamento , Estados Unidos , Revisões Sistemáticas como AssuntoRESUMO
CONTEXT: In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. OBJECTIVE: To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update. DESIGN: The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations. RESULTS: Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline. CONCLUSIONS: The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes (ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to "rule in" targetable mutations when tissue is limited or hard to obtain.
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Neoplasias Pulmonares , Patologia Molecular , Inibidores de Proteínas Quinases , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Patologia Molecular/métodos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Estados Unidos , Revisões Sistemáticas como AssuntoRESUMO
CONTEXT: - In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. OBJECTIVE: - To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update. DESIGN: - The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations. RESULTS: - Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline. CONCLUSIONS: - The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes ( ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to "rule in" targetable mutations when tissue is limited or hard to obtain.
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Antineoplásicos , Neoplasias Pulmonares , Terapia de Alvo Molecular , Patologia Molecular , Inibidores de Proteínas Quinases , Humanos , Antineoplásicos/uso terapêutico , Testes Genéticos/métodos , Testes Genéticos/normas , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Patologia Molecular/métodos , Patologia Molecular/normas , Seleção de Pacientes , Inibidores de Proteínas Quinases/uso terapêutico , Estados Unidos , Revisões Sistemáticas como AssuntoRESUMO
Lung cancer care is rapidly changing with advances in genomic testing, the development of next-generation targeted kinase inhibitors, and the continued broad study of immunotherapy in new settings and potential combinations. The International Association for the Study of Lung Cancer and the Journal of Thoracic Oncology publish this annual update to help readers keep pace with these important developments. Experts in thoracic cancer and care provide focused updates across multiple areas, including prevention and early detection, molecular diagnostics, pathology and staging, surgery, adjuvant therapy, radiotherapy, molecular targeted therapy, and immunotherapy for NSCLC, SCLC, and mesothelioma. Quality and value of care and perspectives on the future of lung cancer research and treatment have also been included in this concise review.
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Neoplasias Torácicas , História do Século XXI , HumanosRESUMO
BACKGROUND: Access to specialty care is critical for patients with advanced stage lung cancer. This study assessed access to cancer specialists and cancer treatment in a broad population of patients with advanced stage lung cancer. MATERIALS AND METHODS: Two study samples were extracted from 2 claims databases and analyzed independently: patients aged ≥ 18 years with de novo diagnosis of metastatic lung cancer in the MarketScan database between 2008 and 2014 (commercially insured adult patients; n = 22,268); and patients aged ≥ 65 years in the Surveillance, Epidemiology, and End Results-Medicare database with a diagnosis of advanced non-small-cell lung cancer between 2007 and 2011 (Medicare-insured elderly patients; n = 9651). The study period spanned from 6 weeks before the first lung biopsy tied to the initial lung cancer diagnosis until the end of continuous health insurance enrollment, or data availability, or death. RESULTS: Among the commercially insured adults (MarketScan), most patients were seen by a cancer specialist within a month of first lung biopsy (80%), 12% were never seen by a cancer specialist, and 6% did not receive cancer-directed therapy. Among the Medicare-insured elderly patients (SEER-Medicare), the proportions were 79%, 4%, and 10%, respectively. Patients seen by a cancer specialist were more likely to receive cancer-directed therapy (95% vs. 92%, P < .001 and 92% vs. 38%, P < .001, respectively). CONCLUSION: Between 4% and 12% of patients with advanced stage lung cancer do not have appropriate access to cancer specialist, which appears to negatively affect access to optimal and timely treatment.
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Carcinoma Pulmonar de Células não Pequenas/terapia , Acessibilidade aos Serviços de Saúde , Neoplasias Pulmonares/terapia , Especialização , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Medicare , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Programa de SEER , Fatores de Tempo , Estados UnidosRESUMO
Mutations in the epidermal growth factor receptor gene (EGFR) represent one of the most frequent "actionable" alterations in non-small cell lung cancer (NSCLC). Typified by high response rates to targeted therapies, EGFR tyrosine kinase inhibitors (TKIs) are now established first-line treatment options and have transformed the treatment paradigm for NSCLC. With the recent breakthrough designation and approval of the third-generation EGFR TKI osimertinib, available systemic and local treatment options have expanded, requiring new clinical algorithms that take into account individual patient molecular and clinical profiles. In this International Association for the Study of Lung Cancer commissioned consensus statement, key pathologic, diagnostic, and therapeutic considerations, such as optimal choice of EGFR TKI and management of brain metastasis, are discussed. In addition, recommendations are made for clinical guidelines and research priorities, such as the role of repeat biopsies and use of circulating free DNA for molecular studies. With the rapid pace of progress in treating EGFR-mutant NSCLC, this statement provides a state-of-the-art review of the contemporary issues in managing this unique subgroup of patients.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Consenso , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/antagonistas & inibidores , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Lung cancer continues to be a major global health problem; the disease is diagnosed in more than 1.6 million new patients each year. However, significant progress is underway in both the prevention and treatment of lung cancer. Lung cancer therapy has now emerged as a "role model" for precision cancer medicine, with several important therapeutic breakthroughs occurring during 2015. These advances have occurred primarily in the immunotherapy field and in treatments directed against tumors harboring specific oncogenic drivers. Our knowledge about molecular mechanisms for oncogene-driven tumors and about resistance to targeted therapies has increased quickly over the past year. As a result, several regulatory approvals of new agents that significantly improve survival and quality of life for patients with lung cancer who have advanced disease have occurred. The International Association for the Study of Lung Cancer has gathered experts in different areas of lung cancer research and management to summarize the most significant scientific advancements related to prevention and therapy of lung cancer during the past year.
Assuntos
Imunoterapia , Neoplasias Pulmonares/terapia , Medicina de Precisão , Humanos , Neoplasias Pulmonares/diagnóstico , Qualidade de VidaAssuntos
Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/terapia , Animais , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Biologia Molecular , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/imunologiaRESUMO
AIM: Vote counting is frequently used in meta-analyses to rank biomarker candidates, but to our knowledge, there have been no independent assessments of its validity. Here, we used predictions from a recent meta-analysis to determine how well number of supporting studies, combined sample size and mean fold change performed as vote-counting strategy criteria. MATERIALS & METHODS: Fifty miRNAs previously ranked for their ability to distinguish lung cancer tissue from normal were assayed by RT-qPCR using 45 paired tumor-normal samples. RESULTS: Number of supporting studies predicted biomarker performance (p = 0.0006; r = 0.44), but sample size and fold change did not (p > 0.2). CONCLUSION: Despite limitations, counting the number supporting studies appears to be an effective criterion for ranking biomarkers. Predictions based on sample size and fold change provided little added value. External validation studies should be conducted to establish the performance characteristics of strategies used to rank biomarkers.