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1.
Pneumologie ; 75(9): 641-643, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34525486

RESUMO

Therapy of non-small cell lung cancer (NSCLC) should be based on biomarker test results in the palliative setting. To this end, testing of all patients in stage IV and in the future also in the earlier stages will be important. In a conference with the patronage of the German Cancer Society, the question of "reflex testing", i. e. independently of tumor stage, was discussed but not deemed to be acceptable. The current report summarizes the results of the consensus conference and discusses possible paths to efficent biomarker testing in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Biomarcadores , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Consenso , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Cuidados Paliativos
2.
BMJ Open ; 11(8): e043820, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373288

RESUMO

INTRODUCTION: Bronchoscopy is the main method in the diagnosis of various lung diseases. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the most modern bronchoscopic technique useful in diagnosis and staging of lung cancer (LC). OBJECTIVE: The aim of the study was to assess the yield of bronchoscopy in patients with suspected various respiratory diseases including LC. In particular, we examined the efficiency of different biopsy techniques in the diagnosis of LC in correlation with its localisation and pathomorphological type. PATIENTS AND METHODS: The results of pathomorphological examinations from 5279 bronchoscopies performed in 2016-2018 were analysed. The material was collected with EBUS-TBNA, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and endobronchial forceps biopsy. Clinical and demographic factors were analysed using the Fisher χ2 test. RESULTS: 5279 patients were diagnosed due to various respiratory symptoms. LC was confirmed in 36.42% of patients. 40.81% of patients had no definitive pathomorphological diagnosis. Among patients with LC, the most frequent diagnosis was non-small cell LC: squamous cell lung cancer (SCC)-32.07% and adenocarcinoma (AC)-30.61%, then small cell LC-25.83% and not otherwise specified non-small cell lung cancer (NSCLC-NOS)-11.49%. Diagnosis of SCC was obtained significantly more often (χ2=43.143, p<0.000001) by forceps biopsy (41.09%) than by EBUS-TBNA/EUS-FNA (26.62%). On the contrary, diagnosis of AC or NSCLC-NOS was significantly more often (χ2=20.394, p<0.000007, and χ2=3.902, p<0.05, respectively) observed in EBUS-TBNA/EUS-FNA (34.31% and 12.6%) than in endobronchial biopsies (24.52% and 9.64%). CONCLUSIONS: The use of bronchoscopy in the diagnosis of various lung diseases is vital but also has many limitations. Effectiveness of EBUS-TBNA and endobronchial forceps biopsy in the diagnosis of lung cancer is strongly affected by tumour localisation and type of cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Broncoscopia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos Transversais , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Mediastino/patologia , Estadiamento de Neoplasias
3.
Nat Commun ; 12(1): 5060, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417454

RESUMO

Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity for cancer detection and intervention. Here, we use a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation in a prospective study of 365 individuals at risk for lung cancer. We validate the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 lung cancer patients. Combining fragmentation features, clinical risk factors, and CEA levels, followed by CT imaging, detected 94% of patients with cancer across stages and subtypes, including 91% of stage I/II and 96% of stage III/IV, at 80% specificity. Genome-wide fragmentation profiles across ~13,000 ASCL1 transcription factor binding sites distinguished individuals with small cell lung cancer from those with non-small cell lung cancer with high accuracy (AUC = 0.98). A higher fragmentation score represented an independent prognostic indicator of survival. This approach provides a facile avenue for non-invasive detection of lung cancer.


Assuntos
DNA Tumoral Circulante/metabolismo , Fragmentação do DNA , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Diagnóstico Diferencial , Detecção Precoce de Câncer , Feminino , Genoma Humano , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Metástase Neoplásica , Estadiamento de Neoplasias , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto Jovem
4.
R I Med J (2013) ; 104(7): 36-41, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34437664

RESUMO

Lung cancer remains the most common cause of cancer-related deaths in the United States. Traditional treatment of non-small cell lung cancer has included surgical resection for suitable candidates with early stage (I/II) disease and various chemoradiotherapeutic regimens used for advanced disease, for which prognosis has been poor. Since the early 2000s, there has been a revolution in the diagnosis and treatment of non-small cell lung cancer driven by improved diagnostic techniques and therapies targeted to druggable oncogenic drivers or manipulation of the immunologic milieu in the tumor microenvironment. With this has come a need for frequently updated comprehensive data regarding response to treatment and acquired resistance to targeted therapies. In this article, we aim to provide a concise review of the state-of-the-art in lung cancer workup in 2021, with a focus on how molecular data now informs treatment decisions. With the burgeoning use of immunotherapeutic approaches, we will also discuss some of the complications seen, and briefly discuss their management.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Prognóstico , Microambiente Tumoral
5.
Se Pu ; 39(1): 77-86, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-34227361

