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BACKGROUND: Large randomized trials have demonstrated that lung cancer (LC) screening with low-dose computed tomography (LDCT) reduces LC mortality in heavy smokers. We previously showed in the MILD screening trial that the combination of a prespecified circulating microRNA (miRNA) signature classifier (MSC) and LDCT improves the accuracy of LDCT alone. The primary aim of the prospective BioMILD study was to assess the additional value of the blood MSC assay at the time of baseline LDCT with the goal of personalizing LC screening intervals. PATIENTS AND METHODS: The study enrolled 4119 volunteers from January 2013 to March 2016, with a median follow-up of 5.3 years. Baseline LDCT and miRNAs stratified participants into four groups: CT-/MSC- (n = 2664; 64.7%); CT-/MSC+ (n = 800; 19.4%); CT+/MSC- (n = 446; 10.8%); and CT+/MSC+ (n = 209; 5.1%). As per the protocol, those in the CT-/MSC- and CT-/MSC+ groups were allocated to LDCT repeat at 3-year and 1-year intervals; CT+ participants were allocated for 1-year or earlier intervals on the basis of LDCT features independent of MSC results. RESULTS: CT+ participants had a 15.8-fold higher 4-year LC incidence than CT- participants (95% confidence interval 10.34-24.05), and MSC+ participants had a 2.0-fold higher 4-year LC incidence than MSC- participants (95% confidence interval 1.40-2.90); there was no evidence that the MSC effect differed between CT+ and CT- participants. LC incidence at 4 years was 0.8% in CT-/MSC-, 1.1% in CT-/MSC+, 10.8% in CT+/MSC-, and 20.1% in CT+/MSC+ participants. LC mortality rates at 5 years in the four risk groups were 0.5 in CT-/MSC-, 1.5 in CT-/MSC+, 4.2 in CT+/MSC-, and 10.1 in CT+/MSC+. CONCLUSION: The combined use of LDCT and blood miRNAs at baseline predicts individual LC incidence and mortality, with a major effect of MSC for LDCT-positive individuals. These findings may have important implications in personalizing screening intervals.
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Neoplasias Pulmonares , MicroRNAs , Detecção Precoce de Câncer/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Programas de Rastreamento/métodos , MicroRNAs/genética , Estudos Prospectivos , Fatores de Risco , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Combined small-cell lung cancer (C-SCLC) is composed of SCLC admixed with a non-small-cell cancer component. They currently receive the same treatment as SCLC. The recent evidence that SCLC may belong to either of two lineages, neuroendocrine (NE) or non-NE, with different vulnerability to specific cell death pathways such as ferroptosis, opens new therapeutic opportunities also for C-SCLC. MATERIALS AND METHODS: Thirteen C-SCLCs, including five with adenocarcinoma (CoADC), five with large-cell neuroendocrine carcinoma (CoLCNEC) and three with squamous cell carcinoma (CoSQC) components, were assessed for alterations in 409 genes and transcriptomic profiling of 20 815 genes. RESULTS: All 13 cases harbored TP53 (12 cases) and/or RB1 (7 cases) inactivation, which was accompanied by mutated KRAS in 4 and PTEN in 3 cases. Potentially targetable alterations included two KRAS G12C, two PIK3CA and one EGFR mutations. Comparison of C-SCLC transcriptomes with those of 57 pure histology lung cancers (17 ADCs, 20 SQCs, 11 LCNECs, 9 SCLCs) showed that CoLCNEC and CoADC constituted a standalone group of NE tumors, while CoSQC transcriptional setup was overlapping that of pure SQC. Using transcriptional signatures of NE versus non-NE SCLC as classifier, CoLCNEC was clearly NE while CoSQC was strongly non-NE and CoADC exhibited a heterogeneous phenotype. Similarly, using ferroptosis sensitivity/resistance markers, CoSQC was classified as sensitive (as expected for non-NE), CoLCNEC as resistant (as expected for NE) and CoADC showed a heterogeneous pattern. CONCLUSIONS: These data support routine molecular profiling of C-SCLC to search for targetable driver alterations and to precisely classify them according to therapeutically relevant subgroups (e.g. NE versus non-NE).
