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1.
Medicine (Baltimore) ; 99(9): e19314, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32118758

RESUMEN

BACKGROUND: Ruling out distant metastases, non-small cell lung cancer (NSCLC)treatment depends on the results of mediastinal node staging (N staging). Several diagnostic methods play central roles in mediastinal N staging. This study is intended to evaluate the existing diagnostic methods and report quality, and to search for the best method for staging mediastinal lymph nodes. METHODS: We searched PubMed, Embase, and the Cochrane Library to identify relevant studies, including randomized controlled trials and retrospective studies. These studies report the application of computed tomography, positron emission tomography-computed tomography, magnetic resonance imaging, endobronchial ultrasound, and mediastinoscopy in the diagnosis of mediastinal lymph node staging of NSCLC. The quality of the literature was assessed using the Quality Assessment of Diagnostic Accuracy Study 2. The true positive, false positive, true negative, and false negative of each study was extracted. The corresponding sensitivity, specificity, and other indicators were calculated and the Summary Receiver Operating curve was established. Then, head-to-head and indirect comparison meta-analyses will be conducted. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will provide basis for mediastinal lymph node staging of non-small cell lung cancer. PROSPERO REGISTRATION NUMBER: CRD42019145667.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Diagnóstico por Imagen/normas , Ganglios Linfáticos/fisiopatología , Estadificación de Neoplasias/normas , Anciano , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Protocolos Clínicos , Diagnóstico por Imagen/métodos , Endoscopía/métodos , Endoscopía/normas , Femenino , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/normas , Masculino , Mediastinoscopía/métodos , Mediastinoscopía/normas , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/normas , Tomografía Computarizada por Rayos X/métodos , Tomografía Computarizada por Rayos X/normas , Ultrasonografía/métodos , Ultrasonografía/normas
2.
Medicine (Baltimore) ; 99(11): e19087, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32176035

RESUMEN

Identify the prevalence of postoperative anxiety and depression as well as their correlations with clinical features and survival profiles in non-small-cell lung cancer (NSCLC) patients who underwent resection.Four hundred NSCLC patients who underwent resection were recruited, and their anxiety and depression were assessed by hospital anxiety and depression scale (HADS) at discharge after surgery. Besides, 480 healthy controls (HCs) were also enrolled and assessed by HADS.The HADS-Anxiety score of NSCLC patients (7.8 ±â€Š3.9) was greatly higher than that of HCs (4.8 ±â€Š2.7), and the anxiety prevalence of NSCLC patients (49.6%) were dramatically increased compared with HCs (13.8%). Furthermore, the HADS-Depression score (7.2 ±â€Š3.6) of NSCLC patients was considerably increased compared with HCs (4.2 ±â€Š2.6), and the depression prevalence of NSCLC patients (38.3%) was significantly raised compared with HCs (10.0%). Besides, anxiety correlated with gender, marital status, hypertension, diabetes, pathological differentiation, tumor size, lymph node metastasis, TNM stage and carcinoembryonic antigen level, meanwhile, depression correlated with marital status, employment status before surgery, diabetes, pathological differentiation, and TNM stage in NSCLC patients. Additionally, the anxiety and depression predicted shorter disease-free survival in NSCLC patients. And the anxiety predicted worse overall survival (OS), while no association of depression with OS was observed in NSCLC patients.Post-operative anxiety and depression are highly prevalent and implicated in the ongoing care and prognosis prediction in NSCLC patients who underwent resection.


Asunto(s)
Ansiedad/etiología , Carcinoma de Pulmón de Células no Pequeñas/psicología , Depresión/etiología , Neoplasias Pulmonares/psicología , Ansiedad/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Estudios de Casos y Controles , China/epidemiología , Depresión/epidemiología , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Prevalencia , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Factores Sexuales
3.
Medicine (Baltimore) ; 99(8): e19097, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32080083

