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1.
Trials ; 22(1): 168, 2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33639999

RESUMO

BACKGROUND: Invasive mediastinal nodal staging is recommended by guidelines in selected patients with resectable non-small cell lung cancer (NSCLC). Endosonography is recommended as initial staging technique, followed by confirmatory mediastinoscopy in case of negative N2 or N3 cytology after endosonography. Confirmatory mediastinoscopy however is under debate owing its limited additional diagnostic value, its associated morbidity and its delay in the start of lung cancer treatment. The MEDIASTrial examines whether confirmatory mediastinoscopy can be safely omitted after negative endosonography in mediastinal nodal staging of NSCLC. The present work is the proposed statistical analysis plan of the clinical consequences of omitting mediastinoscopy, which is submitted before closure of the MEDIASTrial and before knowledge of any results was done to enhance transparency of scientific behaviour. METHODS: The primary outcome measure of this non-inferiority trial will be unforeseen N2 disease resulting from lobe-specific mediastinal lymph node dissection. For non-inferiority, the upper limit of the 95% confidence interval of the unforeseen N2 rate in the group without mediastinoscopy should not exceed 14.3% in order to probably have no negative impact on survival. Since this is a non-inferiority trial, both an intention to treat (ITT) and a per protocol (PP) analyses will be done. The ITT and the PP analyses should both indicate non-inferiority before the diagnostic strategy omitting mediastinoscopy will be interpreted as non-inferior to the strategy with mediastinoscopy. Secondary outcome measures include 30-day major morbidity and mortality, the total number of days of hospital care, overall and disease free 2-year survival, generic and disease-specific health related quality of life and cost-effectiveness and cost-utility of staging strategies with and without mediastinoscopy. DISCUSSION: The MEDIASTrial will determine if confirmatory mediastinoscopy can be omitted after tumour negative systematic endosonography in invasive mediastinal staging of patients with resectable NSCLC. TRIAL REGISTRATION: Netherlands Trial Register NL6344/NTR6528 . Registered on 2017 July 06.

3.
Lung Cancer ; 150: 186-194, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33189983

RESUMO

OBJECTIVES: Lymph node staging in patients with non-small cell lung cancer is crucial for determining prognosis and treatment. Our objective was to evaluate the clinical- to pathological agreement of guideline-concordant nodal staging in patients with resectable NSCLC and assess occurrence and distribution of occult lymph node metastases (OLM). MATERIALS AND METHODS: In a retrospective single center cohort study (n = 390), we analyzed all surgically treated NSCLC patients from January 2015 until April 2019. Patients were classified into sub-groups (1) mediastinal staging by PET-CT/CT-scan (IMAGE-group) or (2) invasive staging by endobronchial ultrasound and mediastinoscopy (INVAS-group). Agreement between final clinical (cN) and pathological nodal stage (pN) and the presence and location of OLM are analyzed. RESULTS: Agreement between cN- and pN-stage was 86.3 % in the IMAGE-group (n = 117) and 50.9 % in the INVAS-group (n = 167). Occult N1 disease was found in 33 patients (16.6 % in cN0) of which 52 % occurred in LN-regions 12-14. Occult N2 disease was found in 20 cases (6.5 % in cN0 and 12.7 % in cN1). Combined, 23.1 % of all pre-operatively cN0-staged patients (n = 46/199) had OLM (pN+), of which 12.1 % (24/199) had metastases in regions 5-6 and/or 12-14. Of all patients with OLM, 50.0 % (23/46) had primary tumors ≤30 mm. CONCLUSION: OLM are frequently identified in clinically N0/N1 NSCLC, also in tumors <3 cm, and often in regions beyond reach of current staging techniques. These findings should be addressed when non-surgical treatment or sub-lobar resections are considered for early stage lung cancer.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32649327