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Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/patologia , Humanos , Pulmão , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologiaRESUMO
The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.
Assuntos
Biomarcadores Tumorais/genética , Tumor Carcinoide/genética , Carcinoma de Células Grandes/genética , Neoplasias Pulmonares/genética , Carcinoma de Pequenas Células do Pulmão/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/mortalidade , Tumor Carcinoide/patologia , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/patologia , Hibridização Genômica Comparativa , Conjuntos de Dados como Assunto , Feminino , Genômica , Proteínas de Homeodomínio/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Aprendizado de Máquina , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Prognóstico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: The Multicentric Italian Lung Detection (MILD) trial demonstrated that prolonged low-dose computed tomography (LDCT) screening could achieve a 39% reduction in lung cancer (LC) mortality. We have here evaluated the long-term results of annual vs. biennial LDCT and the impact of screening intensity on overall and LC-specific mortality at 10 years. PATIENTS AND METHODS: Between 2005 and 2018, the MILD trial prospectively randomised the 2376 screening arm participants to annual (n = 1190) or biennial (n = 1186) LDCT, for a median screening period of 6.2 years and 23,083 person-years of follow-up. The primary outcomes were 10-year overall and LC-specific mortality, and the secondary end-points were the frequency of advanced-stage and interval LCs. RESULTS: The biennial LDCT arm showed a similar overall mortality (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.57-1.12) and LC-specific mortality at 10 years (HR 1.10, 95% CI 0.59-2.05), as compared with the annual LDCT arm. Biennial screening saved 44% of follow-up LDCTs in subjects with negative baseline LDCT, and 38% of LDCTs in all participants, with no increase in the occurrence of stage II-IV or interval LCs. CONCLUSIONS: The MILD trial provides original evidence that prolonged screening beyond five years with biennial LDCT can achieve an LC mortality reduction comparable to annual LDCT, in subjects with a negative baseline examination.
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Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Causas de Morte , Feminino , Humanos , Incidência , Itália/epidemiologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND: The National Lung Screening Trial showed that lung cancer (LC) screening by three annual rounds of low-dose computed tomography (LDCT) reduces LC mortality. We evaluated the benefit of prolonged LDCT screening beyond 5 years, and its impact on overall and LC specific mortality at 10 years. DESIGN: The Multicentric Italian Lung Detection (MILD) trial prospectively randomized 4099 participants, to a screening arm (n = 2376), with further randomization to annual (n = 1190) or biennial (n = 1186) LDCT for a median period of 6 years, or control arm (n = 1723) without intervention. Between 2005 and 2018, 39 293 person-years of follow-up were accumulated. The primary outcomes were 10-year overall and LC specific mortality. Landmark analysis was used to test the long-term effect of LC screening, beyond 5 years by exclusion of LCs and deaths that occurred in the first 5 years. RESULTS: The LDCT arm showed a 39% reduced risk of LC mortality at 10 years [hazard ratio (HR) 0.61; 95% confidence interval (CI) 0.39-0.95], compared with control arm, and a 20% reduction of overall mortality (HR 0.80; 95% CI 0.62-1.03). LDCT benefit improved beyond the 5th year of screening, with a 58% reduced risk of LC mortality (HR 0.42; 95% CI 0.22-0.79), and 32% reduction of overall mortality (HR 0.68; 95% CI 0.49-0.94). CONCLUSIONS: The MILD trial provides additional evidence that prolonged screening beyond 5 years can enhance the benefit of early detection and achieve a greater overall and LC mortality reduction compared with NLST trial. CLINICALTRIALS.GOV IDENTIFIER: NCT02837809.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/mortalidade , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/prevenção & controle , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/prevenção & controle , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/prevenção & controle , Taxa de SobrevidaRESUMO
The Department of Thoracic Surgery of the National Institute of Cancer in Milan developed a new rib-cage prosthesis which tries to combine flexibility, protection and bio-compatibility. This new replacement concept has been implanted in many patients, showing cheering results in term of reconstructions simplicity, postoperative complications reduction and patients comfort. This paper investigates and discusses in detail the mechanical behavior of the innovative rib cage prosthesis. Mechanical strength and stiffness are numerically evaluated in order to asses its limits and if it is fully compatible with patients 'normal' life.