RESUMO

Phosphorylation is one of the most important post-translational modifications in proteins. It plays a key role in numerous cellular processes, including signal transduction, cell proliferation, and intercellular communication. More than 30% of the cellular proteins are phosphorylated at a given time. However, dysregulation of phosphorylated proteins usually leads to a disorder in the intracellular signaling pathways and the onset of various diseases, especially cancer. Cell proliferation and metastasis are the major manifestations of cancer progression, and these might be affected by the protein phosphorylation levels. Clinically, cancer usually metastasizes at the middle and late stages, affecting other organs beyond primary lesion. This poses significant challenges in cancer treatment and prognosis. Consequently, comparing the phosphorylated proteomes of cells with different metastatic capabilities is helpful in studying the role of protein phosphorylation in cancer metastasis and progression. The human low metastatic lung cancer cell line 95C and high metastatic lung cancer cell line 95D are two of the four sublines isolated from human lung giant cell carcinoma cell line (PLA-801) by the single-cell cloning technique. These are ideal models for studying tumor metastasis and non-small cell lung cancer. MRC-5 cell line was obtained from a 14 week old fetal normal lung tissue. Quantitative analysis of the proteome and phosphorylated proteome in these normal lung cells and lung cancer cells with different metastatic capacities can identify key pathways and regulatory proteins associated with lung cancer metastasis and progression. Immobilized metal affinity chromatography (IMAC) is an efficient technique for the enrichment of phosphopeptides and has been widely used for phosphoproteome research. Metal ions (such as Ti4+) are immobilized on the substrate by chelation, and phosphopeptides can be selectively adsorbed under acidic conditions and eluted under alkaline conditions. IMAC can enrich phosphate groups at different amino acid sites with high specificity. In this study, Ti4+was chelated onto Ti4+-IMAC material, which was used to enrich phosphopeptides for phosphoproteome research. Two enrichment methods, namely, the vortexing method and solid phase extraction (SPE) method, were first compared for the enrichment of phosphopeptides using 10 µm Ti4+-IMAC. Phosphopeptides were highly enriched using the vortexing method. Following this, two sizes of Ti4+-IMAC material (10 µm and 30 µm) were compared to determine the efficiency of phosphopeptide enrichment. Enrichment efficiency was superior with the smaller-sized material. Therefore, the small-size Ti4+-IMAC material was selected for the proteomics research of lung cell phosphorylation. The optimized strategy was further used to compare the phosphoproteomes of the lung cancer cells with different metastatic abilities. Label-free quantification proteomics demonstrated that 510, 863, and 1108 phosphorylated proteins were identified from normal lung fibroblasts (MRC-5), low metastatic lung cancer cells (95C), and high metastatic lung cancer cells (95D), respectively, using the optimized Ti4+-IMAC method. Among them, 317 phosphorylated proteins were shared among the three groups. The protein phosphorylation level increased significantly with increasing cellular metastatic capacity. In our study, 7560 phosphorylation sites were identified on 1268 phosphorylated proteins, among which 1130 phosphorylation sites were differentially expressed. Some abnormally expressed kinases and their phosphorylation levels are closely associated with malignant cell proliferation. Comparative bioinformatics analysis showed that dysregulated phosphoproteins were mainly related to cell migration functions, such as cell invasion, migration, and death. These abnormally expressed phosphorylated proteins and phosphorylation sites could be further validated and studied for lung cancer metastasis. Our study demonstrates that Ti4+-IMAC is a powerful tool for conducting cancer metastasis-related phosphoproteome research. By optimizing the phosphopeptide enrichment strategy, our data preliminarily clarified the correlation between the abnormality of the phosphoprotein network and lung cancer metastasis. This is expected to be useful for studying phosphorylation sites, phosphorylated proteins, and their signaling pathways related to lung cancer progression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Cromatografia de Afinidade , Neoplasias Pulmonares , Proteoma , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Fosfopeptídeos , Proteoma/metabolismo
6.
Medicine (Baltimore) ; 100(27): e26528, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232188