RESUMO

BACKGROUND: Bronchoscopic diagnosis of small peripheral lung lesions suspected of lung cancer remains a challenge. A successful endobronchial diagnosis comprises navigation, confirmation, and tissue acquisition. In all steps, 3-dimensional information is essential. Cone-beam computed tomography (CBCT) imaging can provide computed tomography information and 3-dimensional augmented fluoroscopy imaging. We assessed whether CBCT imaging can improve navigation and diagnosis of peripheral lesions by 2 clinical workflows with a cross-over design: (1) a primary CBCT and radial endobronchial ultrasound mini probe imaging-based approach and (2) a primary electromagnetic navigation (EMN) and radial endobronchial ultrasound mini probe imaging-based approach. METHODS: All patients with a peripheral lung lesion biopsy indication were eligible for study inclusion and randomly assigned to study arms. Commercially available equipment was used. The main study goals were to assess CBCT-confirmed navigation success and diagnostic accuracy. Surgery or unambiguous clinical follow-up served as the gold standard. RESULTS: Eighty-seven patients with 107 lesions were included. Lesion mean longest axis size in the CBCT arm was 16.6 mm (n=47) and 14.2 mm in the EMN arm (n=40). The primary CBCT approach and primary EMN approach had 76.3% and 52.2% navigation success, respectively. Addition of EMN to the CBCT approach increased navigation success to 89.9%. Addition of CBCT imaging to the EMN approach significantly increased navigation success to 87.5% per lesion. The overall diagnostic accuracy per patient was significantly lower than the navigation success, being 72.4%. CONCLUSION: CBCT imaging is a valuable addition to navigation bronchoscopy. Although overall navigation success was high, the diagnostic accuracy remains to be improved. Future research should focus on improving the tissue acquisition methodology.

6.
Respiration ; 99(6): 484-492, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492682

RESUMO

BACKGROUND: Systematic assessment of lymph node status by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is indicated in (suspected) lung cancer. Sampling is herein guided by nodal size and FDG-PET characteristics. Ultrasound strain elastography (SE) might further improve risk stratification. By imaging tissue deformation over time, SE computes relative tissue strain. In several tissues, a lower strain (deformation) has been associated with a higher likelihood of malignancy. OBJECTIVES: To assess if EBUS-SE can independently help predict malignancy, and when combined with size and FDG uptake information. METHODS: This multicenter (n = 5 centers) prospective trial included patients with suspected or proven lung cancer using a standardized measurement protocol. Cytopathology combined with surgery or follow-up imaging (>6 months) were used as reference standard. RESULTS: Between June 2016 and July 2018, 327 patients and 525 lymph nodes were included (mean size 12.3 mm, malignancy prevalence 0.48). EBUS-SE had an overall AUC of 0.77. A mean strain <115 (range 0-255) showed 90% sensitivity, 43% specificity, 60% positive predictive value, and 82% negative predictive value. Combining EBUS-SE (<115) with size (<8 mm) and FDG-PET information into a risk stratification algorithm increased the accuracy. Combining size and SE showed that the 48% a priori chance of malignancy changed to 11 and 70% in double negative or positive nodes, respectively. In the subset where FDG-PET was available (n = 370), triple negative and positive nodes went from a 42% a priori chance of malignancy to 9 and 73%, respectively. CONCLUSIONS: EBUS-SE can help predict lymph node malignancy and may be useful for risk stratification when combined with size and PET information.

7.
Br J Cancer ; 121(5): 372-377, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31337877

RESUMO

BACKGROUND: Retrospective studies suggest that low molecular weight heparin may delay the development of metastasis in patients with resected NSCLC. METHODS: Multicentre phase 3 study with patients with completely resected NSCLC who were randomised after surgery to receive chemotherapy with or without nadroparin. The main exclusion criteria were R1/2 and wedge/segmental resection. FDG-PET was required. The primary endpoint was recurrence-free survival (RFS). RESULTS: Among 235 registered patients, 202 were randomised (nadroparin: n = 100; control n = 102). Slow accrual enabled a decrease in the number of patients needed from 600 to 202, providing 80% power to compare RFS with 94 events (α = 0.05; 2-sided). There were no differences in bleeding events between the two groups. The median RFS was 65.2 months (95% CI, 36-NA) in the nadroparin arm and 37.7 months (95% CI, 22.7-NA) in the control arm (HR 0.77 (95% CI, 0.53-1.13, P = 0.19). FDG-PET SUVmax ≥10 predicted a greater likelihood of recurrence in the first year (HR 0.48, 95% CI 0.22-0.9, P = 0.05). CONCLUSIONS: Adjuvant nadroparin did not improve RFS in patients with resected NSCLC. In this study, a high SUVmax predicted a greater likelihood of recurrence in the first year. CLINICAL TRIAL REGISTRATION: Netherlands Trial registry: NTR1250/1217.