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Próteses e Implantes , Costelas/fisiologia , Parede Torácica/fisiologia , Fenômenos Biomecânicos , Humanos , Modelos Biológicos , Implantação de Prótese , Estresse MecânicoAssuntos
Recidiva Local de Neoplasia/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Próteses e Implantes , Sarcoma/cirurgia , Neoplasias Torácicas/cirurgia , Adolescente , Adulto , Diafragma/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Desenho de Prótese , Procedimentos de Cirurgia Plástica/efeitos adversos , Costelas/cirurgia , Escoliose/etiologia , Parede Torácica/cirurgia , Resultado do TratamentoRESUMO
This corrects the article DOI: 10.1038/srep46479.
RESUMO
A North American trial reported a significant reduction of lung cancer mortality and overall mortality as a result of annual screening using low-dose computed tomography (LDCT). European trials prospectively tested a variety of possible screening strategies. The main topics of current discussion regarding the optimal screening strategy are pre-test selection of the high-risk population, interval length of LDCT rounds, definition of positive finding, and post-test apportioning of lung cancer risk based on LDCT findings. Despite the current lack of statistical evidence regarding mortality reduction, the European independent diverse strategies offer a multi-perspective view on screening complexity, with remarkable indications for improvements in cost-effectiveness and harm-benefit balance. The UKLS trial reported the advantage of a comprehensive and simple risk model for selection of patients with 5% risk of lung cancer in 5 years. Subjective risk prediction by biological sampling is under investigation. The MILD trial reported equal efficiency for biennial and annual screening rounds, with a significant reduction in the total number of LDCT examinations. The NELSON trial introduced volumetric quantification of nodules at baseline and volume-doubling time (VDT) for assessment of progression. Post-test risk refinement based on LDCT findings (qualitative or quantitative) is under investigation. Smoking cessation remains the most appropriate strategy for mortality reduction, and it must therefore remain an integral component of any lung cancer screening programme.
Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Programas de Rastreamento/métodos , Doses de Radiação , Tomografia Computadorizada por Raios X/métodos , Europa (Continente) , Humanos , Pulmão/diagnóstico por imagemRESUMO
INTRODUCTION: Lipomas of the gastrointestinal tract are rare, slow-growing lesions that comprise 0.4% of all gastrointestinal neoplasms. They can cause dysphagia, dyspnoea or sudden choking. CASE HISTORY: Due to rarity of this condition and its uncommon presentation, a literature review was carried out (PubMed). This search revealed 290 articles, of which 74 were considered pertinent and were evaluated. We report a case of a 13cm pedunculated oesophageal lipoma that presented with increasing dysphagia and two episodes of suffocation. The patient underwent curative resection through a cervical approach. CONCLUSIONS: Resection is recommended for large (>5 cm) or symptomatic polyps. Outcomes are excellent given that lesions are universally benign and oesophageal resection is not required.