RESUMEN

Liquid biopsy is an emerging technique for noninvasive detection of various cancers. Majority of liquid biopsy tests still, however, use solitary type of biomarkers with unsatisfactory sensitivity and specificity. To this end, a combined approach of circulating tumor cells (CTCs) and salivary mRNA biomarkers was evaluated for discriminating non-small-cell lung cancer (NSCLC) from healthy controls.Our study included a discovery phase to find multiple biomarkers, and an independent validation phase to confirm the applicability of the selected biomarkers. In the discovery phase, CTC level in blood and 5 mRNA biomarkers in saliva (i.e., CCNI, Epidermal growth factor receptor [EGFR], FGF19, FRS2, and GREB1) were measured for 140 NSCLC patients and 140 healthy controls, followed by developing a predictive model. Next, this panel of biomarkers was applied to another patient cohort consisted of 60 patients with NSCLC and 60 healthy controls in the validation phase.We found that our novel biomarker panel could differentiate patients with NSCLC from healthy controls with high sensitivity (92.1%) and high specificity (92.9%) in the discovery phase. In the validation phase, we achieved sensitivity of 88.3% and specificity of 90.0%.To our best knowledge, it is the first time that a combined use of CTC and salivary mRNA biomarkers were applied for noninvasive detection of NSCLC.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Células Neoplásicas Circulantes/metabolismo , ARN Mensajero/metabolismo , Saliva/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Ciclina I/metabolismo , Receptores ErbB/metabolismo , Femenino , Factores de Crecimiento de Fibroblastos/metabolismo , Humanos , Biopsia Líquida/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Células Neoplásicas Circulantes/patología , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad
4.
Biosci Trends ; 14(1): 48-55, 2020 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-32023563

RESUMEN

The aim of this multicentric retrospective study is to evaluate the predictive and prognostic performance of neutrophil to lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and their dynamics in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab as a second line. Patients with metastatic NSCLC (n = 119), whose tumors expressed programmed death-ligand 1 (PD-L1) ≥ 1%, were retrospectively analyzed between Apr 2017 and Apr 2019. All patients received platinum-containing chemotherapy as a first line treatment. Pre-treatment NLR was calculated by dividing the number of neutrophils by the number of lymphocytes in peripheral blood before the first pembrolizumab infusion. Progression free survival (PFS) and overall survival (OS) was compared by Kaplan-Meier method and Cox Proportional Hazard model. Patients with NLR > 5 before immunotherapy showed significantly shorter mean PFS of 6.86 months (95% CI: 5.81-7.90) as compared to those with NLR ≤ 5 of 18.82 months (95% CI: 15.87-21.78) (long rank test p < 0.001). Furthermore in the multivariate analysis, only NLR > 5 was an independent predictive factor for shorter PFS (HR: 4.47, 95% CI: 2.20-9.07, p < 0.001). In multivariate analysis, presence of bone metastases (HR: 2.08, 95% CI: 1.10-4.94, p = 0.030), NLR > 5 before chemotherapy (HR: 8.09, 95% CI: 2.35-27.81, p = 0.001) and high PLR before chemotherapy (HR: 2.81, 95% CI: 1.13-6.97, p = 0.025) were found to be independent negative prognostic factors for poor OS. Our data suggests that NLR ≤ 5 is a potential predictive marker, which may identify patients appropriate for immunotherapy as a second line treatment.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Linfocitos/citología , Neutrófilos/citología , Anciano , Antígeno B7-H1 , Biomarcadores , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Femenino , Humanos , Inmunoterapia , Estimación de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Compuestos de Platino/uso terapéutico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia
5.
Anticancer Res ; 40(2): 957-964, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32014940

RESUMEN

BACKGROUND/AIM: To describe real clinical outcomes when using systemic therapy to treat non-small cell lung cancer (NSCLC) patients who have anaplastic lymphoma kinase (ALK) fusion gene mutation. PATIENTS AND METHODS: We performed a retrospective chart review from April 2008 to March 2019 sourced from 16 medical institutes that cover a population of three million people. RESULTS: There were 129 ALK rearranged NSCLC patients. Among them, 103 patients including 40 recurrent disease cases received ALK-tyrosine kinase inhibitors (TKI) and chemotherapy. Our treatment results were comparable to previously reported clinical trials and clinical practice studies. First-line alectinib, treatment sequence of ALK-TKI followed by another ALK-TKI, and pemetrexed-containing chemotherapy contributed to the outcome of treatment. CONCLUSION: By arrangement of treatment such as treatment sequence of ALK-TKI and chemotherapy regimen, it might be possible to obtain a treatment outcome almost equivalent to those of clinical trials even in real clinical practice.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/etiología , Reordenamiento Génico , Neoplasias Pulmonares/etiología , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/terapia , Manejo de la Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Proteínas de Fusión Oncogénica/genética , Pronóstico , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Carga Tumoral
7.
Cancer Invest ; 38(2): 102-112, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31977287