RESUMO

ABSTRACT: It remains unknown whether dissecting the intrapulmonary lymph nodes (stations 13 and 14) when resecting peripheral non-small cell lung cancer (NSCLC) is necessary for accurate tumor node metastasis (TNM) staging. This study investigated intrapulmonary lymph node dissection (stations 13 and 14) on the pathological staging of peripheral NSCLC and the metastatic pattern of the lymph nodes.This retrospective study included patients with primary peripheral NSCLC who underwent radical dissection between January 2013 and December 2015. The clinical data of patients and examination results of intrapulmonary stations 12, 13, and 14 lymph nodes were analyzed.Of 3019 resected lymph nodes in a total of 234 patients (12.9/patient), 263 (8.7%) had metastasis. Ninety-nine patients had lymph node metastasis (42.3%): 40 (17.1%) were N1, 11 (4.7%) were N2, 48 (20.5%) were both N1 and N2, and 135 (57.7%) had no N1 or N2 metastasis. Sixteen (6.8%) patients had metastasis of stations 13 and/or 14. Metastasis in N1 positive patients of stations 10, 11, 12, 13, and 14 were 2.7%, 10.5%, 9.8%, 10.4%, and 8.5%, respectively. Missed detection without station 13 and 14 dissection was up to 6.8% (16/234).Dissection of stations 13 and 14 could be helpful for the identification of lymph node metastasis and for the accurate TNM staging of primary NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/diagnóstico , Excisão de Linfonodo/métodos , Linfonodos/diagnóstico por imagem , Estadiamento de Neoplasias , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
7.
Aging (Albany NY) ; 13(13): 17864-17879, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34257164

RESUMO

Neutrophil extracellular traps (NETs) are closely related to cancer progression. NETs-related lncRNAs play crucial roles in non-small-cell lung cancer (NSCLC) but there have been no systematic studies regarding NETs-related long noncoding RNA (lncRNA) signatures to forecast the prognosis of NSCLC patients. It's essential to build commensurate NETs-related lncRNA signatures. The expression profiles of prognostic mRNAs and lncRNAs and relevant clinical data of NSCLC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The NETs-related genes came from the results of our transcriptome RNA microarray data. The co-expression network of lncRNAs and NETs-related genes was structured to confirm NETs-related lncRNAs. The 19 lncRNAs correlated with overall survival (OS) were selected by exploiting univariate Cox regression (P < 0.05). Lasso regression and multivariate Cox regression (P < 0.05) were utilized to develop a 12-NETs-related lncRNA signature. We established a risk score based on the signature, which suggested that patients in the high-risk group displayed significantly shorter OS than patients in the low-risk group (P < 0.0001, P = 0.0023 respectively in the two cohorts). The risk score worked as an independent predictive factor for OS in both univariate and multivariate Cox regression analyses (HR> 1, P< 0.001). Additionally, by RT-qPCR, we confirmed that NSCLC cell lines have higher levels of the three adverse prognostic NETs-related lncRNAs than normal lung cells. The expression of lncRNAs significantly increases after NETs stimulation. In short, the 12 NETs-related lncRNAs and their model could play effective roles as molecular markers in predicting survival for NSCLC patients.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Espaço Extracelular/química , Armadilhas Extracelulares/química , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neutrófilos/química , Prognóstico , RNA Longo não Codificante/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biologia Computacional , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Análise de Sobrevida
8.
Lancet ; 398(10299): 535-554, 2021 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-34273294

RESUMO

Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide with an estimated 2 million new cases and 1·76 million deaths per year. Substantial improvements in our understanding of disease biology, application of predictive biomarkers, and refinements in treatment have led to remarkable progress in the past two decades and transformed outcomes for many patients. This seminar provides an overview of advances in the screening, diagnosis, and treatment of non-small-cell lung cancer and small-cell lung cancer, with a particular focus on targeted therapies and immune checkpoint inhibitors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/terapia , Humanos
9.
Lung Cancer ; 159: 34-41, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34304051

