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1.
Medicine (Baltimore) ; 99(45): e23172, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33158004

RESUMO

This study aimed to investigate the prognostic value of PD-L1 in Chinese patients with non-small cell lung carcinoma (NSCLC).In this retrospective study, 97 patients with NSCLC were consecutively recruited. The expression profiling of PD-1, PD-L1, p53 and Ki-67 was detected by immunohistochemistry. Median survival time was estimated by Kaplan-Meier survival curve with log-rank test. Risk factors were evaluated by Cox Proportional Hazards regression models.The median tumor size was larger (3.5 cm) among patients with positive PD-L1 expression, compared to those with negative expression (2.0 cm; P < .01). Compared to those with negative PD-L1 expression, patients with positive PD-L1 expression had significantly higher rates of nerve invasion (26.3% vs 5.0%; P < .01), blood vessel invasion (47.4% vs 20.0%; P < .01) and lymph node metastasis (64.9% vs 27.5%; P < .01), more advanced tumor stage (P < .01) and Ki-67 index (P < .01). PD-L1 expression status was not significantly associated with disease-free (DFS) or overall survival (OS). However, for patients with advanced disease, PD-L1 positive expression was related to worse outcome (HR: 4.13; 95% CI: 1.06-16.12).Positive PD-L1 expression is associated with more aggressive pathological features and poorer prognosis in advanced stage NSCLC.


Assuntos
Antígeno B7-H1/biossíntese , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Idoso , Antígeno B7-H1/análise , Carcinoma Pulmonar de Células não Pequenas/química , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/química , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
2.
Medicine (Baltimore) ; 99(42): e22603, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080694

RESUMO

The derived neutrophil-lymphocyte ration (dNLR) is a systemic inflammatory marker.The present study focusing on the prognostic value of pre-treatment dNLR in patients of early stage non-small cell lung cancer (NSCLC).From 2012 to 2016, patients with newly diagnosed early stage NSCLC were investigated. Only these who treated with stereotactic ablative radiotherapy (SABR) were enrolled in this study. dNLR was calculated from complete blood count prior to SABR. The optimal cut-off value of dNLR was determined by receiver operating curve. Kaplan-Meier curves and Cox proportional models were used to analyze the impact of pre-treatment dNLR on disease free survival (DFS) and overall survival (OS).There were 69 patients eligible for analysis, the median follow-up period was 30.9 months. Calculated by receiver operating characteristic curves, the optimal cut off value of dNLR was 1.99. Kaplan-Meier curves demonstrated that a decreased dNLR was correlated with favorable DFS and OS. In univariate analysis, high dNLR was associated with decreased survival; moreover, multivariate analysis revealed that a decreased dNLR was an independent significant favorable prognostic factor for both DFS and OS.An elevated pre-treatment dNLR may be an independent prognostic biomarker for DFS and OS in patients with early stage NSCLC that are eligible for SABR. dNLR is a reliable, inexpensive, simple, and readily available tool for risk-stratification and should be considered in daily clinical practice.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , China/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Nat Commun ; 11(1): 5228, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067442

RESUMO

Two major treatment strategies employed in non-small cell lung cancer, NSCLC, are tyrosine kinase inhibitors, TKIs, and immune checkpoint inhibitors, ICIs. The choice of strategy is based on heterogeneous biomarkers that can dynamically change during therapy. Thus, there is a compelling need to identify comprehensive biomarkers that can be used longitudinally to help guide therapy choice. Herein, we report a 18F-FDG-PET/CT-based deep learning model, which demonstrates high accuracy in EGFR mutation status prediction across patient cohorts from different institutions. A deep learning score (EGFR-DLS) was significantly and positively associated with longer progression free survival (PFS) in patients treated with EGFR-TKIs, while EGFR-DLS is significantly and negatively associated with higher durable clinical benefit, reduced hyperprogression, and longer PFS among patients treated with ICIs. Thus, the EGFR-DLS provides a non-invasive method for precise quantification of EGFR mutation status in NSCLC patients, which is promising to identify NSCLC patients sensitive to EGFR-TKI or ICI-treatments.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Aprendizado Profundo , Neoplasias Pulmonares/diagnóstico por imagem , Inibidores de Proteínas Quinases/administração & dosagem , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Intervalo Livre de Progressão
4.
Eur J Radiol ; 132: 109338, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33068840