RESUMEN

Background: Patient survival is not optimal for non-small cell lung cancer (NSCLC) patients, recurrence rate is high, and hence, early detection is crucial to increase the patient's survival. Gene-cancer mapping intends to discover associated genes with cancers and due to advances in high-throughput genotyping, screening for disease loci on a genome-wide scale is now possible. DNA copy numbers can potentially be used to identify cancer from normal cells in early detection of cancer.Methods: We use a nonlinear clustering method, so-called kernel K-means to separate cancer from normal samples. Kernel K-means is applied to the copy numbers obtained for each chromosome to cluster 63 paired cancer-blood samples (total of 126 samples) into two groups. Clustering performance is evaluated using true and false-positive rates, true and false-negative rates, and a nonlinear criterion, normalized mutual information (NMI).Results: Copy numbers of paired cancer-blood samples for 63 NSCLC patients are used in this study. Kernel K-means was applied to cluster 126 samples in two groups using copy numbers on each chromosome separately. The clustering results for 22 chromosomes are evaluated and discriminant power of them in identifying cancer is computed. We identified the top five and bottom five chromosomes based on their discriminant power.Conclusions: The results reveal high discriminant power of chromosomes 8, 5, 1, 3, and 19 for identifying cancer with the highest sensitivity of 75% yielded by chromosome 5. Bottom 5 chromosomes 9, 6, 4, 13, and 21 show low discriminant power with the accuracy of below 54% where true cancer and normal samples are grouped into substantially overlapping groups using copy numbers. This indicates the similarities of copy numbers obtained for cancer and normal samples on these chromosomes.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Variaciones en el Número de Copia de ADN , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Análisis por Conglomerados , Análisis Discriminante , Detección Precóz del Cáncer/métodos , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Recurrencia Local de Neoplasia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
8.
Oncology ; 98(1): 23-28, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31494653

RESUMEN

BACKGROUND: Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), is effective against EGFR-mutated non-small cell lung carcinoma resistant to first- or second-generation EGFR-TKIs in patients in whom an EGFR T790M mutation has been detected. Detection of the T790M mutation using circulating tumor DNA (ctDNA) is less invasive than a tissue re-biopsy, including a transbronchial lung biopsy; however, the prognostic implications of the T790M mutation in ctDNA have not been fully elucidated. METHODS: We retrospectively reviewed the clinical features of non-small cell lung carcinoma patients in whom an EGFR T790M mutation had been detected at our hospital and assessed the clinical outcomes of osimertinib for these patients in terms of detection sites. RESULTS: An EGFR T790M mutation was detected in 32 non-small cell lung carcinoma patients, of whom 21 (65.6%) underwent osimertinib treatment after detection of the mutation. The mutation was detected using plasma samples in 10 patients (47.6%; liquid biopsy group), while it was detected using tissue samples in 11 patients (52.4%; tissue biopsy group). Liver and bone metastases were more frequently observed in patients in the liquid biopsy group than in the tissue biopsy group (30.0 vs. 0% and 60.0 vs. 18.2%, respectively). The median progression-free survival time was significantly shorter in the liquid biopsy group (132.0 days) than in the tissue biopsy group (682.0 days). The median overall survival time in the liquid biopsy group was 376.0 days, whereas that in the tissue biopsy group was not reached during our observation period. CONCLUSIONS: Non-small cell lung carcinoma patients in whom an EGFR T790M mutation was detected in plasma samples demonstrated a poorer response to osimertinib than those in whom the mutation was detected in tissue specimens.