RESUMO

Non-small cell lung cancer (NSCLC) is one of the most common cancers globally and has a 5-year survival rate ~20%. Immunotherapies have demonstrated long-term and durable responses in NSCLC patients, although they appear to be effective in only a subset of patients. A more comprehensive understanding of the underlying tumour biology may contribute to identifying those patients likely to achieve optimal outcomes. Profiling the tumour microenvironment (TME) has shown to be beneficial in addressing fundamental tumour-immune cell interactions. Advances in multiplexing immunohistochemistry and molecular barcoding has led to recent advances in profiling genes and proteins in NSCLC. Here, we review the recent advancements in spatial profiling technologies for the analysis of NSCLC tissue samples to gain new insights and therapeutic options for NSCLC. The combination of spatial transcriptomics combined with advanced imaging is likely to lead to deep insights into NSCLC tissue biology, which can be a powerful tool to predict likelihood of response to therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Imuno-Histoquímica , Imunoterapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Microambiente Tumoral
10.
Lung Cancer ; 159: 45-55, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34311344

RESUMO

OBJECTIVES: We aimed to compare the prognostic value of inflammatory biomarkers extracted from pretreatment peripheral blood and [18F]-FDG PET for estimating outcomes in non-small cell lung cancer (NSCLC) patients treated with first-line immunotherapy (IT) or chemotherapy (CT). MATERIALS AND METHODS: In this retrospective multicenter study, we evaluated 111 patients with advanced NSCLC who underwent baseline [18F]-FDG PET/CT before IT or CT between 2016 and 2019. Several blood inflammatory indices were evaluated: derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP) and systemic immune-inflammation index (SII). FDG-PET inflammatory parameters were extracted from lymphoid tissues (BLR and SLR: bone marrow or spleen-to-Liver SUVmax ratios). Association with survival and relationships between parameters were evaluated using Cox prediction models and Spearman's correlation respectively. RESULTS: Overall, 90 patients were included (IT:CT) (51:39pts). Median PFS was 8.6:6.6 months and median OS was not reached:21.2 months. In the IT cohort, high dNLR (>3), high SII (≥1,270) and high SLR (0.77) were independent statistically significant prognostic factors for one-year progression-free survival (1y-PFS) and two-year overall survival (2y-OS) on multivariable analysis. In the CT cohort, high BLR (≥0.80) and high dNLR (>3) were associated with shorter 1y-PFS (HR 2.2, 95% CI 1.0-4.9) and 2y-OS (HR 3.4, 95CI 1.1-10.3) respectively, on multivariable analysis. Finally, BLR significantly but moderately correlated with most blood-based inflammatory indices (CRP, PLR and SII) while SLR was only associated with CRP (p < 0.01 for all). CONCLUSION: In advanced NSCLC patients undergoing first-line IT or CT, pretreatment blood and inflammatory factors evaluating the spleen or bone marrow on [18F]-FDG PET/CT provided prognostic information for 1y-PFS and 2y-OS. These biomarkers should be further evaluated for potential clinical application.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fluordesoxiglucose F18 , Humanos , Imunoterapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Estudos Retrospectivos
11.
Lung Cancer ; 159: 66-73, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34311346

RESUMO

OBJECTIVES: Liquid biopsy for plasma circulating tumor DNA (ctDNA) next-generation sequencing (NGS) can detect ALK fusions, though data on clinical utility of this technology in the real world is limited. MATERIALS AND METHODS: Patients with lung cancer without known oncogenic drivers or who had acquired resistance to therapy (n = 736) underwent prospective plasma ctDNA NGS. A subset of this cohort (n = 497) also had tissue NGS. We evaluated ALK fusion detection, turnaround time (TAT), plasma and tissue concordance, matching to therapy, and treatment response. RESULTS: ctDNA identified an ALK fusion in 21 patients (3%) with a variety of breakpoints and fusion partners, including EML4, CLTC, and PON1, a novel ALK fusion partner. TAT for ctDNA NGS was shorter than tissue NGS (10 vs. 20 days; p < 0.001). Among ALK fusions identified by ctDNA, 93% (13/14, 95% CI 66%-99%) were concordant with tissue evaluation. Among ALK fusions detected by tissue NGS, 54% (13/24, 95% CI 33%-74%) were concordant with plasma ctDNA. ctDNA matched patients to ALK-directed therapy with subsequent clinical response, including four patients matched on the basis of ctDNA results alone due to inadequate or delayed tissue testing. Serial ctDNA analysis detected MET amplification (n = 2) and ALK G1202R mutation (n = 2) as mechanisms of acquired resistance to ALK-directed therapy. CONCLUSION: Our findings support a complementary role for ctDNA in detection of ALK fusions and other alterations at diagnosis and therapeutic resistance settings.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias Pulmonares , Arildialquilfosfatase , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mutação , Estudos Prospectivos , Receptores Proteína Tirosina Quinases/genética
12.
Lung Cancer ; 159: 111-116, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34325317

