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1.
BMC Bioinformatics ; 21(Suppl 14): 368, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998690

RESUMO

BACKGROUND: Lung cancer is the leading cause of the largest number of deaths worldwide and lung adenocarcinoma is the most common form of lung cancer. In order to understand the molecular basis of lung adenocarcinoma, integrative analysis have been performed by using genomics, transcriptomics, epigenomics, proteomics and clinical data. Besides, molecular prognostic signatures have been generated for lung adenocarcinoma by using gene expression levels in tumor samples. However, we need signatures including different types of molecular data, even cohort or patient-based biomarkers which are the candidates of molecular targeting. RESULTS: We built an R pipeline to carry out an integrated meta-analysis of the genomic alterations including single-nucleotide variations and the copy number variations, transcriptomics variations through RNA-seq and clinical data of patients with lung adenocarcinoma in The Cancer Genome Atlas project. We integrated significant genes including single-nucleotide variations or the copy number variations, differentially expressed genes and those in active subnetworks to construct a prognosis signature. Cox proportional hazards model with Lasso penalty and LOOCV was used to identify best gene signature among different gene categories. We determined a 12-gene signature (BCHE, CCNA1, CYP24A1, DEPTOR, MASP2, MGLL, MYO1A, PODXL2, RAPGEF3, SGK2, TNNI2, ZBTB16) for prognostic risk prediction based on overall survival time of the patients with lung adenocarcinoma. The patients in both training and test data were clustered into high-risk and low-risk groups by using risk scores of the patients calculated based on selected gene signature. The overall survival probability of these risk groups was highly significantly different for both training and test datasets. CONCLUSIONS: This 12-gene signature could predict the prognostic risk of the patients with lung adenocarcinoma in TCGA and they are potential predictors for the survival-based risk clustering of the patients with lung adenocarcinoma. These genes can be used to cluster patients based on molecular nature and the best candidates of drugs for the patient clusters can be proposed. These genes also have a high potential for targeted cancer therapy of patients with lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão/patologia , Genômica/métodos , Neoplasias Pulmonares/patologia , Transcriptoma , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Área Sob a Curva , Análise por Conglomerados , Variações do Número de Cópias de DNA , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Mapas de Interação de Proteínas/genética , Curva ROC , Fatores de Risco , Taxa de Sobrevida
2.
Medicine (Baltimore) ; 99(38): e21964, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957314

RESUMO

BACKGROUND: The aim of this study was to investigate the link between heart dose and overall survival, the link between heart dose and cardiac events and whether radiation-induced heart diseases were associated with overall survival in lung cancer radiotherapy. METHODS: We performed a literature search by using Pubmed, Embase, China National Knowledge Infrastructure (CNKI) databases. Pairs of reviewers independently screened literature according to the inclusion criteria, extracted data, assessed methodological quality, and publication bias. The primary end points included overall survival and cardiac events. I was calculated in a heterogeneity assessment. Publication bias was evaluated by using Begg funnel plot and Egger test. RESULTS: Ten studies including 1 randomized controlled trial, 3 post hoc analysis of prospective trials, and 6 cohort studies were identified. The meta-analysis showed that heart volume receiving ≥5 Gy (HV5) (hazard ratio [HR] = 1.01; 95% confidence interval [CI]: 1.00-1.01), heart volume receiving ≥30 Gy (HV30) (HR = 1.01; 95% CI: 1.00-1.02), heart volume receiving ≥50 Gy (HV50) (HR = 1.05; 95%CI: 1.00-1.10), and mean heart dose (MHD) (HR = 1.01; 95%CI:1.00-1.02) all were associated with worse overall survival. In addition, the MHD (HR = 1.03; 95% CI: 1.02-1.05), HV5 (HR = 1.02; 95% CI: 1.01-1.03), and HV30 (HR = 1.02; 95% CI: 1.01-1.03) were significantly associated with all grade cardiac events. Meanwhile, compared with those who did not receive radiotherapy, the radiotherapy group experienced a significantly increased risk for cardiac-specific mortality (HR = 1.297; 95% CI: 1.213-1.387). However, the results did not show that cardiac events were associated with overall survival in lung cancer radiotherapy (HR = 1.472; 95% CI: 0.988-2.193). CONCLUSION: Exposure of the heart to radiation increased the risk of cardiac events during radiotherapy for lung cancer. Meanwhile, heart dose including HV5 and HV30 were predictors of overall survival in lung cancer radiotherapy. It is necessary to constrain the heart dose when perform thoracic radiation therapy to decrease the incidence of cardiac events and improve the overall survival.