Asunto(s)
Sustitución de Aminoácidos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , ADN Tumoral Circulante , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mutación , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Receptores ErbB/genética , Femenino , Humanos , Biopsia Líquida , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
9.
J Oncol Pharm Pract ; 26(1): 13-22, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30832554

RESUMEN

PURPOSE: To describe the outcomes of a pharmacist-led multi-center, collaborative patient education and proactive adverse event management program in a community-based oncology setting. METHODS: Patients with EGFR mutation-positive (EGFRm+) non-small cell lung cancer, newly prescribed with oral afatinib, and monitored as part of the Florida Cancer Specialists patient management program, were included in a retrospective, observational analysis. During follow-up, data were collected on adverse event frequency, and changes in afatinib dosing. Data analyses were descriptive and exploratory in nature. RESULTS: The mean age of the 123 patients included in the analysis was 69 years, and 78% were female. At the time of the analysis, 3 patients had discontinued before receiving treatment, 89 patients had discontinued afatinib treatment, and 31 patients were continuing to receive afatinib treatment. The most common afatinib-related adverse events were diarrhea (85%), rash/skin reactions (58%), stomatitis/mucositis (19%), and paronychia (16%). Overall, 13% of patients discontinued due to afatinib-related adverse events. The median duration of treatment was 4 months in patients who discontinued due to adverse events, 6 months in those who discontinued for other reasons, and 18 months in those who were continuing to receive therapy. Afatinib dose-reductions were more frequent in patients continuing treatment versus those who discontinued due to adverse events (77% vs. 42%, respectively). CONCLUSIONS: Findings suggest that adverse events in patients with EGFRm + non-small cell lung cancer receiving afatinib can be successfully managed in a community-based, real-world setting with the help of collaborative pharmacist-led patient education, adverse event monitoring, and continuous support.


Asunto(s)
Afatinib/efectos adversos , Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Educación del Paciente como Asunto/tendencias , Farmacéuticos/tendencias , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Servicios Comunitarios de Farmacia/tendencias , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/terapia , Receptores ErbB/genética , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto/métodos , Relaciones Profesional-Paciente , Estudios Retrospectivos
10.
Support Care Cancer ; 28(1): 389-394, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31055666

RESUMEN

PURPOSE: Low skeletal muscle mass has been associated with poor prognosis in patients with advanced lung cancer. However, little is known about the relationship between skeletal muscle mass and overall survival in patients with bone metastases from lung cancer. The objective of the present study was to evaluate the prognostic value of low trunk muscle mass in predicting overall survival in these patients. METHODS: The data from 198 patients who were diagnosed with bone metastases from lung cancer from April 2009 to May 2017 were retrospectively reviewed. The areas of the psoas and paravertebral muscles were measured at the level of the third lumbar vertebra on computed tomography scans taken at the time nearest to the diagnosis of bone metastasis. Muscle area was evaluated for male and female cohorts separately using different cutoff points. Cox proportional hazards analysis was performed to evaluate the factors independently associated with overall survival. RESULTS: The overall survival of patients in the lowest quartile for psoas muscle area or paravertebral muscle area was significantly shorter than that of patients above the 25th percentile for muscle area (p < 0.001). Multivariate analyses showed that paravertebral muscle mass (hazard ratio, 1.73; 95% confidence interval, 1.17-2.56; p = 0.006), epidermal growth factor receptor-targeted therapy, and performance status were independent prognostic factors. CONCLUSIONS: Low paravertebral muscle mass was associated with shorter survival, independently of known prognostic factors.


