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1.
Am J Respir Crit Care Med ; 196(7): e15-e29, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28960111

RESUMO

BACKGROUND: Molecular biomarkers have the potential to improve the current state of early lung cancer detection. The goal of this project was to develop a policy statement that provides guidance about the level of evidence required to determine that a molecular biomarker, used to support early lung cancer detection, is appropriate for clinical use. METHODS: An ad hoc project steering committee was formed, to include individuals with expertise in the early detection of lung cancer and molecular biomarker development, from inside and outside of the Assembly on Thoracic Oncology. Key questions, generated from the results of a survey of the project steering committee, were discussed at an in-person meeting. Results of the discussion were summarized in a policy statement that was circulated to the steering committee and revised multiple times to achieve consensus. RESULTS: With a focus on the clinical applications of lung cancer screening and lung nodule evaluation, the policy statement outlines categories of results that should be reported in the early phases of molecular biomarker development, discusses the level of evidence that would support study of the clinical utility, describes the outcomes that should be proven to consider a molecular biomarker clinically useful, and suggests study designs capable of assessing these outcomes. CONCLUSIONS: The application of molecular biomarkers to assist with the early detection of lung cancer has the potential to substantially improve our ability to select patients for lung cancer screening, and to assist with the characterization of indeterminate lung nodules. We have described relevant considerations and have suggested standards to apply when determining whether a molecular biomarker for the early detection of lung cancer is ready for clinical use.


Assuntos
Biomarcadores Tumorais , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Humanos , Sociedades Médicas , Estados Unidos
2.
Semin Respir Crit Care Med ; 37(5): 689-707, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27732991

RESUMO

Each year, more than 1 million persons worldwide are found to have a lung nodule that carries a risk of being malignant. In reality, the vast majority of lung nodules are benign, whether identified by screening or incidentally. The consequences of delaying or missing the diagnosis of lung cancer can be substantial, as can be the consequences of invasive procedures on patients with benign lung nodules. The challenge for the clinician caring for these patients is to differentiate between benign and malignant nodules with the least harm possible. In this review, we will discuss management strategies of the indeterminate pulmonary nodule and will review recent advances and harm-reduction strategies.


Assuntos
Diagnóstico Diferencial , Neoplasias Pulmonares/diagnóstico , Nódulo Pulmonar Solitário/diagnóstico , Humanos , Achados Incidentais
3.
Int J Radiat Oncol Biol Phys ; 82(4): e631-8, 2012 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-22197235

RESUMO

PURPOSE: This study aimed to (1) examine changes in dyspnea, global pulmonary function test (PFT) results, and functional activity on ventilation (V)/perfusion (Q) single-photon emission computerized tomography (SPECT) scans during the course of radiation (RT), and (2) factors associated with the changes in patients with non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Fifty-six stage I to III NSCLC patients treated with definitive RT with or without chemotherapy were enrolled prospectively. Dyspnea was graded according to Common Terminology Criteria for Adverse Events version 3.0 prior to and weekly during RT. V/Q SPECT-computed tomography (CT) and PFTs were performed prior to and during RT at approximately 45 Gy. Functions of V and Q activities were assessed using a semiquantitative scoring of SPECT images. RESULTS: Breathing improved significantly at the third week (mean dyspnea grade, 0.8 vs. 0.6; paired t-test p = 0.011) and worsened during the later course of RT (p > 0.05). Global PFT results did not change significantly, while regional lung function on V/Q SPECT improved significantly after ∼45 Gy. The V defect score (DS) was 4.9 pre-RT versus 4.3 during RT (p = 0.01); Q DS was 4.3 pre-RT versus 4.0 during RT (p < 0.01). Improvements in V and Q functions were seen primarily in the ipsilateral lung (V DS, 1.9 pre-RT versus 1.4 during RT, p < 0.01; Q DS, 1.7 pre-RT versus 1.5 during RT, p < 0.01). Baseline primary tumor volume was significantly correlated with pre-RT V/Q DS (p < 0.01). Patients with central lung tumors had greater interval changes in V and Q than those with more peripheral tumors (p <0.05 for both V and Q DS). CONCLUSIONS: Regional ventilation and perfusion improved during RT at 45 Gy. This suggests that adaptive planning based on V/Q SPECT during RT may allow sparing of functionally recoverable lung tissue.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Dispneia/diagnóstico por imagem , Dispneia/fisiopatologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Dispneia/diagnóstico , Feminino , Volume Expiratório Forçado/fisiologia , Volume Expiratório Forçado/efeitos da radiação , Humanos , Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Estudos Prospectivos , Capacidade de Difusão Pulmonar/fisiologia , Capacidade de Difusão Pulmonar/efeitos da radiação , Dosagem Radioterapêutica , Respiração/efeitos da radiação , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Capacidade Vital/fisiologia , Capacidade Vital/efeitos da radiação
4.
Am J Clin Pathol ; 136(4): 564-71, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21917678