RESUMO

OBJECTIVE: The association between the morphological characteristics and survival outcome of lung cancer associated with cystic airspaces (LCCAs) is unclear due to rarity of this disease. The current study attempted to compare the survival outcome between LCCAs and non-LCCAs and investigate the correlation between imaging features and prognosis of LCCA. METHOD: Of 10,835 patients diagnosed with non-small cell lung carcinoma (NSCLC) between January 2015 and December 2016, 123 patients with LCCA were included. The non-LCCA group comprised 3136 patients with primary solitary adenocarcinoma or squamous cell lung cancer. Propensity score matching (PSM) was performed for age, sex, tumor size, tumor stage, and lymph node involvement in a 1:1 ratio between the LCCAs and non-LCCAs, and the correlation between radiological features and recurrence-free survival (RFS) was analyzed. RESULT: The computed tomography (CT) lesion size was found to be higher in all LCCA subtypes, particularly in Type III (a cystic airspace with a mural nodule) and Type IV (mixed) LCCAs (3.09 and 3.65 cm, respectively), than in non-LCCAs (2 cm) after PSM. Three-year RFS in the LCCA group was higher than in the non-LCCA group (Type I- IV LCCAs: 100%, 84%, 77% and 83%, respectively vs. non-LCCAs: 77%). However, statistically significant difference was only found in comparison between LCCA Type I (thin-walled) and non-LCCA groups (P = 0.026). Type III lung cancer exhibited the worst survival among all four LCCA subtypes. CONCLUSIONS: The CT lesion size and pathologic tumor size varied significantly across LCCAs. Type I LCCAs exhibited better survival than non-LCCAs, whereas Type III LCCAs exhibited the worst survival rate among the four LCCA subtypes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos
13.
Lung Cancer ; 159: 117-126, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34332333

RESUMO

OBJECTIVES: Immunohistochemical expression of programmed death-ligand 1 (PD-L1) is used as a predictive biomarker for prescription of immunotherapy to non-small cell lung cancer (NSCLC) patients. Accurate assessment of PD-L1 expression is therefore crucial. In this study, the extent of interlaboratory variation in PD-L1 positivity in the Netherlands was assessed, using real-world clinical pathology data. MATERIALS AND METHODS: Data on all NSCLC patients in the Netherlands with a mention of PD-L1 testing in their pathology report from July 2017 to December 2018 were extracted from PALGA, the nationwide network and registry of histo- and cytopathology in the Netherlands. PD-L1 positivity rates were determined for each laboratory that performed PD-L1 testing, with separate analyses for histological and cytological material. Two cutoffs (1% and 50%) were used to determine PD-L1 positivity. Differences between laboratories were assessed using funnel plots with 95% confidence limits around the overall mean. RESULTS: 6,354 patients from 30 laboratories were included in the analysis of histology data. At the 1% cutoff, maximum interlaboratory variation was 39.1% (32.7%-71.8%) and ten laboratories (33.3%) differed significantly from the mean. Using the 50% cutoff, four laboratories (13.3%) differed significantly from the mean and maximum variation was 23.1% (17.2%-40.3%). In the analysis of cytology data, 1,868 patients from 23 laboratories were included. Eight laboratories (34.8%) differed significantly from the mean in the analyses of both cutoffs. Maximum variation was 41.2% (32.2%-73.4%) and 29.2% (14.7%-43.9%) using the 1% and 50% cutoffs, respectively. CONCLUSION: Considerable interlaboratory variation in PD-L1 positivity was observed. Variation was largest using the 1% cutoff. At the 50% cutoff, analysis of cytology data demonstrated a higher degree of variation than the analysis of histology data.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1 , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia
14.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207126