Asunto(s)
Neoplasias Óseas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Músculo Esquelético/patología , Sarcopenia/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/mortalidad , Neoplasias Óseas/secundario , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Sarcopenia/mortalidad , Sarcopenia/patología , Análisis de Supervivencia , Tomografía Computarizada por Rayos X/métodos
11.
Pol J Pathol ; 70(3): 183-188, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31820861

RESUMEN

CD63 has been suggested to participate in tumorigenesis, invasion, and metastasis. In this study, we aimed to investigate the prognostic significance of CD63 expression in non-small cell lung cancer (NSCLC). CD63 expression was evaluated in 133 cases of NSCLC via immunohistochemical staining using tissue microarray blocks. We assessed the relationship between CD63 expression and clinicopathological characteristics, as well as the prognostic significance of CD63 expression in NSCLC. CD63 expression was significantly correlated with patient gender (p < 0.001), smoking history (p = 0.020), histologic type (p < 0.001), tumour stage (p = 0.016), lymph node metastasis (p = 0.034), and TNM stage (p = 0.007). A multivariate Cox proportional hazards regression analysis determined low CD63 expression to be an independent factor for unfavourable disease-free survival (DFS) (HR = 2.043, 95% CI: 1.035-4.035, p = 0.040), and Kaplan-Meier analysis indicated that the low CD63 expression group showed significantly lower DFS than the high CD63 expression group of patients with NSCLC (p = 0.019). Low CD63 expression might be an unfavourable prognostic factor in patients with NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Tetraspanina 30/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Supervivencia sin Enfermedad , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales
12.
Pol J Pathol ; 70(3): 189-197, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31820862

RESUMEN

Large tumor suppressor kinase 2 (LATS2) is a core component in the Hippo signaling pathway, and it functions as a tumor suppressor associated with tumor cell proliferation and apoptosis. The purpose of this study is to explore LATS2 expression and its clinicopathological significance in non-small cell lung cancer (NSCLC). We examined LATS2 protein expression by immunohistochemistry in 184 resected NSCLC specimens using tissue microarrays. Low LATS2 expression was significantly related to disease recurrence (p = 0.047). In survival analysis, the low LATS2 expression group showed a statistically poorer overall survival (OS) (p = 0.004) and disease-free survival (DFS) (p = 0.014) than the high expression group. In multivariate analysis, downregulated LATS2 expression in NSCLC could be an independent prognostic factor of poor OS and DFS. Furthermore, we evaluated the prognostic significance of LATS2 expression in two major NSCLC subtypes, squamous cell carcinoma and adenocarcinoma. The low LATS2 expression group showed worse prognosis than the high LATS2 expression group (OS [p = 0.144] and DFS [p = 0.022] in squamous cell carcinoma and OS [p = 0.045] and DFS [p = 0.271] in adenocarcinoma). We demonstrated that downregulated LATS2 expression may predict aggressive biologic behavior and a worse prognosis in NSCLC and we also suggested the possibility of LATS2 as a therapeutic target in both squamous cell carcinoma and adenocarcinoma.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Pronóstico
13.
Medicine (Baltimore) ; 98(50): e17814, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31852062

RESUMEN

The purpose of our research was to evaluate diagnostic performance of serum microRNA-135a (miR-135a) in non-small cell lung cancer (NSCLC).Quantitative real time-polymerase chain reaction was employed to detect the expression serum of miR-135a in NSCLC patients and controls. The influence of serum miR-135a level on clinical characteristics of NSCLC patients was explored through the Chi-square test. Serum carcinoembryonic antigen (CEA) level was estimated via enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve was plotted to elucidate diagnostic roles of serum miR-135a and CEA in NSCLC.The expression level of serum miR-135a was significantly lower in NSCLC patients than in healthy controls (0.40 ±â€Š0.29 vs 1.00 ±â€Š0.40, P < .001). Moreover, miR-135a expression was related to lymph node metastasis (P = .021), tumor differentiation (P = .020), and tumor node metastasis stage (P = .031). ROC curve showed serum miR-135a level could discriminate NSCLC patients from healthy controls (P < .0001) with a corresponding cutoff value of 0.665, and a sensitivity and specificity of 81.3% and 83.1%, respectively. The area under the curve was 0.888. In diagnosis analysis on the combination of miR-135a and CEA, when its specificity was maintained at 90%, diagnosis cut-off point reached 0.678.Serum miR-135a level is significantly downregulated in NSCLC and serves as a potential diagnostic biomarker for the disease.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , MicroARNs/sangre , Estadificación de Neoplasias/métodos , Anciano , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Neoplasias Pulmonares/sangre , Masculino , Persona de Mediana Edad , ARN Neoplásico/genética , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa
14.
Medicine (Baltimore) ; 98(50): e18208, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31852077