Assuntos
Neoplasias Esofágicas , Esôfago , Lipoma , Pólipos , Idoso , Asfixia/etiologia , Transtornos de Deglutição/etiologia , Esôfago/patologia , Esôfago/fisiopatologia , Esôfago/cirurgia , Humanos , MasculinoRESUMO
OBJECTIVES: To compare the performance metrics of two different strategies of lung cancer screening by low-dose computed tomography (LDCT), namely, annual (LDCT1) or biennial (LDCT2) screen. METHODS: Recall rate, detection rate, interval cancers, sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively) were compared between LDCT1 and LDCT2 arms of the MILD trial over the first seven (T0-T6; median follow-up 7.3 years) and four rounds (T0-T3; median follow-up 7.3 years), respectively. RESULTS: 1152 LDCT1 and 1151 LDCT2 participants underwent a total of 6893 and 4715 LDCT scans, respectively. The overall recall rate was higher in LDCT2 arm (6.97 %) than in LDCT1 arm (5.81 %) (p = 0.01), which was counterbalanced by the overall lower number of LDCT scans. No difference was observed for the overall detection rate (0.56 % in both arms). The two LDCT arms had similar specificity (99.2 % in both arms), sensitivity (73.5 %, in LDCT2 vs. 68.5 % in LDCT1, p = 0.62), PPV (42.4 %, in LDCT2, vs. 40.6 %, in LDCT1, p = 0.83) and NPV (99.8 %, in LDCT2 vs. 99.7 %, in LDCT1, p = 0.71). CONCLUSION: Biennial screen may save about one third of LDCT scans with similar performance indicators as compared to annual screening. KEY POINTS: ⢠Biennial LDCT screening may be as efficient as the annual screening. ⢠Annual and biennial LDCT screening have similar frequency of interval lung cancers. ⢠Biennial screening may save about one third of LDCT scans.
Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Pulmão/diagnóstico por imagem , Programas de Rastreamento/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Curva ROC , Doses de Radiação , Fatores de TempoRESUMO
Thymic epithelial tumors (TETs) are rare primary mediastinal tumors arising from thymic epithelium. Their rarity and complexity hinder investigations of their causes and therapy development. Here, we summarize the existing knowledge regarding medical treatment of these tumors, and thoroughly review the known genetic aberrations associated with TETs and the present status of potential biological treatments. Epidermal growth factor receptor (EGFR), stem-cell factor receptor, insulin-like growth factor-1 receptor (IGF1R), and vascular endothelial growth factors (VEGF-A, VEGF-B, and VEGF-2) are overexpressed in TETs. EGFR overexpression in TETs is associated with higher stage, and IGF1R overexpression has poor prognostic value. Data indicate that anti-IGF1R monoclonal antibodies, and inhibitors of angiogenesis, somatostatin receptors, histone deacetylase, mammalian target of rapamycin, and cyclin-dependent kinases may be active against TETs. Continued investigations in this field could lead to advancement of targeted and biological therapies for TETs.
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Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Produtos Biológicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Terapia de Alvo Molecular , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Timo/tratamento farmacológico , Animais , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Produtos Biológicos/efeitos adversos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Terapia de Alvo Molecular/efeitos adversos , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias do Timo/genética , Neoplasias do Timo/metabolismo , Neoplasias do Timo/patologia , Resultado do TratamentoRESUMO
Lung cancer represents the leading cause of cancer-related death in developed countries. Despite the advances in diagnostic and therapeutic techniques, the 5-year survival rate remains low. The research for novel therapies directed to biological targets has modified the therapeutic approach, but the frequent engagement of resistance mechanisms and the substantial costs, limit the ability to reduce lung cancer mortality. MicroRNAs (miRNAs) are small noncoding RNAs with known regulatory functions in cancer initiation and progression. In this study we found that mir-660 expression is downregulated in lung tumors compared with adjacent normal tissues and in plasma samples of lung cancer patients with poor prognosis, suggesting a potential functional role of this miRNA in lung tumorigenesis. Transient and stable overexpression of mir-660 using miRNA mimics reduced migration, invasion, and proliferation properties and increased apoptosis in p53 wild-type lung cancer cells (NCI-H460, LT73, and A549). Furthermore, stable overexpression using lentiviral vectors in NCI-H460 and A549 cells inhibited tumor xenograft growth in immunodeficient mice (95 and 50% reduction compared with control, respectively), whereas the effects of mir-660 overexpression were absent in H1299, a lung cancer cell line lacking p53 locus, both in in vitro and in vivo assays. We identified and validated mouse double minute 2 (MDM2) gene, a key regulator of the expression and function of p53, as a new direct target of mir-660. In addition, mir-660 expression reduced both mRNA and protein expression of MDM2 in all cell lines and stabilized p53 protein levels resulting in an upregulation of p21(WAF1/CIP1) in p53 wild-type cells. Our finding supports that mir-660 acts as a tumor suppressor miRNA and we suggest the replacement of mir-660 as a new therapeutic approach for p53 wild-type lung cancer treatment.