Assuntos
Volume Cardíaco/efeitos da radiação , Cardiopatias/etiologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/epidemiologia , Cardiopatias/mortalidade , Estudos Prospectivos , Doses de Radiação , Lesões por Radiação/mortalidade
3.
BMC Pulm Med ; 20(1): 235, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873264

RESUMO

BACKGROUND: Osteopontin (OPN) is closely related to tumor occurrence and metastasis. This study explored the clinical value of serum OPN levels in small cell lung cancer (SCLC) patients. METHODS: The ELISA method was used to determine the OPN level of 96 SCLC patients before and after first-line chemotherapy, and compared with 60 healthy controls. RESULTS: The serum OPN level of SCLC patients before treatment was significantly higher than that of the healthy control (P < 0.001). Serum OPN levels were related to disease stage, tumor size, and lymph node metastasis (P = 0.012, 0.034, and 0.037, respectively). Serum OPN level decreased after first-line chemotherapy (P = 0.019), which was related to treatment response (P = 0.011). The serum OPN level was an independent predictor of overall survival. CONCLUSIONS: The serum OPN level can be used as a biomarker to predict treatment response and survival of SCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Osteopontina/sangue , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
4.
BMC Pulm Med ; 20(1): 240, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912174

RESUMO

BACKGROUND: As part of the multinational I-O Optimise research initiative, this retrospective cohort study of patients with advanced non-small cell lung cancer (NSCLC) evaluated real-world treatment patterns and survival prior to immunotherapy reimbursement in Portugal. METHODS: This study utilized a database held by IPO-Porto, Portugal's largest oncology hospital. Adult patients diagnosed with stage IIIB or IV NSCLC from January 2012 to December 2016 at IPO-Porto, with follow-up to June 2017, were included. Treatment analyses were performed from 2015 onwards. Kaplan-Meier methods were used for overall survival (OS). Factors associated with OS and systemic anti-cancer therapy (SACT) treatment were assessed using multivariate statistical models. RESULTS: Of 1524 patients diagnosed with NSCLC at IPO-Porto, 1008 patients had advanced disease (stage IIIB: 10.1%, 154/1524, stage IV: 56.0%, 854/1524). For those with advanced disease, median age was 65 years (range: 21-92) and 75.6% (762/1008) were male. Median OS (interquartile range [IQR]) was 11.4 (5.2-26.9) months for stage IIIB and 6.3 (2.4-15.0) months for stage IV. Factors associated with decreased risk of death included female sex and epidermal growth factor receptor gene (EGFR)/anaplastic lymphoma kinase gene (ALK) mutations/rearrangements; factors associated with increased risk of death included older age and stage IV disease. Among patients diagnosed in 2015 or 2016, 75.8% (297/392) received ≥1 line of SACT. Platinum-based chemotherapy was the most common first-line therapy (non-squamous cell carcinoma [NSQ]: 72.9%; squamous cell carcinoma [SQ] 87.3%, 55/63; patients with EGFR/ALK mutations/rearrangements primarily received tyrosine kinase inhibitors). The likelihood of receiving SACT was lower in older patients and those diagnosed with stage IV disease. Patients not receiving SACT had poor survival outcomes (median OS [IQR]: NSQ, 1.8 [1.1-3.1] months; SQ, 2.3 (1.3-3.4) months), while median OS (IQR) in SACT-treated patients was 12.6 (6.1-24.5) months for NSQ and 10.3 (5.7-15.9) months for SQ. CONCLUSIONS: This real-world data analysis from a large Portuguese oncology hospital demonstrates a high disease burden for advanced NSCLC in the pre-immunotherapy era, with nearly one-quarter of patients not receiving SACT. Even in patients receiving SACT, median survival was only about 1 year.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Feminino , Humanos , Imunoterapia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Portugal/epidemiologia , Padrões de Prática Médica , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
5.
Medicine (Baltimore) ; 99(33): e21798, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872080