RESUMEN

In non-small cell lung cancer (NSCLC) patients, the recommended minimum requirement for an endoscopy-based mediastinal staging procedure is sampling the largest lymph node (LN) in right and left inferior paratracheal, and subcarinal stations. We aimed to analyze the percentage of cases where the largest LN in each mediastinal station was malignant in a cohort of NSCLC patients with mediastinal metastases diagnosed in the lymphadenectomy specimen. Furthermore, we investigated the sensitivity of a preoperative staging procedure in a hypothetical scenario where only the largest LN of each station would have been sampled.Prospective data of patients with mediastinal nodal metastases diagnosed in the lymphadenectomy specimens were retrospectively analyzed. The long-axis diameter of the maximal cut surface of all LNs was measured on hematoxylin and eosin-stained sections.Seven hundred seventy five patients underwent operation and 49 (6%) with mediastinal nodal disease were included. A total of 713 LNs were resected and 119 were involved. Sixty seven nodal stations revealed malignant LNs: in these, the largest LN was malignant in 39 (58%). In a "per patient" analysis, a preoperative staging procedure that sampled only the largest LN would have attained a sensitivity of 0.67; and if the largest and the second largest were sampled, sensitivity would be 0.87.In patients with NSCLC, nodal size ranking is not reliable enough to predict malignancy. In clinical practice, regardless of the preoperative staging method, systematic thorough sampling of all visible LNs is to be recommended over selective random samplings.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Mediastinoscopía/métodos , Estadificación de Neoplasias , Cirugía Torácica Asistida por Video/métodos , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/cirugía , Metástasis Linfática , Masculino , Mediastino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Tiempo
15.
Medicine (Baltimore) ; 98(50): e18310, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31852114

RESUMEN

PURPOSE: We designed the study to investigate the incidence risk of Programmed Cell Death-1 (PD-1) or Ligand 1 (PD-L1) inhibitor-related endocrine dysfunction in patients with lung cancer. METHOD: All the data were collected by 1 primary reviewer and then independently reviewed by 2 secondary reviewers according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM) guidelines. Incidence risk of all-grade and grade 3-5 PD-1/PD-L1 inhibitors related endocrine dysfunction in patients with lung cancer were taken into account. RESULTS: Overall, 12 clinical trials comprising 6108 patients were identified in this systematic review and meta-analysis. The incidence risk of hypothyroidism, hyperthyroidism and adrenal insufficiency was higher in NSCLC patients receiving combination treatments. The incidence rate of all-grade of hypothyroidism was lower in PD-1/PD-L1 inhibitor subgroup compared to chemotherapy (OR = 22.62, 95%CI:9.79-52.25), while the similar result was seen in another treatment regimen (PD-1 + platinum-based chemotherapy vs platinum-based chemotherapy) (OR = 2.93, 95%CI: [2.08, 4.11). The different result can be seen in the group related to the other treatment regimen (1PD-1/PD-L1 inhibitor vs 2 PD-1/PD-L1 inhibitors) (OR = 0.40, 95%CI:0.21-0.76). All the results of the above analysis were considered to be statistical significant. Similar result could also be seen in meta-analysis related to hyperthyroidism and adrenal insufficiency. CONCLUSION: The incidence risk of endocrine dysfunctions, including hypothyroidism, hyperthyroidism and adrenal insufficiency, were higher for PD-1/PD-L1 inhibitors group.