RESUMO

EGFR and KRAS mutation analyses are of increasing importance for guiding the treatment of non-small cell lung carcinomas. Insufficient cellularity of cell blocks can represent an impediment to the performance of these tests. We investigated the usefulness of cytologic direct smears as an alternative specimen source for mutation testing. Tumor cell-enriched areas from freshly prepared and archived rapid Romanowsky-stained direct smears in 33 cases of lung carcinoma were microdissected for DNA isolation and evaluated for EGFR and KRAS mutations. EGFR mutations were detected in 3 adenocarcinomas; 2 tumors had the L858R substitution and 1 an exon 19 deletion. KRAS mutations affecting codon 12, 13, or 61 were detected in 11 cases (8 adenocarcinomas and 3 non-small cell carcinomas). EGFR and KRAS mutations were mutually exclusive. Hence, archived and freshly prepared direct smears represent a robust and valuable specimen source for molecular studies, especially when cell blocks exhibit insufficient cellularity.


Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Análise Mutacional de DNA/métodos , DNA de Neoplasias/análise , Genes erbB-1 , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas/análise , Proteínas ras/análise , Adenocarcinoma/patologia , Sequência de Bases , Carcinoma Pulmonar de Células não Pequenas/patologia , Técnicas Citológicas , DNA de Neoplasias/genética , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Mutação , Patologia Molecular/métodos , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas p21(ras)
5.
J Thorac Oncol ; 6(1): 71-8, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21119546

RESUMO

INTRODUCTION: Perfusion (Q) single photon emission computed tomography (SPECT) has been used to divert dose away from higher-functioning lung during radiation therapy (RT) planning. This study aimed to (1) study regional lung function through coregistered pulmonary ventilation/perfusion (V/Q)-SPECT-CT and (2) classify these defects for its potential value in radiation planning in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with stages I to III NSCLC requiring radiation-based therapy were eligible for this prospective study. V/Q-SPECT performed within 2 weeks before the start of radiation was interpreted by nuclear medicine physicians and then measured by a semiquantitative score. The potential mechanism of V and Q defects was analyzed; the potential impact of V/Q-SPECT over Q-SPECT alone was completed through classified applications (high-dose RT versus RT avoidance) during planning. RESULTS: Images of 51 consecutive patients were analyzed. The V and Q defects were matched, reverse mismatched (V defect > Q defect), and mismatched (Q defect > V defect) in 61, 31, and 8% of patients, respectively. Tumor was the leading cause of the defects of ipsilateral lung in 73% of patients. The defect scores of the ipsilateral lung were greater in patients with central primaries than those with peripheral primaries for both V-SPECT (2.3 ± 1.1 versus 1.5 ± 0.8, p = 0.017) and Q-SPECT (2.2 ± 0.8 versus 1.4 ± 0.6, p = 0.000). The patients with chronic obstructive pulmonary disease had greater defect scores in contralateral lung for both V-SPECT (1.5 ± 0.7 versus 1.0 ± 0.8, p = 0.006) and Q-SPECT (1.4 ± 0.6 versus 1.0 ± 0.4, p = 0.010). On assessing the potential value of SPECT on RT plan, 39% of patients could have their RT plan when applying V/Q-SPECT rather than Q-SPECT alone. CONCLUSIONS: V/Q-SPECT provides a more comprehensive functional assessment, may provide additional value over Q-SPECT alone in assessing local pulmonary function, and guide RT plan decisions in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/classificação , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/classificação , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Prognóstico , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/radioterapia , Radiografia , Testes de Função Respiratória
6.
Int J Radiat Oncol Biol Phys ; 74(3): 790-5, 2009 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-19231108