RESUMO

This study is to establish the nomogram model and provide clinical therapy decision-making for extensive-stage small-cell lung cancer (ES-SCLC) patients with different metastatic sites using the Surveillance, Epidemiology, and End Results (SEER) Program.A total of 10,025 patients of ES-SCLC with metastasis from January 2010 to December 2016 were enrolled from the SEER database. All samples were randomly divided into a derivation cohort and a validation cohort, and the derivation cohort was divided into 6 groups by different metastatic sites: bone, liver, lung, brain, multiple organs, and other organs. Using Cox proportional hazards models to analyze candidate prognostic factors, screening out the independent prognostic factors to establish the nomogram. Compare the different models by Net reclassification improvement and integrated discrimination improvement. Concordance index (C-index) and the calibration curve were used to verify the prediction efficiency of the nomogram in the derivation cohort and validation cohort.In the derivation cohort, the median overall survival was 7 months. The overall survival rates at 6-month, 1-year, and 2-year were 55.07%, 24.61%, and 7.56%, respectively. The median survival time was 10, 8, 7, 9, 7, and 6 months for the 6 groups of different metastatic sites: other, bone, liver, lung, brain, and multiple organs, respectively. Age, sex, race, T, N, distant metastatic site, and chemotherapy were contained in the final nomogram prognostic model. The C-index was 0.6569777 in the derivation cohort and 0.8386301 in the validation cohort.The survival time of ES-SCLC patients with different metastatic sites was significantly different. The nomogram can effectively predict the prognosis of individuals and provide a basis for clinical decision-making.


Assuntos
Neoplasias Pulmonares/mortalidade , Nomogramas , Carcinoma de Pequenas Células do Pulmão/mortalidade , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Programa de SEER , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Estados Unidos/epidemiologia
7.
N Engl J Med ; 383(14): 1328-1339, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32997907

RESUMO

BACKGROUND: The efficacy and safety of the anti-programmed death ligand 1 (PD-L1) monoclonal antibody atezolizumab, as compared with those of platinum-based chemotherapy, as first-line treatment for patients with metastatic non-small-cell lung cancer (NSCLC) with PD-L1 expression are not known. METHODS: We conducted a randomized, open-label, phase 3 trial involving patients with metastatic nonsquamous or squamous NSCLC who had not previously received chemotherapy and who had PD-L1 expression on at least 1% of tumor cells or at least 1% of tumor-infiltrating immune cells as assessed by the SP142 immunohistochemical assay. Patients were assigned in a 1:1 ratio to receive atezolizumab or chemotherapy. Overall survival (primary end point) was tested hierarchically according to PD-L1 expression status among patients in the intention-to-treat population whose tumors were wild-type with respect to EGFR mutations or ALK translocations. Within the population with EGFR and ALK wild-type tumors, overall survival and progression-free survival were also prospectively assessed in subgroups defined according to findings on two PD-L1 assays as well as by blood-based tumor mutational burden. RESULTS: Overall, 572 patients were enrolled. In the subgroup of patients with EGFR and ALK wild-type tumors who had the highest expression of PD-L1 (205 patients), the median overall survival was longer by 7.1 months in the atezolizumab group than in the chemotherapy group (20.2 months vs. 13.1 months; hazard ratio for death, 0.59; P = 0.01). Among all the patients who could be evaluated for safety, adverse events occurred in 90.2% of the patients in the atezolizumab group and in 94.7% of those in the chemotherapy group; grade 3 or 4 adverse events occurred in 30.1% and 52.5% of the patients in the respective groups. Overall and progression-free survival favored atezolizumab in the subgroups with a high blood-based tumor mutational burden. CONCLUSIONS: Atezolizumab treatment resulted in significantly longer overall survival than platinum-based chemotherapy among patients with NSCLC with high PD-L1 expression, regardless of histologic type. (Funded by F. Hoffmann-La Roche/Genentech; IMpower110 ClinicalTrials.gov number, NCT02409342.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sobrevida
8.
Medicine (Baltimore) ; 99(31): e20076, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756072

RESUMO

C-terminal binding protein-2 (CtBP2) a transcriptional corepressor, has been reported to involve in tumorigenesis and progression and predict a poor prognosis in several human cancers. However, few studies on CtBP2 in lung cancer tissues have been performed. In the present study, we first explored the CtBP2 gene expression profile from the the cancer genome atlas (TCGA) datasets, then western blot analysis and immunohistochemistry were performed to investigate and verified whether lung adenocarcinoma (LUAD) tissues exhibit deregulated CtBP2 expression. We evaluated the correlations between CtBP2 expression and the clinicopathological characteristics, and Kaplan-Meier survival analyses were performed to estimate the effect of CtBP2 expression on prognosis of LUAD patients. The results revealed that CtBP2 expression was significantly upregulated in LUAD tissues compared with normal lung tissues. Furthermore, increasing CtBP2 expression in LUAD was significantly associated with tumor differentiation (P = .028), tumor node metastasis (TNM) stage (P = .042). CtBP2 expression was significantly correlated with LUAD patients' survival (P = .028). In conclusion, the present study revealed that CtBP2 protein is a novel prognostic marker for LUAD. A further large-scale study is needed to confirm the present results.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Oxirredutases do Álcool/análise , Proteínas Correpressoras/análise , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma de Pulmão/química , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/análise , Western Blotting , Feminino , Humanos , Pulmão/química , Neoplasias Pulmonares/química , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sobrevida
9.
Medicine (Baltimore) ; 99(31): e20878, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756080