Assuntos
Anticoagulantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Nadroparina/uso terapêutico , Pneumonectomia , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Pemetrexede/administração & dosagem , Tomografia por Emissão de Pósitrons
8.
J Thorac Oncol ; 14(8): 1360-1369, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31009812

RESUMO

INTRODUCTION: Inherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer. METHODS: We conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer. RESULTS: We detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722-0.820; p value 5.31 × 10-16), rs380286 (OR: 0.770, 95% CI: 0.723-0.820; p value 4.32 × 10-16), and rs4975616 (OR: 0.778, 95% CI: 0.730-0.829; p value 1.04 × 10-14). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate. CONCLUSIONS: We found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease.


Assuntos
Cromossomos Humanos Par 5 , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Telomerase/genética , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla/métodos , Técnicas de Genotipagem/métodos , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
10.
Carcinogenesis ; 40(3): 432-440, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-30590402

RESUMO

DNase I hypersensitive sites (DHS) are abundant in regulatory elements, such as promoter, enhancer and transcription factor binding sites. Many studies have revealed that disease-associated variants were concentrated in DHS-related regions. However, limited studies are available on the roles of DHS-related variants in lung cancer. In this study, we performed a large-scale case-control study with 20 871 lung cancer cases and 15 971 controls to evaluate the associations between regulatory genetic variants in DHS and lung cancer susceptibility. The expression quantitative trait loci (eQTL) analysis and pathway-enrichment analysis were performed to identify the possible target genes and pathways. In addition, we performed motif-based analysis to explore the lung-cancer-related motifs using sequence kernel association test. Two novel variants, rs186332 in 20q13.3 (C>T, odds ratio [OR] = 1.17, 95% confidence interval [95% CI]: 1.10-1.24, P = 8.45 × 10-7) and rs4839323 in 1p13.2 (T>C, OR = 0.92, 95% CI: 0.89-0.95, P = 1.02 × 10-6) showed significant association with lung cancer risk. The eQTL analysis suggested that these two SNPs might regulate the expression of MRGBP and SLC16A1, respectively. What's more, the expression of both MRGBP and SLC16A1 was aberrantly elevated in lung tumor tissues. The motif-based analysis identified 10 motifs related to the risk of lung cancer (P < 1.71 × 10-4). Our findings suggested that variants in DHS might modify lung cancer susceptibility through regulating the expression of surrounding genes. This study provided us a deeper insight into the roles of DHS-related genetic variants for lung cancer.


Assuntos
Desoxirribonuclease I/metabolismo , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
11.
Respiration ; 97(4): 337-347, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30554224

RESUMO

BACKGROUND: In lung cancer staging, mediastinal lymph nodes are currently aspirated using endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) based on size and FDG-PET avidity. EBUS strain elastography (SE) is a new technique that may help predict the presence of malignancy. However, a standardized assessment strategy for EBUS-SE measurement is lacking. OBJECTIVES: The aim of this study was to determine the optimal assessment strategy for investigating the predictive value of EBUS-SE in mediastinal lymph nodes. METHODS: Two qualitative visual analogue scale strain scores and two semiquantitative strain elastography measurements (a strain histogram and strain ratio) were acquired in 120 lymph nodes of 63 patients with (suspected) lung cancer. The dataset was randomized into an 80% training dataset to determine cut-off values. Performance was consecutively tested on the remaining 20% and the overall dataset. RESULTS: The semiquantitative mean histogram scoring strategy with a cut-off value of 78 (range 0-255) showed the best and most reproducible performance in prediction of malignancy with 93% overall sensitivity, 75% specificity, 69% positive predictive value, 95% negative predictive value, and 82% accuracy. Combining the EBUS-SE mean histogram scoring outcome with PET-CT information increased the post-test probability of disease in relevant clinical scenarios, having a positive test likelihood ratio of 4.16 (95% CI 2.98-8.13) and a negative test likelihood ratio of 0.14 (95% CI 0.04-2.81) in suspicious lymph nodes based on FDG-PET or CT imaging. CONCLUSIONS: EBUS-SE can potentially help predict lymph node malignancy in patients with lung cancer. The best semiquantitative assessment method is the mean strain histogram technique.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pulmonares/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Int J Epidemiol ; 48(3): 751-766, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30059977