RESUMO

Although immune checkpoint inhibitors have changed the treatment paradigm of a variety of cancers, including non-small-cell lung cancer, not all patients respond to immunotherapy in the same way. Predictive biomarkers for patient selection are thus needed. Tumor mutation burden (TMB), defined as the total number of somatic/acquired mutations per coding area of a tumor genome (Mut/Mb), has emerged as a potential predictive biomarker of response to immune checkpoint inhibitors. We found that the limited use of TMB in clinical practice is due to the difficulty in its detection and compounded by several different biological, methodological and economic issues. The incorporation of both TMB and PD-L1 expression or other biomarkers into multivariable predictive models could result in greater predictive power.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/genética , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Mutação , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Estudos de Associação Genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Terapia de Alvo Molecular , Avaliação de Resultados da Assistência ao Paciente
15.
J Transl Med ; 19(1): 249, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34098964

RESUMO

INTRODUCTION: Programmed cell death ligand-1 (PD-L1) expression is a promising biomarker for identifying treatment related to non-small cell lung cancer (NSCLC). Automated image analysis served as an aided PD-L1 scoring tool for pathologists to reduce inter- and intrareader variability. We developed a novel automated tumor proportion scoring (TPS) algorithm, and evaluated the concordance of this image analysis algorithm with pathologist scores. METHODS: We included 230 NSCLC samples prepared and stained using the PD-L1(SP263) and PD-L1(22C3) antibodies separately. The scoring algorithm was based on regional segmentation and cellular detection. We used 30 PD-L1(SP263) slides for algorithm training and validation. RESULTS: Overall, 192 SP263 samples and 117 22C3 samples were amenable to image analysis scoring. Automated image analysis and pathologist scores were highly concordant [intraclass correlation coefficient (ICC) = 0.873 and 0.737]. Concordances at moderate and high cutoff values were better than at low cutoff values significantly. For SP263 and 22C3, the concordances in squamous cell carcinomas were better than adenocarcinomas (SP263 ICC = 0.884 vs 0.783; 22C3 ICC = 0.782 vs 0.500). In addition, our automated immune cell proportion scoring (IPS) scores achieved high positive correlation with the pathologists TPS scores. CONCLUSIONS: The novel automated image analysis scoring algorithm permitted quantitative comparison with existing PD-L1 diagnostic assays and demonstrated effectiveness by combining cellular and regional information for image algorithm training. Meanwhile, the fact that concordances vary in different subtypes of NSCLC samples, which should be considered in algorithm development.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1 , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Patologistas
16.
Artif Intell Med ; 117: 102064, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34127243

RESUMO

INTRODUCTION: Cost-effectiveness analysis (CEA) is used increasingly in medicine to determine whether the health benefit of an intervention is worth the economic cost. Decision trees, the standard decision modeling technique for non-temporal domains, can only perform CEAs for very small problems. Influence diagrams can model much larger problems, but only when the decisions are totally ordered. OBJECTIVE: To develop a CEA method for problems with unordered or partially ordered decisions, such as finding the optimal sequence of tests for diagnosing a disease. METHODS: We explain how to model those problems using decision analysis networks (DANs), a new type of probabilistic graphical model, somewhat similar to Bayesian networks and influence diagrams. We present an algorithm for evaluating DANs with two criteria, cost and effectiveness, and perform some experiments to study its computational efficiency. We illustrate the representation framework and the algorithm using a hypothetical example involving two therapies and several tests and then present a DAN for a real-world problem, the mediastinal staging of non-small cell lung cancer. RESULTS: The evaluation of a DAN with two criteria, cost and effectiveness, returns a set of intervals for the willingness to pay, separated by incremental cost-effectiveness ratios (ICERs). The cost, the effectiveness, and the optimal intervention are specific for each interval, i.e., they depend on the willingness to pay. CONCLUSION: Problems involving several unordered decisions can be modeled with DANs and evaluated in a reasonable amount of time. OpenMarkov, an open-source software tool developed by our research group, can be used to build the models and evaluate them using a graphical user interface.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Teorema de Bayes , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Análise Custo-Benefício , Humanos , Neoplasias Pulmonares/diagnóstico , Modelos Estatísticos
17.
Lung Cancer ; 158: 60-73, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34119934