RESUMO

This case series aimed to preliminarily evaluate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) in patients with lung, renal, gastric, and other non-liver cancers.Twenty-four patients who underwent DEB-TACE or DEB-TACE combined with other therapies were reviewed in this case series. Treatment responses were assessed at 1 month after treatment according to the modified Response Evaluation Criteria in Solid Tumors. Overall survival (OS) and adverse events were recorded.In the total patients, the objective response and disease control rate were 79.2% and 87.5%, respectively. And the mean OS in total patients was 14.7 months (95% confidence interval: 9.6-19.9 months). The number of patients who had generalized aches, nausea, vomit, fever, abdominal discomfort, chest discomfort, elevated blood pressure, cough, loss of appetite, and headache in total patients were 7 (29.2%), 11 (45.8%), 6 (25.0%), 2 (8.3%), 3 (12.5%), 3 (12.5%), 1 (4.2%), 1 (4.2%), 1 (4.2%), and 1 (4.2%), respectively. The objective response rates in patients with lung, renal, gastric, and other non-liver cancer were 70.0%, 85.7%, 100.0%, and 80.0%, respectively. In patients with lung, renal, gastric, and other non-liver cancers, the mean values of the OSs were 13.4 months, 12.4 months, 7.6 months, and 20.3 months, respectively. And the most common adverse events in lung cancer patients, renal carcinoma patients, gastric cancer patients, and patients with other non-liver cancers were post-embolization syndrome.DEB-TACE may be an effective and safe therapeutic option in patients with lung, renal, gastric, and other non-liver cancers.


Assuntos
Quimioembolização Terapêutica/métodos , Neoplasias/terapia , Idoso , Quimioembolização Terapêutica/efeitos adversos , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Microesferas , Pessoa de Meia-Idade , Neoplasias/mortalidade , Critérios de Avaliação de Resposta em Tumores Sólidos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Análise de Sobrevida
10.
Medicine (Baltimore) ; 99(31): e21339, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756121

RESUMO

Patients with non-small-cell lung cancer (NSCLC) often have a poor prognosis when brain metastases (BM) occur. This study aimed to evaluate the prognostic factors of BM in newly diagnosed NSCLC patients and construct a nomogram to predict the overall survival (OS).We included NSCLC patients with BM newly diagnosed from 2010 to 2015 in Surveillance, Epidemiology, and End Results database. The independent prognostic factors for NSCLC with BM were determined by Cox proportional hazards regression analysis. We then constructed and validated a nomogram to predict the OS of NSCLC with BM.We finally included 4129 NSCLC patients with BM for analysis. Age, race, sex, liver metastasis, primary site, histologic type, grade, bone metastasis, T stage, N stage, surgery, chemotherapy, and lung metastasis were identified as the prognostic factors for NSCLC with BM and integrated to establish the nomogram. The calibration, receiver operating characteristic curve, and decision curve analyses also showed that the clinical prediction model performed satisfactorily in predicting prognosis.A clinical prediction model was constructed and validated to predict individual OS for NSCLC with BM. The establishment of this clinical prediction model has great significance for clinicians and individuals.


Assuntos
Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Nomogramas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Curva ROC , Adulto Jovem
11.
Medicine (Baltimore) ; 99(31): e21490, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756179

RESUMO

BACKGROUND: Whether the combination of gefitinib and chemotherapy is beneficial for advanced non-small cell lung cancer (NSCLC) remains controversial. This study aimed to summarize the currently available evidence and compare the efficacy and safety of gefitinib combined with chemotherapy versus chemotherapy alone for treating advanced NSCLC. METHODS: Literature on comparing the effects of gefitinib combined with chemotherapy and chemotherapy alone in treating NSCLC was retrieved from the PubMed, EMBASE and Cochrane Database. The primary outcome measures included progression-free survival (PFS) and overall survival (OS). Revman 5.3 was used for data processing. RESULTS: Seven randomized controlled trials were included, involving a total of 1418 patients. There appeared a significant improvement in PFS (hazard ratio (HR) = 0.60 [95% CI 0.43, 0.82], P = .001) after treatment with gefitinib combined with chemotherapy when compared with chemotherapy alone. The subgroup analysis showed a significant advantage of sequential administration (HR = 0.67 [95% CI 0.57, 0.79], P < .00001). There was no significant improvement in OS (HR = 0.92 [95% CI 0.71, 1.20], P = .54), and no significant improvement in overall response rate (ORR) (HR = 0.98 [95% CI 0.67, 1.44], P = .93). The risks of rash and diarrhea (odds ratios) were higher in gefitinib combined with chemotherapy group when compared with chemotherapy alone, and there were significant differences on grade 3/4 rash and thrombocytopenia between 2 groups. CONCLUSION: Gefitinib combined with chemotherapy is superior to chemotherapy alone in PFS, sequential administration prolongs the patients' PFS, however, a survival advantage is not shown in OS or ORR. Gefitinib combined with chemotherapy aggravates rash, diarrhea and thrombocytopenia.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Gefitinibe/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Exantema/induzido quimicamente , Feminino , Gefitinibe/efeitos adversos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Trombocitopenia/induzido quimicamente , Resultado do Tratamento
12.
Medicine (Baltimore) ; 99(30): e21368, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791745