RESUMO

BACKGROUND: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses. METHODS: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects. Next, we conducted an MR analysis of lung (16 396 cases, 13 013 controls) and head and neck cancer (4415 cases, 5013 controls) using eight genetic instruments for TL. Lastly, the 5p15.33 instrument and distinct 5p15.33 lung cancer risk loci were evaluated using two-sample mediation analysis, to quantify their direct and indirect, telomere-mediated, effects. RESULTS: The multi-allelic 5p15.33 instrument explained 1.49-2.00% of TL variation in our data (p = 2.6 × 10-9). The MR analysis estimated that a 1000 base-pair increase in TL increases risk of lung cancer [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.20-1.65] and lung adenocarcinoma (OR = 1.92, 95% CI: 1.51-2.22), but not squamous lung carcinoma (OR = 1.04, 95% CI: 0.83-1.29) or head and neck cancers (OR = 0.90, 95% CI: 0.70-1.05). Mediation analysis of the 5p15.33 instrument indicated an absence of direct effects on lung cancer risk (OR = 1.00, 95% CI: 0.95-1.04). Analysis of distinct 5p15.33 susceptibility variants estimated that TL mediates up to 40% of the observed associations with lung cancer risk. CONCLUSIONS: Our findings support a causal role for long telomeres in lung cancer aetiology, particularly for adenocarcinoma, and demonstrate that telomere maintenance partially mediates the lung cancer susceptibility conferred by 5p15.33 loci.


Assuntos
Adenocarcinoma de Pulmão/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Leucócitos/metabolismo , Neoplasias Pulmonares/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Homeostase do Telômero/genética , Telômero/metabolismo , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 5/genética , Feminino , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade
13.
Respir Physiol Neurobiol ; 259: 53-57, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30026086

RESUMO

BACKGROUND: Non-invasive ventilation (NIV) provides ventilatory support for patients with respiratory failure. However, the glottis can act as a closing valve, limiting effectiveness of NIV. This study investigates the patency of the glottis during NIV in patients with acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD). METHODS: Electrical activity of the diaphragm, flow, pressure and videolaryngoscopy were acquired. NIV was randomly applied in pressure support (PSV) and neurally adjusted ventilatory assist (NAVA) mode with two levels of support. The angle formed by the vocal cords represented glottis patency. RESULTS: Eight COPD patients with acute exacerbation requiring NIV were included. No differences were found in median glottis angle during inspiration or peak inspiratory effort between PSV and NAVA at low and high support levels. CONCLUSIONS: The present study showed that glottis patency during inspiration in patients with an acute exacerbation of COPD is not affected by mode (PSV or NAVA) or level of assist (5 or 15 cm H2O) during NIV.


Assuntos
Glote/patologia , Glote/fisiologia , Ventilação não Invasiva/métodos , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/terapia , Idoso , Diafragma/fisiopatologia , Feminino , Humanos , Laringoscopia , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Gravação de Videodisco
14.
Respiration ; 96(2): 206, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29953995
15.
BMJ Open Respir Res ; 5(1): e000295, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29862031

RESUMO

Introduction: Patients with lung cancer may present with additional lesions in the central airways. Earlier studies have shown a relationship between vessel diameter, pattern and grade of malignancy. High-definition (HD+) bronchoscopy with image enhancement techniques (i-scan) detected more vascular abnormalities but correlation with pathology has not yet been established. Methods: In this investigator-initiated, randomised, controlled, crossover, multicentre study in patients with suspected lung cancer, a HD+ bronchoscopy was performed with i-scan1 and i-scan2 settings in random order. Biopsies, visual grade and vascular pattern classification were obtained by endoscopists and blinded evaluation. Results: In 107 patients, vascular patterns were classified in 48 tumours. Abrupt-ending vessels were predominantly found in squamous cell carcinoma but overall correlation between vessel pattern and histology was not significant (p=0.339). Additional lesions were detected in 35 patients (33%) with a correlation between vessel pattern and high-grade (pre-)invasive lesions (p<0.001). In 8.4% of the patients, relevant second lesions were detected which determined treatment and staging in 3% of all patients. Interobserver agreement was excellent for visual grading of the airway epithelium, but low for classifying vascular patterns. No significant detection rate difference was found by blinded and unblinded evaluation. Conclusion: HD+ bronchoscopy with i-scan image enhancement readily detects additional lesions. In one-third of all the patients, additional lesions were detected. Their vascular pattern correlates to pathology outcome, but the interobserver correlation for vascular pattern classification is low. These lesions were relevant in 8.4% and affected treatment and work-up in 3% of the cases. Trial registration number: NCT02285426; Results.