RESUMO

OBJECTIVES: The aim of our study was to investigate the value of a simple metabolic heterogeneity parameter, COV (coefficient of variation), by 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the prognosis prediction of central lung cancer in early and locally advanced non-small-cell lung cancer (NSCLC). METHODS: Seventy-three patients with NSCLC manifesting as central lung cancer were included retrospectively, and we used the COV to evaluate metabolic heterogeneity. Univariate and multivariate analyses were used to evaluate the predictive value in terms of overall survival (OS) and progression-free survival (PFS). RESULT: For all 73 patients with pathologically confirmed NSCLC, 69.9 % had SCC, and 30.1 % had ADC or other types of NSCLC. The COV was a statistically significant factor in the univariate analysis for the OS rate. The optimal cut-off value was 23.1366, with sensitivity = 0.737 and specificity = 0.771. The COV values were dichotomized by this value and included with atelectasis in the Cox multivariate analysis. Both COV and atelectasis were independent risk factors for OS as follows: for COV (HR, 3.162, P = 0.0002), the 2-year OS rate was 62.5 % and 26.9 % in the low and high COV groups, respectively. For atelectasis (HR 2.047, P = 0.041), the 2-year OS rate was 30.6 % and 65.2 % in the groups with and without atelectasis, respectively (P = 0.017). For PFS, only COV (HR, 2.636, P = 0.001) was a significant predictor. The 2-year PFS rate was 29.7 % in the low COV group and 8% in the high COV group. CONCLUSION: The pre-treatment metabolic heterogeneity parameter COV is a simple and easy way to predict the OS and PFS of patients with NSCLC manifesting as central lung cancer. Therefore, COV plays an important role in prognostic risk classification in NSCLC. The presence of atelectasis could also be a risk factor for poor prognosis of OS.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/mortalidade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Idoso , Estudos de Avaliação como Assunto , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Taxa de Sobrevida
5.
PLoS One ; 15(10): e0236503, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33031375

RESUMO

BACKGROUND: The treatment for stage III non-small cell lung cancer (NSCLC) often involves multi-modality treatment. This retrospective study aimed to evaluate whether multidisciplinary team (MDT) discussion results in better patient survival. MATERIALS AND METHODS: MDT discussion was optional before February 2016 and was actively encouraged by the MDT committee beginning February 2016. We reviewed the medical charts and computer records of patients with stage III NSCLC between January 2013 and December 2018. RESULTS: A total of 515 patients were included. The median survival of all the patients was 33.9 months (M). The median survival of patients who were treated after MDT discussion was 41.2 M and that of patients treated without MDT discussion was 25.7 M (p = 0.018). The median survival of patients treated before February 2016 was 25.7 M and that of patients treated after February 2016 was 33.9 M (p = 0.003). The median survival of patients with stage IIIA tumors and those with stage IIIB tumors was 39.4 M and 25.7 M, respectively (p = 0.141). Multivariate analysis showed that MDT or not (p<0.001), T staging (p = 0.009), performance status (p<0.001), and surgery (p = 0.016) to be significant prognostic factors. CONCLUSION: The results of the study show that MDT discussion results in survival benefit in patients with stage III NSCLC. The MDT discussion, performance status, and if surgery was performed were independent prognostic factors for patients with stage III NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Comunicação Interdisciplinar , Neoplasias Pulmonares/mortalidade , Equipe de Assistência ao Paciente/estatística & dados numéricos , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
6.
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
7.
PLoS One ; 15(9): e0238358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881920

RESUMO

BACKGROUND: Mutations in STK11 (STK11m) and frequently co-occurring KRAS mutations (KRASm/STK11m) are associated with poor survival in metastatic NSCLC (mNSCLC) immuno-oncology trials. There are limited data regarding the prognostic significance of these mutations in a real-world setting. METHODS: This retrospective cohort study analyzed de-identified electronic medical records from the Flatiron Clinico-Genomic database to identify patients with mNSCLC who had initiated first-line immunotherapy (IO; alone or in combination) or chemotherapy under routine care between January 1, 2013 and June 30, 2017. The primary objectives were to assess the prevalence of STK11m and KRASm/STK11m and to determine associations of these mutations with overall and progression-free survival (OS, PFS). RESULTS: Of 2407 patients with mNSCLC, STK11m and KRASm/STK11m were present in 13.6% and 6.5% of patients, respectively. Worse OS outcomes were observed in patients with STK11m versus STK11wt mNSCLC receiving IO (first-line, HR [95% CI], 1.4 [0.9-2.3; p = 0.1]; second-line [subset of first-line cohort], HR, 1.6 [1.3-2.0; p = 0.0002]) or chemotherapy (first-line, HR, 1.4 [1.2-1.6; p < 0.0001]); PFS outcomes showed similar trends. KRASm/STK11m double mutations were associated with worse OS and PFS outcomes versus KRASwt/STK11wt with IO and chemotherapy, similar to the single mutation (STK11m vs STK11wt) findings. CONCLUSIONS: This large observational genomic study among patients receiving routine care highlights the negative prognostic impact of STK11m in patients with mNSCLC treated with IO or chemotherapy. These results complement previous clinical trial data and provide further evidence in the real world of a patient population that would benefit from new treatment options.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Proteínas Serina-Treonina Quinases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos , Taxa de Sobrevida
8.
N Engl J Med ; 383(18): 1711-1723, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-32955177