RESUMO

Pulmonary metastasectomy is considered to be a feasible method for selected colorectal cancer (CRC) patients. This study aimed to optimize the individualized surgical strategy of pulmonary metastasectomy, especially in choice of surgery extent and systematic mediastinal lymph nodes dissection.Data of 267 CRC patients who underwent pulmonary metastasectomy from July 2011 to July 2017 in Shanghai Cancer Center Fudan University were reviewed. Recurrence-free survival (RFS), overall survival (OS) and other clinical characteristics were compared between patients who accepted different surgical strategy.A total of 93 (34.8%) patients underwent lobectomy, 162 (60.7%) wedge resection, and 12 (4.5%) segmentectomy. Mediastinal lymph nodes dissection or sampling was performed in 106 (39.7%) patients. The median follow-up phase was 32.5 months (range 7.2-104.7 months). Patients were divided into 2 groups according to the surgical extent, lobectomy group and sublobar resection group. The median RFS and OS were 46.4 and 76.5 months for patients underwent, respectively. In the patients whose tumor diameter was ≥ 1.5 cm, RFS (5-year; 44.9% vs 29.8%, log-rank P = .03; hazard ratio, 0.71; 95% CI 0.52-0.89, P = .026) was better in the lobectomy group; however, no difference was found in OS. Meanwhile, in the patients whose tumor size was <1.5 cm, no difference was observed in RFS, as well as in OS. In the patients with metastatic lesion size ≥1.5 cm, a trend towards better RFS was found in patients received lymph nodes dissection, but it did not reach statistical significance.Lobectomy has more curative significance for CRC patients with single pulmonary metastatic lesion ≥1.5 cm. Systematic mediastinal lymph nodes dissection did not improve clinical outcome for CRC patients occurred pulmonary metastasis.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Pulmonares/cirurgia , Pulmão/cirurgia , Pneumonectomia/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Cancer Treat Rev ; 89: 102085, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32771858

RESUMO

Immune checkpoint inhibitors (ICIs) represent one of the main steps forward for the treatment of advanced or metastatic non-small-cell lung cancer (NSCLC), without oncogenic driver alterations. Despite this recent progress, only a minority of patients achieve a broad and durable benefit and another proportion report poor survival and sometimes fast disease progression, confirming the need to optimise the patient's selection. To date, several issues are unsolved about how to personalise the immunotherapy treatment for individual patients. In this review, analysing data from pivotal randomised clinical trials (RCTs), we discuss patient baseline clinical and demographic features, including sex, age, ECOG performance status, smoking habit and specific site of metastases (liver, bone and brain) that may influence the efficacy outcomes in patients treated with ICIs. The high performance of the ICIs blurred the vision on different efficacy-limiting factors, which require extensive evaluation to improve the understanding ofthe tumour-specificimmune response, in which clinical drivers could be useful for better patient stratification.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Medicine (Baltimore) ; 99(34): e21715, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846789