RESUMO

The Middle East and Africa (MEA) region, a large geographical area, lies at the confluence of Asian, Caucasian and African races and comprises of a population with several distinct ethnicities. The course of management of non-small cell lung cancer (NSCLC) differs as per patients' performance status as well as stage of disease, requiring personalized therapy decisions. Although management of NSCLC has received a significant impetus in the form of molecularly targeted therapies and immune therapies in last few years, surgery remains gold standard for patients with early-stage disease. In case of unresectable disease, radiotherapy and chemotherapy are the primary management modalities. With newer therapies being approved for treatment of early stage disease, use of multi-disciplinary team (MDT) for comprehensive management of NSCLC is of prime importance. A group of experts with interest in thoracic oncology, deliberated and arrived at a consensus statement for the community oncologists treating patients with NSCLC in the MEA region. The deliberation was based on the review of the published evidence including literature and global and local guidelines, subject expertise of the participating panellists and experience in real-life management of patients with NSCLC. We present the proposed regional adaptations of international guidelines and recommends the MDT approach for management of NSCLC in MEA.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Oncologistas , África/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Oriente Médio/epidemiologia
18.
BMC Neurol ; 21(1): 221, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107910

RESUMO

BACKGROUND: Presentation with massive systemic embolization as the initial manifestation of occult malignancy is infrequent. The standard management of cancer-related arterial thromboembolism has not yet been established. CASE PRESENTATION: We described a case of Trousseau's syndrome resulting in acute ischemic stroke concomitant with multiple embolizations in the spleen and kidney during oral administration of dabigatran for pulmonary embolism preceding the diagnosis of a malignant tumor. A cancer-related hypercoagulable state was suspected because the patient was admitted to the neurology department due to acute ischemic stroke with three territory infarcts on diffusion-weighted imaging (DWI) in the absence of identifiable conventional risk factors and brain vessel narrowing. The patient was subsequently diagnosed with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) (stage IV) with pleural metastasis. Administration of low-molecular-weight heparin followed by long-term dabigatran under effective cancer therapy comprising gefitinib and subsequent chemotherapy did not cause stroke relapse during the 1-year follow-up. CONCLUSIONS: This case suggests that cancer-related hypercoagulability should be considered an important etiology for stroke patients who develop unexplained disseminated acute cerebral infarction without conventional stroke risk factors, especially concomitant with multiple organ embolization. Novel oral anticoagulants may be an alternative therapy for the long-term management of cancer-related arterial thromboembolism under effective cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Acidente Vascular Cerebral/etiologia , Anticoagulantes/uso terapêutico , Isquemia Encefálica/etiologia , Carcinoma Pulmonar de Células não Pequenas/complicações , Imagem de Difusão por Ressonância Magnética , Embolia/etiologia , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/complicações , Pessoa de Meia-Idade , Fatores de Risco
20.
Medicine (Baltimore) ; 100(19): e25762, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106605

RESUMO

ABSTRACT: The aim of this study was to explore the association of rs1836724 single-nucleotide polymorphism (SNP) of ERBB4 with risk and prognosis of non-small cell lung cancer (NSCLC) in the Chinese Han population.The genotype of rs1836724 SNP of ERBB4 from 258 patients with NSCLC and 200 noncancer controls were detected the TaqMan-MGB probes real-time fluorescence polymerase chain reaction. The distribution of genotype and alleles between the 2 groups was compared, and the association between clinicopathological characteristic and rs1836724 SNP was analyzed. Prognosis and influencing factors were analyzed by Kaplan-Meier and Cox regression analysis.There were significant differences in the genotype and allele distribution of ERBB4 rs1836724 between the NSCLC group and control group (P < .05). And CC genotype of rs1836724 was associated with increased risk of NSCLC in the Chinese Han population. Rs1836724 SNP was associated with TNM stage and lymph nodal metastasis (P = .001, P = .007). The median follow-up was 29 months, and the progression-free survival and overall survival of 258 NSCLC patients were 27.91% and 31.39%, respectively. Patients with GG genotype of rs1836724 had poor progression-free survival and overall survival. Rs1836724 SNP was an independent prognostic marker of NSCLC patients, CC genotype had a high risk of poor prognosis (odds ratio = 1.587, 95% confidence interval: 1.079-2.335, P = .019).In Chinese Han populations, rs1836724 SNP of ERBB4 may contribute toward the increased risk and poor prognosis of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Receptor ErbB-4/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/etnologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos de Casos e Controles , China/epidemiologia , Feminino , Seguimentos , Genótipo , Técnicas de Genotipagem , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Análise de Sobrevida
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