RESUMO

BACKGROUND: Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown. METHODS: In this double-blind, phase 3 trial, we randomly assigned patients with completely resected EGFR mutation-positive NSCLC in a 1:1 ratio to receive either osimertinib (80 mg once daily) or placebo for 3 years. The primary end point was disease-free survival among patients with stage II to IIIA disease (according to investigator assessment). The secondary end points included disease-free survival in the overall population of patients with stage IB to IIIA disease, overall survival, and safety. RESULTS: A total of 682 patients underwent randomization (339 to the osimertinib group and 343 to the placebo group). At 24 months, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% confidence interval [CI], 84 to 93) and 44% of those in the placebo group (95% CI, 37 to 51) were alive and disease-free (overall hazard ratio for disease recurrence or death, 0.17; 99.06% CI, 0.11 to 0.26; P<0.001). In the overall population, 89% of the patients in the osimertinib group (95% CI, 85 to 92) and 52% of those in the placebo group (95% CI, 46 to 58) were alive and disease-free at 24 months (overall hazard ratio for disease recurrence or death, 0.20; 99.12% CI, 0.14 to 0.30; P<0.001). At 24 months, 98% of the patients in the osimertinib group (95% CI, 95 to 99) and 85% of those in the placebo group (95% CI, 80 to 89) were alive and did not have central nervous system disease (overall hazard ratio for disease recurrence or death, 0.18; 95% CI, 0.10 to 0.33). Overall survival data were immature; 29 patients died (9 in the osimertinib group and 20 in the placebo group). No new safety concerns were noted. CONCLUSIONS: In patients with stage IB to IIIA EGFR mutation-positive NSCLC, disease-free survival was significantly longer among those who received osimertinib than among those who received placebo. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).


Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Acrilamidas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Pneumonectomia , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico
10.
J Cancer Res Ther ; 16(4): 757-763, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32930115

RESUMO

Purpose: To assess the survival outcomes and prognostic factors of young (≤45 years) Stage IIIB nonsmall cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). Materials and Methods: Medical records of 145 Stage IIIB NSCLC patients (≤45 years) who received 60-66 Gy thoracic radiotherapy and concurrent 1-3 cycles of cisplatin-based doublet chemotherapy were retrospectively evaluated. The primary endpoint was overall survival (OS), while locoregional progression-free survival (LRPFS), progression-free survival (PFS), and evaluation of potential prognostic factors constituted the secondary endpoints. Results: At median 21.6 months (range: 7.3-62.5) of follow-up, the median and 4-year survival estimates were 24.8 months and 24.2% for OS, 15.7 months and 18.9%, for LRPFS and 12.0 months and 11.2% for PFS, respectively. On univariate analyses, among all factors, the smaller tumor size (≤7.0 cm; P = 0.03), lower T-stage (T1-T2; P = 0.02), lower N-stage (N2; P = 0.01), absence of anemia before C-CRT (hemoglobin [Hb] ≥12 g/dL; P < 0.001), and lower/no pretreatment weight loss (WL ≤5%; P < 0.001) were found to be associated significantly with longer median OS durations, which also retained their independent significance on multivariate analyses, except for tumor size category. Conclusions: The encouraging median 24.8 months OS duration observed here in young NSCLC patients accords well with the results of recent landmark locally advanced NSCLC series without age stratification. Other than the well-established T and N stages, extra exhibit of superior OS in patients with initial Hb ≥12 g/dL and ≤5% WL levels suggests a noteworthy prognostic role for these two latter variables in the stratification of such patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Cisplatino/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Fatores Etários , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
11.
J Cancer Res Ther ; 16(4): 800-803, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32930121

RESUMO

Aims: Some studies investigated the association between nestin and the overall survival (OS) of nonsmall cell lung cancer (NSCLC). However, the results were conflicted and inconclusive. Therefore, we performed this meta-analysis to determine the association between nestin and OS of NSCLC. Materials and Methods: PubMed and EMBASE were searched to find relevant studies. The strength of the association was calculated with the hazard ratios (HRs) and respective 95% confidence intervals (CIs). Results: High expression of nestin was significantly associated with OS of NSCLC (HR = 2.09; 95% CI = 1.59-2.77). In the stratified analysis by race, we found that the expression of nestin was significantly associated with OS of NSCLC in Asians (HR = 3.02; 95% CI = 1.80-5.07) and Caucasians (HR = 1.81; 95% CI = 1.21-2.71). In addition, when we limited the meta-analysis to studies that controlled for clinical parameters, a significant association between nestin and OS of NSCLC remained (HR = 2.19; 95% CI = 1.54-3.11). A sensitivity analysis showed no substantial modification of the estimates after exclusion of individual studies. Conclusions: In conclusion, this meta-analysis suggested that high expression of nestin was significantly associated with OS of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Nestina/biossíntese , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Taxa de Sobrevida
12.
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
13.
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
14.
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
15.
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
16.
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
17.
Br J Radiol ; 93(1115): 20200645, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32822540