RESUMO

BACKGROUND: Stereotactic body radiotherapy (SBRT) superseded conventional radiotherapy (CRT) for the treatment of patients with inoperable early stage non-small cell lung cancer (NSCLC) over a decade ago. However, the direct comparisons of the outcomes of SBRT and CRT remain controversial. This meta-analysis was performed to compare the survival and safety of SBRT and CRT in patients with inoperable stage I NSCLC. METHODS: We systematically searched the Cochrane Library, Embase, PubMed, Web of Science, Ovid MEDLINE, ScienceDirect, Scopus and Google Scholar for relevant articles. Overall survival (OS), progression-free survival (PFS), lung cancer-specific survival (LCSS), local control rate (LCR) and adverse effects (AEs) were the primary outcomes. RESULTS: We identified 11,110 articles, 17 of which were eventually included in this study; these 17 articles had 17,973 patients (SBRT: 7395; CRT: 10,578). Compared to CRT for the treatment of inoperable stage I NSCLC, SBRT had superior survival in terms of OS (hazard ratio [HR]: 0.66, 95% confidence interval [CI]: 0.62-0.70, P < .00001), LCSS (HR: 0.42 [0.35-0.50], P < .00001), and PFS (HR: 0.34 [0.25-0.48], P < .00001). The 4-year OS rate (OSR); 4-year LCSS rate (LCSSR); 3-year local control rate (LCR); 5-year PFS rate (PFSR) with SBRT were all higher than those with CRT. With regard to all-grade AEs, the SBRT group had a significantly lower rate of dyspnea, esophagitis and radiation pneumonitis; no significant difference was found in grade 3-5 AEs (risk ratio [RR]: 0.68 [0.30-1.53], P = .35). CONCLUSIONS: With better survival and a lower rate of dyspnea, esophagitis and radiation pneumonitis than CRT, SBRT appears to be more suitable for patients with inoperable stage I NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Fatores Etários , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Lesões por Radiação/epidemiologia , Radiocirurgia/efeitos adversos , Taxa de Sobrevida
15.
Medicine (Baltimore) ; 99(32): e21478, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769881

RESUMO

The aim of current study was to use Weighted Gene Coexpression Network Analysis (WGCNA) to identify hub genes related to the incidence and prognosis of KRAS mutant (MT) lung adenocarcinoma (LUAD).We involved 184 stage IIB to IV LUAD samples and 59 normal lung tissue samples from The Cancer Genome Atlas (TCGA) database. The R package "limma" was used to identify differentially expressed genes (DEGs). WGCNA and survival analyses were performed by R packages "WGCNA" and "survival," respectively. The functional analyses were performed by R package "clusterProfiler" and GSEA software. Network construction and MCODE analysis were performed by Cytoscape_v3.6.1.Totally 2590 KRAS MT specific DEGs were found between LUAD and normal lung tissues, and 10 WGCNA modules were identified. Functional analysis of the key module showed the ribosome biogenesis related terms were enriched. We observed the expression of 8 genes were positively correlated to the worse survival of KRAS MT LUAD patients, the 7 of them were validated by Kaplan-Meier plotter database (kmplot.com/) (thymosin Beta 10 [TMSB10], ribosomal Protein S16 [RPS16], mitochondrial ribosomal protein L27 [MRPL27], cytochrome c oxidase subunit 6A1 [COX6A1], HCLS1-associated protein X-1 [HAX1], ribosomal protein L38 [RPL38], and ATP Synthase Membrane Subunit DAPIT [ATP5MD]). The GSEA analysis found mTOR and STK33 pathways were upregulated in KRAS MT LUAD (P < .05, false discovery rate [FDR] < 0.25).In summary, our study firstly used WGCNA to identify hub genes in the development of KRAS MT LUAD. The identified prognostic factors would be potential biomarkers in clinical use. Further molecular studies are required to confirm the mechanism of those genes in KRAS MT LUAD.


Assuntos
Adenocarcinoma de Pulmão/genética , Redes Reguladoras de Genes/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma de Pulmão/mortalidade , Biomarcadores Tumorais/genética , Biologia Computacional , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Mutação , Prognóstico , RNA Mensageiro/metabolismo , Análise de Sobrevida
16.
N Engl J Med ; 383(7): 640-649, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32786189

RESUMO

BACKGROUND: Lung cancer is made up of distinct subtypes, including non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Although overall mortality from lung cancer has been declining in the United States, little is known about mortality trends according to cancer subtype at the population level because death certificates do not record subtype information. METHODS: Using data from Surveillance, Epidemiology, and End Results (SEER) areas, we assessed lung-cancer mortality and linked deaths from lung cancer to incident cases in SEER cancer registries. This allowed us to evaluate population-level mortality trends attributed to specific subtypes (incidence-based mortality). We also evaluated lung-cancer incidence and survival according to cancer subtype, sex, and calendar year. Joinpoint software was used to assess changes in incidence and trends in incidence-based mortality. RESULTS: Mortality from NSCLC decreased even faster than the incidence of this subtype, and this decrease was associated with a substantial improvement in survival over time that corresponded to the timing of approval of targeted therapy. Among men, incidence-based mortality from NSCLC decreased 6.3% annually from 2013 through 2016, whereas the incidence decreased 3.1% annually from 2008 through 2016. Corresponding lung cancer-specific survival improved from 26% among men with NSCLC that was diagnosed in 2001 to 35% among those in whom it was diagnosed in 2014. This improvement in survival was found across all races and ethnic groups. Similar patterns were found among women with NSCLC. In contrast, mortality from SCLC declined almost entirely as a result of declining incidence, with no improvement in survival. This result correlates with limited treatment advances for SCLC in the time frame we examined. CONCLUSIONS: Population-level mortality from NSCLC in the United States fell sharply from 2013 to 2016, and survival after diagnosis improved substantially. Our analysis suggests that a reduction in incidence along with treatment advances - particularly approvals for and use of targeted therapies - is likely to explain the reduction in mortality observed during this period.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Feminino , Humanos , Incidência , Neoplasias Pulmonares/epidemiologia , Masculino , Mortalidade/tendências , Programa de SEER , Fatores Sexuais , Estados Unidos/epidemiologia
17.
Medicine (Baltimore) ; 99(34): e21369, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846757