Assuntos
Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Idoso , Animais , Apoptose , Carcinogênese , Proliferação de Células , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Camundongos , Camundongos SCID , MicroRNAs/genética , Pessoa de Meia-Idade , Ligação Proteica , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Surgical removal is the mainstay for early lung cancer treatment and persistent air leaks represent one of the most common clinical complications after lung surgery. Adipose tissue transplantation has been proposed as a new strategy for regenerative therapy after breast cancer surgery; however its efficacy and safety of lung tissue healing after lung resections are unknown. The purpose of this study was to test the biological activity of adipose tissue to facilitate lung tissue healing and evaluate its effect on cancer cells growth, thus providing insight for a possible clinical application. Different in vitro cellular models were used to prove the potential biologic effect of autologous fat tissue (AFT) in repairing injured lung tissue, and in vivo xenograft models were used to evaluate tumor promoting potential of AFT on putative residual cancer cells. Treatment of both embryonic (WI-38) and adult lung fibroblasts and of normal bronchial epithelial cells (HBEC-KT) with AFT samples, harvested from subcutaneous tissue layer of 20 patients undergoing pulmonary metastasectomy, improved wound healing and cell proliferation indicating a trophic effect on both mesenchymal and epithelial cell types. Conversely AFT-conditioned medium was unable to stimulate in vitro proliferation of a lung adenocarcinoma reporter cellular system (A549). Moreover, co-injection of AFT and A549 cells in nude mice did not promote engraftment and progression of A549 cells. These preclinical findings provide preliminary evidence on the potential efficacy of AFT to accelerate lung tissue repair without undesired tumor promoting effects on putative residual cancer cells.
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Adenocarcinoma/metabolismo , Proliferação de Células , Células Epiteliais/metabolismo , Fibroblastos/metabolismo , Neoplasias Pulmonares/metabolismo , Células-Tronco Neoplásicas/metabolismo , Mucosa Respiratória/metabolismo , Células-Tronco/metabolismo , Gordura Subcutânea/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Movimento Celular , Técnicas de Cocultura , Meios de Cultivo Condicionados/metabolismo , Matriz Extracelular/metabolismo , Feminino , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metastasectomia , Camundongos , Camundongos Nus , Camundongos SCID , Pessoa de Meia-Idade , Neoplasia Residual , Células-Tronco Neoplásicas/patologia , Mucosa Respiratória/citologia , Gordura Subcutânea/citologia , Gordura Subcutânea/transplante , Fatores de Tempo , Transfecção , Carga Tumoral , Cicatrização , Adulto JovemRESUMO
Ten years after the first papers on this subject, this editorial represents a brief review on lung cancer screening with low-dose spiral CT. The aim is to present the main theoretical and practical problems related to lung cancer screening, the historical background and results of observational studies and the main ongoing randomised controlled trials. In particular, the National Lung Screening Trial (NLST), which was interrupted early, is discussed. The opinion of the authors is that too many questions are still awaiting an answer.
Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Programas de Rastreamento , Tomografia Computadorizada Espiral , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: The purpose of this study was to evaluate the efficacy of a protein-based pattern in serum previously determined by MALDI-TOF-MS (Matrix Assisted Laser Desorption Ionization-Time of Flight) and considered potentially useful for prediction of clinical outcome of EGFR (epidermal growth factor receptor) TKIs (tyrosine kinase inhibitors) treated patients. DESIGN AND METHODS: We generated SELDI-TOF (Surface Enhanced Laser Desorption Ionization-Time of Flight) spectra in sera of 11 advanced NSCLC treated with Gefitinib. We detected the clusters with m/z 5843, 11445, 11529, 11685, 11759 and 11903 which were previously reported to be potential predictors of response to Gefitinib treatment. RESULTS: Four cluster peaks with m/z 5843, 11445, 11529, 11685 corresponded to SAA (serum amyloid A) protein on the basis on their calculated molecular weight, peptide fingerprinting and antibodies recognition. CONCLUSIONS: We confirm that several proteins already reported were isoforms of SAA but further studies are in development in order to evaluate the predictive value of such algorithm.