RESUMO

PURPOSE: To determine whether time to treatment (TTT) has an effect on overall survival (OS) in patients with unresectable or medically inoperable Stage III non-small cell lung cancer (NSCLC) and whether patient or treatment factors are associated with TTT. METHODS AND MATERIALS: Included in the study were 237 consecutive patients with Stage III NSCLC treated at University of Michigan Hospital (UM) or the Veterans Affairs Ann Arbor Healthcare System (VA). Patients were treated with either palliative or definitive radiotherapy and radiotherapy alone (n = 106) or either sequential (n = 69) or concurrent chemoradiation (n = 62). The primary endpoint was OS. RESULTS: Median follow-up was 69 months, and median TTT was 57 days. On univariate analysis, the risk of death did not increase significantly with longer TTT (p = 0.093). However, subset analysis showed that there was a higher risk of death with longer TTT in patients who survived >or= 5 years (p = 0.029). Younger age (p = 0.027), male sex (p = 0.013), lower Karnofsky Performance Score (KPS) (p = 0.002), and treatment at the VA (p = 0.001) were significantly associated with longer TTT. However, on multivariate analysis, only lower KPS remained significantly associated with longer TTT (p = 0.003). CONCLUSION: Time to treatment is significantly associated with OS in patients with Stage III NSCLC who lived longer than 5 years, although it is not a significant factor in Stage III patients as a whole. Lower KPS is associated with longer TTT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/radioterapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada/métodos , Feminino , Seguimentos , Hospitais Federais , Humanos , Avaliação de Estado de Karnofsky , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Planejamento da Radioterapia Assistida por Computador , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Análise de Sobrevida , Fatores de Tempo , Estados Unidos
7.
Lung Cancer ; 59(2): 232-9, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17905467

RESUMO

BACKGROUND: This study aimed to further investigate the role of circulating TGF-beta1 during radiation therapy (RT) in predicting radiation-induced lung toxicity (RILT). METHODS AND MATERIALS: Patients with stages I-III non-small cell lung cancer treated with RT based therapy were included in this study. Platelet poor plasma was obtained pre-RT, at 2 and 4 weeks during-RT, and at the end of RT. TGF-beta1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint for RILT was >or=grade 2 radiation pneumonitis or fibrosis. RESULTS: Twenty-six patients with a minimum follow-up of 12 months were included. Six patients (23.1%) experienced >or=grade 2 RILT. There was no significant difference in absolute TGF-beta1 levels pre-RT, at 2 and 4 weeks during-RT, or at the end of RT between patients with and without RILT. The TGF-beta1 ratios (over the pre-RT levels) for patients with and without RILT at 2, 4 weeks during-, and the end of RT were 2.8+/-2.2 and 1.0+/-0.6 (P=0.123), 2.3+/-1.3 and 0.8+/-0.5 (P=0.001), 1.5+/-0.9 and 0.8+/-0.5 (P=0.098), respectively. Using 2.0 as a cut-off, the TGF-beta1 ratio at 4 weeks during-RT predicted RILT with a sensitivity and specificity of 66.7% and 95.0%, respectively. CONCLUSION: Elevation of plasma TGF-beta1 level 4 weeks during-RT is significantly predictive of RILT. The role of plasma TGF-beta1 in predicting RILT deserves further study.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/sangue , Fator de Crescimento Transformador beta1/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos
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