RESUMO

Although treatments have improved significantly in recent years, the prognosis of patients with non-small cell lung cancer (NSCLC) remains poor. miR-335 has been demonstrated to play the antitumor role in several cancer types. Its expression was reduced in NSCLC tissues relative to noncancerous adjacent tissues. Furthermore, downregulation of miR-335 in A459 lung cancer cells promoted cell proliferation. In the present study, we aimed to investigate the clinical significance and prognostic value of miR-335 in NSCLC.The lung cancer tissues and adjacent nontumor lung tissues were obtained from 131 patients who underwent the primary surgical resection at Lianyungang First People's Hospital. Student t test was used to distinguish differences between groups. χ test was involved for analysis of clinicopathological data. The overall survival was analyzed by the Kaplan-Meier method and the log rank test. Multiple Cox proportional hazards regression analysis was carried out to identify the independent factors that had a significant impact on patient survival.miR-335 was significantly lower in NSCLC samples compared to non-cancerous samples (P < .001). The expression level of miR-335 was significantly correlated with tumor histology (P = .028), lymph node metastasis (P = .002), differentiation degree (P < .001), and pathological TNM stage (P < .001). The log-rank test indicated that patients with decreased miR-335 expression experienced poor overall survival in NSCLC (P = .029).The results of the present study indicated that miR-335 was down-expressed in NSCLC, and is associated with tumor progression and poor prognosis, suggesting that the expression of miR-335 might be an independent prognostic factor of overall survival in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , China/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico
18.
J Cancer Res Clin Oncol ; 146(11): 2851-2859, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32743759

RESUMO

PURPOSE: TP53/EGFR co-mutation has been reported to affect the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma (LUAD). However, its impact on survival is unclear. In this analysis, we explored the prognostic effect of TP53/EGFR co-mutation in LUAD. METHODS: Clinical data and transcriptome sequencing of LUAD patients with matched genomic data were downloaded from the Cancer Genome Atlas (TCGA) database for overall survival (OS) analysis. Differential expression genes (DEGs) were recognized by R software and bioconductor package. Clusterprofiler was used for functional analysis. STRING was used for estimating PPI information and plug-in CytoHubba to screen hub modules in Cytoscape. The association between tumor mutation burden (TMB) and survival was also analyzed. RESULTS: OS was shorter for patients carrying TP53 mutation (MUT) than that of wild type (WT) (37.7 m vs 52.8 m; p = 0.040, HR = 1.38, 95% CI 1.01-1.89). Dual TP53/EGFR-MUT was associated with inferior OS compared with the dual WT/WT cohort (38.4 m vs 51.9 m; p = 0.023, HR 1.83, 95% CI 0.95-3.52). 316 DEGs between dual TP53/EGFR-MUT and dual WT/WT samples were obtained and functional analysis made known that DEGs were strikingly enriched in regulating the metabolism of important amino acids, cell division, cell cycle regulation, cell adhesion, and extracellular matrix composition. KEGG analysis discovered that DEGs were mainly enriched in signaling pathways such as PI3K-Akt, cytokine-cytokine receptor interaction, focal adhesions, and extracellular matrix receptor interaction. PPI network suggested that GPC3, CCL28, GPR37, and NPY genes were up-regulated in dual mutation samples. OS in the high TMB cohort was significantly better than that in the low TMB in patients with TP53 MUT(43.2 m vs 32.4 m; P = 0.007, HR = 0.52, 95% CI: 0.34-0.81), as well as in the combination of TP53 MUT and EGFR WT group (44.4 m vs 31.2 m; P = 0.021, HR = 0.55, 95% CI 0.34 - 0.89). CONCLUSIONS: TP53 MUT is a poor prognostic factor in LUAD patients, and the prognosis of TP53/EGFR co-mutation is worse. GPC3, CCL28, GPR37, and NPY may be novel prognostic markers and potential therapeutic targets for patients with dual TP53/EGFR mutation LUAD.