RESUMO

OBJECTIVE: To report our experience on stereotactic body radiotherapy (SBRT) in adrenal metastases from lung cancer. METHODS: 37 oligometastatic lung cancer patients with 38 adrenal metastases submitted to SBRT were retrospectively analyzed. SBRT was delivered by volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT). Primary study end point was local recurrence-free survival (LR-FS) and secondary end points were distant-progression free survival (d-PFS) and overall survival (OS). RESULTS: Median age was 67 years and primary tumor was non-small-cell lung cancer in 27 (73%) and small-cell lung cancer in 10 (27%) patients. Adrenal metastases were in the left side in 66% cases. Median prescribed dose was 30 Gy in 5 fractions for a median biologically equivalent dose (α/ß ratio 10 Gy, BED10) of 48 Gy. Most patients (62%) were submitted to SBRT alone, while the others (38%) received chemo-, immune- or target- therapies. Median follow-up was 10.5 months, median OS 16 months and median d-PFS 3 months. 27 (70%) patients obtained a local control with a median LR-FS of 32 months. LR-FS was significantly related to BED10 with a better LC with BED10 ≥72 Gy, 1- and 2 year LR-FS rates were 54.1±11.6% and 45±12.7% vs 100 and 100% for BED ≤59.5 Gy and BED ≥72 Gy, respectively (p = 0.05). There was no severe toxicity. CONCLUSION: SBRT was effective and safe in lung cancer adrenal metastases. A dose-response relationship was found between BED10 >72 Gy and better local control. No significant toxicity was registered thanks to the respect of dose constraints and suspension of chemo- and target-therapies. ADVANCES IN KNOWLEDGE: SBRT with a BED10 >72 Gy is an effective treatment for adrenal oligometastatic lung cancer patients.


Assuntos
Neoplasias das Glândulas Suprarrenais/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/patologia , Radiocirurgia/métodos , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Terapia Combinada/métodos , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/secundário
18.
PLoS One ; 15(8): e0237790, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32810185

RESUMO

This study determined the frequency and factors associated with EGFR testing rates and erlotinib treatment as well as associated survival outcomes in patients with non small cell lung cancer in Kentucky. Data from the Kentucky Cancer Registry (KCR) linked with health claims from Medicaid, Medicare and private insurance groups were evaluated. EGFR testing and erlotinib prescribing were identified using ICD-9 procedure codes and national drug codes in claims, respectively. Logistic regression analysis was performed to determine factors associated with EGFR testing and erlotinib prescribing. Cox-regression analysis was performed to determine factors associated with survival. EGFR mutation testing rates rose from 0.1% to 10.6% over the evaluated period while erlotinib use ranged from 3.4% to 5.4%. Factors associated with no EGFR testing were older age, male gender, enrollment in Medicaid or Medicare, smoking, and geographic region. Factors associated with not receiving erlotinib included older age, male gender, enrollment in Medicare or Medicaid, and living in moderate to high poverty. Survival analysis demonstrated EGFR testing or erlotinib use was associated with a higher likelihood of survival. EGFR testing and erlotinib prescribing were slow to be implemented in our predominantly rural state. While population-level factors likely contributed, patient factors, including geographic location (areas with high poverty rates and rural regions) and insurance type, were associated with lack of use, highlighting rural disparities in the implementation of cancer precision medicine.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/uso terapêutico , Testes Genéticos/estatística & dados numéricos , Neoplasias Pulmonares/tratamento farmacológico , Demandas Administrativas em Assistência à Saúde/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Análise Mutacional de DNA/economia , Análise Mutacional de DNA/estatística & dados numéricos , Prescrições de Medicamentos/economia , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/economia , Uso de Medicamentos/estatística & dados numéricos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Testes Genéticos/economia , Disparidades em Assistência à Saúde/economia , Humanos , Kentucky/epidemiologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Medicaid/economia , Medicaid/estatística & dados numéricos , Medicare/economia , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Mutação , Pobreza/estatística & dados numéricos , Medicina de Precisão/economia , Medicina de Precisão/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Fatores Sexuais , Análise de Sobrevida , Estados Unidos , Adulto Jovem
19.
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
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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