16.
Ann Cardiothorac Surg ; 7(2): 227-236, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29707500

RESUMO

Background: In this study we focus on functional outcomes after (laryngo)tracheal resection and reconstruction for acquired benign (laryngo)tracheal stenosis, with a specific interest in the impact of laryngeal involvement on postoperative outcome. Methods: All patients who underwent (laryngo)tracheal surgery for benign pathology between 1996 and 2017 in our centre were included in this retrospective study. Surgical outcomes were procedural success rate, and airway- and voice-related complications. Functional results were assessed using (standardized) questionnaires for quality of life, sensation of dyspnea, swallowing function, and voice perception. Results: Of 119 consecutive patients, 47 underwent laryngotracheal resection and reconstruction and 72 underwent segmental tracheal surgery (78% with an end-to-end tracheal anastomosis and 22% with a cricotracheal anastomosis). Overall success rate was 92% and was similar for all groups, with an overall significant improvement in quality of life when compared to the preoperative situation. However, after laryngotracheal surgery, airway-related complications were more common when compared to segmental resections with an end-to-end tracheal anastomosis (30% versus 7%, P=0.003). Additionally, early voice alterations without recurrent nerve palsy were reported twice as often (34% versus 16%, P=0.034) and voice quality experienced during follow-up was significantly worse when compared to segmental resections. Overall response rate to the questionnaires on functional outcome was 63%. Conclusions: (Laryngo)tracheal surgery is safe and beneficial, with significant functional improvement during mid- and long-term follow-up. However, laryngeal involvement is a predictor for increased surgical airway-related complications. Additionally, voice alterations without recurrent nerve palsy are far more common after laryngotracheal resection and are a serious handicap. This aspect is underexposed in current literature and deserves further attention during preoperative counseling and patient follow-up. However, the results on functional outcome of this current study should be interpreted with caution due to the somewhat low response rate of the questionnaires.

18.
Int J Radiat Oncol Biol Phys ; 99(2): 434-441, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28871994

RESUMO

PURPOSE: To evaluate whether inclusion of incidental radiation dose to the cardiac atria and ventricles improves the prediction of grade ≥3 radiation pneumonitis (RP) in advanced-stage non-small cell lung cancer (AS-NSCLC) patients treated with intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS: Using a bootstrap modeling approach, clinical parameters and dose-volume histogram (DVH) parameters of lungs and heart (assessing atria and ventricles separately and combined) were evaluated for RP prediction in 188 AS-NSCLC patients. RESULTS: After a median follow-up of 18.4 months, 26 patients (13.8%) developed RP. Only the median mean lung dose (MLD) differed between groups (15.3 Gy vs 13.7 Gy for the RP and non-RP group, respectively; P=.004). The MLD showed the highest Spearman correlation coefficient (Rs) for RP (Rs = 0.21; P<.01). Most Rs of the lung DVH parameters exceeded those of the heart DVH parameters. After predictive modeling using a bootstrap procedure, the MLD was always included in the predictive model for grade ≥3 RP, whereas the heart DVH parameters were seldom included in the model. CONCLUSION: Incidental dose to the cardiac atria and ventricles did not improve RP risk prediction in our cohort of 188 AS-NSCLC patients treated with IMRT or VMAT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Órgãos em Risco/efeitos da radiação , Pneumonite por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Átrios do Coração/efeitos da radiação , Ventrículos do Coração/efeitos da radiação , Humanos , Pulmão/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Doses de Radiação , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Fatores de Tempo
19.
PLoS One ; 12(6): e0177875, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28594918

RESUMO

BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. CONCLUSIONS: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.


Assuntos
Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Análise da Randomização Mendeliana , Obesidade/complicações , Índice de Massa Corporal , Jejum , Humanos , Insulina/sangue , Resistência à Insulina , Funções Verossimilhança , Lipídeos/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/complicações , Obesidade/sangue , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores de Risco
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