Asunto(s)
Antígeno B7-H1/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Enfermedades del Sistema Endocrino/sangre , Neoplasias Pulmonares/sangre , Nivolumab/uso terapéutico , Receptor de Muerte Celular Programada 1/sangre , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Enfermedades del Sistema Endocrino/epidemiología , Enfermedades del Sistema Endocrino/etiología , Salud Global , Humanos , Incidencia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico
16.
Zhonghua Zhong Liu Za Zhi ; 41(12): 881-890, 2019 Dec 23.
Artículo en Chino | MEDLINE | ID: mdl-31874543

RESUMEN

Lung cancer is the most common cancer and the leading cause of cancer death in China, with 733 thousands estimated new lung cancer cases and 610 thousands deaths in 2015. In the pathological type of lung cancer, non-small cell lung cancer (NSCLC) accounts for 80%~85%, and 30% of NSCLC patients have already reached stage Ⅲ at diagnosis, who have lost the optimal opportunity for surgical treatment. Stage Ⅲ NSCLC is highly heterogeneous, the 5-year survival rates of stage ⅢA, ⅢB and ⅢC NSCLC are 36%, 26% and 13%, respectively. For the great complexity of making decisions in the clinical practice of stage Ⅲ NSCLC, the experts of this consensus group combine the latest clinical research results and cutting-edge multidisciplinary concepts, conduct in-depth and detailed discussions on the hot issues and controversies in the diagnosis, treatment and follow-up surveillance of stage Ⅲ NSCLC. Chinese Anti-Cancer Association and Committee of Lung Cancer Society jointly publish this consensus to provide guidance for Chinese clinicians.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , China/epidemiología , Consenso , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Sociedades Médicas , Tasa de Supervivencia
17.
Semin Oncol ; 46(4-5): 327-333, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31708233

RESUMEN

BACKGROUND: There is wide interest in developing prognostic models in non-small-cell lung cancer (NSCLC) due to the heterogeneity of the disease. Models developed at other healthcare institutions may not be directly applicable for patients treated at the Department of Veterans Affairs (VA). External validation of a candidate prognostic model among VA patients would be crucial before it can be implemented to aid clinical decision-making. METHODS: A prognostic model for mortality developed in the Military Health System (MHS) was applied to data from the VA Precision Oncology Data Repository (VA-PODR), which is available to researchers inside and outside the VA at the Veterans Precision Oncology Data Commons (VPODC). Measures of discrimination and calibration were calculated for the MHS model. The MHS model was also refitted in VA-PODR data using the same risk factors to compare the effect of specific factors and predictive performance when the model is developed using VA data. RESULTS: Time-dependent AUC of the MHS prognostic model was 0.788, 0.806, 0.780, and 0.779 for predicting survival at 1, 2, 3, and 5 years following diagnosis, respectively. Significant discrepancies were found between predicted and observed rates of survival, particularly for later years. When the model is refit in VA-PODR data, it achieved cross-validated AUCs of 0.739, 0.773, 0.769, and 0.807 at the same time points, and discrepancies between predicted and observed survival were reduced. CONCLUSIONS: Validation of the MHS prognostic model in VA-PODR demonstrates that its discrimination remains strong when applied to VA patients. Nevertheless, further calibration to VA data may be needed to improve its risk estimation performance. This study highlights the utility of VA-PODR and the VPODC as a national resource for developing analytic tools that are well adapted to the Veteran population.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Salud de los Veteranos/estadística & datos numéricos , Veteranos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Oncología Médica , Persona de Mediana Edad , Mortalidad , Medicina de Precisión , Pronóstico , Curva ROC , Reproducibilidad de los Resultados , Factores de Riesgo , Estados Unidos/epidemiología
18.
Zhonghua Zhong Liu Za Zhi ; 41(11): 826-830, 2019 Nov 23.
Artículo en Chino | MEDLINE | ID: mdl-31770849