Assuntos
Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Proteína Supressora de Tumor p53/genética , Adenocarcinoma de Pulmão/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/genética , Feminino , Genes erbB-1 , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
19.
PLoS One ; 15(8): e0236021, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745082

RESUMO

BACKGROUND: The National Lung Screening Trial (NLST) demonstrated that annual screening with low dose CT in high-risk population was associated with reduction in lung cancer mortality. Nonetheless, the leading cause of mortality in the study was from cardiovascular diseases. PURPOSE: To determine whether the used machine learning automatic algorithms assessing coronary calcium score (CCS), level of liver steatosis and emphysema percentage in the lungs are good predictors of cardiovascular disease (CVD) mortality and incidence when applied on low dose CT scans. MATERIALS AND METHODS: Three fully automated machine learning algorithms were used to assess CCS, level of liver steatosis and emphysema percentage in the lung. The algorithms were used on low-dose computed tomography scans acquired from 12,332 participants in NLST. RESULTS: In a multivariate analysis, association between the three algorithm scores and CVD mortality have shown an OR of 1.72 (p = 0.003), 2.62 (p < 0.0001) for CCS scores of 101-400 and above 400 respectively, and an OR of 1.12 (p = 0.044) for level of liver steatosis. Similar results were shown for the incidence of CVD, OR of 1.96 (p < 0.0001), 4.94 (p < 0.0001) for CCS scores of 101-400 and above 400 respectively. Also, emphysema percentage demonstrated an OR of 0.89 (p < 0.0001). Similar results are shown for univariate analyses of the algorithms. CONCLUSION: The three automated machine learning algorithms could help physicians to assess the incidence and risk of CVD mortality in this specific population. Application of these algorithms to existing LDCT scans can provide valuable health care information and assist in future research.


Assuntos
Doenças Cardiovasculares/mortalidade , Aprendizado de Máquina , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Fumar Cigarros/efeitos adversos , Fumar Cigarros/epidemiologia , Ensaios Clínicos Fase III como Assunto , Vasos Coronários/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Enfisema/diagnóstico , Enfisema/epidemiologia , Enfisema/etiologia , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/epidemiologia , Feminino , Humanos , Fígado/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/mortalidade , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , National Cancer Institute (U.S.) , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Estados Unidos/epidemiologia
20.
Eur J Cardiothorac Surg ; 58(3): 598-604, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32856063

RESUMO

OBJECTIVES: There is currently a lack of clinical data on the novel beta-coronavirus infection [caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] and concomitant primary lung cancer. Our goal was to report our experiences with 5 patients treated for lung cancer while infected with SARS-CoV-2. METHODS: We retrospectively evaluated 5 adult patients infected with SARS-CoV-2 who were admitted to our thoracic surgery unit between 29 January 2020 and 4 March 2020 for surgical treatment of a primary lung cancer. Clinical data and outcomes are reported. RESULTS: All patients were men with a mean age of 74.0 years (range 67-80). Four of the 5 patients (80%) reported chronic comorbidities. Surgery comprised minimally invasive lobectomy (2 patients) and segmentectomy (1 patient), lobectomy with en bloc chest wall resection (1 patient) and pneumonectomy (1 patient). Mean chest drain duration was 12.4 days (range 8-22); mean hospital stay was 33.8 days (range 21-60). SARS-CoV-2-related symptoms were fever (3 patients), persistent cough (3 patients), diarrhoea (2 patients) and syncope (2 patients); 1 patient reported no symptoms. Morbidity related to surgery was 60%; 30-day mortality was 40%. Two patients (1 with a right pneumonectomy, 74 years old; 1 with a lobectomy with chest wall resection and reconstruction, 70 years old), developed SARS-CoV-2-related lung failure leading to death 60 and 32 days after surgery, respectively. CONCLUSIONS: Lung cancer surgery may represent a high-risk factor for developing a severe case of coronavirus disease 2019, particularly in patients with advanced stages of lung cancer. Additional strategies are needed to reduce the risk of morbidity and mortality from SARS-CoV-2 infection during treatment for lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Infecções por Coronavirus/diagnóstico , Infecção Hospitalar/prevenção & controle , Neoplasias Pulmonares/cirurgia , Pneumonia Viral/diagnóstico , Síndrome Respiratória Aguda Grave/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Técnicas de Laboratório Clínico , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Seguimentos , Mortalidade Hospitalar , Humanos , Itália , Tempo de Internação , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pandemias , Pneumonectomia/métodos , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Estudos Retrospectivos , Amostragem , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/mortalidade , Cirurgia Torácica Vídeoassistida/métodos , Resultado do Tratamento
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