Assuntos
Proteínas Sanguíneas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Idoso , Algoritmos , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Progressão da Doença , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
We assessed the prevalence of interstitial lung disease (ILD) in a cohort of smokers included in a lung cancer screening trial. Two observers independently reviewed, for the presence of findings consistent with ILD, the computed tomography (CT) examinations of 692 heavy smokers recruited by the Multicentric Italian Lung Detection (MILD) trial. Four CT patterns were considered: usual interstitial pneumonia (UIP), other chronic interstitial pneumonia (OCIP), respiratory bronchiolitis (RB) and indeterminate. Subsequently, the evolution of ILD in those subjects who had undergone a repeat CT examination after 3 yrs was assessed. The UIP pattern and the OCIP pattern were identified in two (0.3%) out of 692 and 26 (3.8%) out of 692 patients, respectively; 109 (15.7%) out of 692 patients showed CT abnormalities consistent with RB, while an indeterminate CT pattern was reported in 21 out of 692 (3%) patients. Age, male sex and current smoking status were factors associated with the presence of OCIP and UIP (combined) pattern, although the relationship did not attain statistical significance. A progression of the disease was observed in three (25%) out of 12 subjects with OCIP who underwent repeat CT after 3 yrs. Thin-section CT features of ILD, probably representing smoking-related ILD, are not uncommon in a lung cancer screening population and should not be overlooked.
Assuntos
Bronquiolite/epidemiologia , Detecção Precoce de Câncer , Fibrose Pulmonar Idiopática/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Neoplasias Pulmonares/epidemiologia , Fumar/epidemiologia , Idoso , Bronquiolite/diagnóstico por imagem , Doença Crônica , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Itália/epidemiologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Prevalência , Radiografia , Ensaios Clínicos Controlados Aleatórios como Assunto , Testes de Função Respiratória , Estudos RetrospectivosRESUMO
Lung cancer is the primary cause of cancer mortality in developed countries. First diagnosis only when disease has already reached the metastatic phase is the main reason for failure in treatment. To this regard, although low-dose spiral computed tomography (CT) has proven to be effective in the early detection of lung cancer (providing both higher resectability and higher long-term survival rates), the capacity of annual CT screening to reduce lung cancer mortality in heavy smokers has yet to be demonstrated. Numerous ongoing large-scale randomised trials are under way in high-risk individuals with different study designs. The initial results should be available within the next 2 years.
Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Tomografia Computadorizada Espiral , Idoso , Biomarcadores Tumorais/análise , Humanos , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Tomografia Computadorizada Espiral/efeitos adversos , Tomografia Computadorizada Espiral/economiaRESUMO
The relationship between smoking, lung cancer and airflow obstruction is recognised but it is unclear whether the presence of minimal lung function damage constitutes an independent risk factor for the development of lung cancer. In order to identify those individuals at higher risk of lung cancer on the basis of functional impairment, we evaluated baseline pulmonary function tests of 3,806 heavy smokers undergoing annual chest computed tomography screening, and compared the forced expiratory volume in 1 s (FEV(1)) % predicted of 57 lung cancer cases and that of 3,749 subjects without cancer. We obtained odds ratios (ORs) of lung cancer and the corresponding 95% confidence intervals (CIs) using unconditional logistic regression, adjusting for age, sex, study and smoking variables. Compared with subjects with FEV(1) >or=90% pred, the OR of lung cancer was 2.45 (95% CI 1.39-4.33) for subjects with FEV(1) <90% pred and 2.90 (95% CI 1.34-6.27) for subjects with FEV(1) <70% pred. These data show that even a relatively small reduction in FEV(1) % pred is a significant predictor of increased lung cancer risk. Test screening for lung cancer using airflow obstruction with FEV(1) <90% is a strategy worth future consideration.