RESUMEN

Objective: To investigate the expression of fragile-site associated tumor suppressor (FATS) in non-small cell lung cancer and its relationship with clinicopathological features and prognosis. Methods: A total of 140 non-small cell lung cancer (NSCLC) cases and 30 adjacent normal tissues were used to detect the expression level of FATS protein, and to analyze the relationship of FATS protein expression and clinicopathological features and prognosis of NSCLC. Results: Western blot showed that the expression of FATS in adjacent normal tissues was significantly higher than that in non-small cell lung cancer tissues. The results of immunohistochemistry showed that the high expression rate of FATS in 140 cases of NSCLC was 40.0%, and the high expression rate of FATS in 30 cases of adjacent tissues was 73.3%. The difference was statistically significant (P=0.01). Further analysis showed that the TNM stage (P=0.044) and lymph node metastasis (P=0.022) were significant difference between FATS high expression group and low expression group. The 6-year overall survival (OS) rates of NSCLC patients with FATS high-expression and low-expression were 57.1% and 23.8%, respectively, and the 6-year disease-free survival (DFS) rates were 53.6% and 21.4%, respectively, with statistically significant differences (P=0.001). In Cox multivariate analysis, we found gender (HR=1.658, P=0.028; HR=1.684, P=0.023), TNM staging (HR=2.327, P=0.019; HR=2.332, P=0.013) and FATS expression (HR=0.532, P=0.010; HR=0.538, P=0.009) were independent prognostic factors for both OS and DFS of NSCLC patients. Conclusions: The expression of FATS protein is associated with the development and is an independent prognostic factor of NSCLC patients. The detection of FATS protein is expected to be a new biomarker for evaluating the prognosis of NSCLC patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Proteínas del Citoesqueleto/genética , Neoplasias Pulmonares/genética , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Estadificación de Neoplasias , Pronóstico
19.
Zhonghua Bing Li Xue Za Zhi ; 48(11): 867-872, 2019 Nov 08.
Artículo en Chino | MEDLINE | ID: mdl-31775436

RESUMEN

Objective: To evaluate the concordance of PD-L1 expression in various tissues using antibodies 28-8 and SP263 on their respective detection platforms. Methods: Three hundred seventy four specimens of surgical resection of pulmonary diseases in the First Affiliated Hospital of Nanjing Medical University from January 1, 2012 to January 31, 2017 were collected. Totally 374 cases were tested for PD-L1 expression using the two antibodies, 28-8 and SP263, by respective detection platforms (Dako and Ventana). Finally, 336 cases were used for further evaluation, and the results were statistically analyzed for concordance. Results: For non-small cell lung carcinoma (NSCLC), the positive rate of PD-L1 was 57.5% (177/308) using SP263, and 57.5% (177/308) using 28-8 antibody. The correlation coefficient was 0.97 (P<0.01). The positive rate of both benign lung diseases and paracancerous tissues was about 10.7% (3/28), and the positive concordance rate was 100.0%. The distribution of both antibodies was also relatively consistent. Conclusions: The expression levels of 28-8 and SP263 antibodies in NSCLC and other tissues are relatively consistent, suggesting both antibodies may be complementary and substitute for each other, which may be useful in guiding clinical management.


Asunto(s)
Antígeno B7-H1/análisis , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Anticuerpos , Biomarcadores de Tumor/análisis , Humanos , Inmunohistoquímica
20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(9): 838-842, 2019 Sep.
Artículo en Chino | MEDLINE | ID: mdl-31750828

RESUMEN

Objective To explore the preliminary application of metabonomics in the qualitative diagnosis of non-small cell lung cancer (NSCLC). Methods According to the pathological type, 201 patients with NSCLC were divided into squamous cell carcinoma (SCC) group (n=71) and adenocarcinoma (AC) group (n=130). Immunohistochemistry was used to detect the expression of ki67, cytokeratin 5/6 (CK5/6) and CK7. Ultra-high performance liquid chromatography-time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was used to detect serum metabolomics. Results SCC group showed typical SCC structure; ki67 proliferation index was 21.9%; CK5/6 expression was positive; CK7 expression was negative or weakly positive. The typical adenoid structure was found in the AC group; the proliferation index of ki67 was 17.6%; CK7 was positive; and CK5/6 was negative or weakly positive. UPLC-Q/TOF-MS screened 28 different metabolites, of which 6 were the most significant ones: L-leucine, carnitine, C16 sphinganine, 13, 16, 19-docosatrienoic acie (DA), LysoPE (18:2/0:0), PC (20:4/P-16:0). These metabolites had good diagnostic value, among which L-Leucine had the highest specificity and LysoPE had the highest sensitivity. Conclusion Metabolomic analysis of lung SCC and AC provides a new index for the differential diagnosis of NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Metabolómica , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/metabolismo
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