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1.
Anticancer Res ; 40(2): 1007-1014, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32014946

RESUMEN

BACKGROUND/AIM: Myeloid cell leukemia-1 (MCL-1) is a member of the B-cell lymphoma-2 (Bcl-2) family of proteins, which regulate the intrinsic (mitochondrial) apoptotic cascade. MCL-1 inhibits apoptosis, which may be associated with resistance to cancer therapy. Therefore, in this study, the clinical role of MCL-1 in non-small cell lung cancer (NSCLC) was explored. PATIENTS AND METHODS: This retrospective study included 80 patients with stage 1-3A NSCLC, who underwent surgery without preoperative treatment between 2010 and 2011. MCL-1 expression and Ki-67 index were determined via immunohistochemical staining. Apoptotic index (AI) was determined via terminal deoxynucleotidyl transferase dUTP nick end labeling. RESULTS: The receiver operating characteristic curve analysis (area under curve=0.6785) revealed that MCL-1 expression in 30.0% of the NSCLC tumor cells was a significant cut-off for predicting prognosis. Tumors were considered MCL-1-positive if staining was observed in >30% of the cells. Thirty-six tumors (45.0%) were MCL-1-positive. However, there were no significant differences between MCL-1 expression and clinical variables. AI was lower in MCL-1-positive (2.2±3.6%) than in MCL-1-negative (5.2±7.9%) tumors, although the difference was not significant (p=0.1080). The Ki-67 index was significantly higher in MCL-1-positive than in MCL-1-negative tumors (18.0% vs. 3.0%; p<0.001). Five-year survival rate was significantly worse in patients with MCL-1-positive tumors (68.3%) than in those with MCL-1-negative tumors (93.1%, p=0.0057). Univariate [hazard ratio (HR)=5.041, p=0.0013], and multivariate analyses revealed that MCL-1 expression was a significant prognostic factor (HR=3.983, p=0.0411). CONCLUSION: MCL-1 expression in NSCLC cells correlated inversely with AI and positively with Ki-67 index. MCL-1 may serve as a potential prognostic biomarker and a novel therapeutic target in NSCLC.


Asunto(s)
Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Expresión Génica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/genética , Adulto , Anciano , Apoptosis/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC
2.
Medicine (Baltimore) ; 99(5): e18959, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32000421

RESUMEN

The outcomes of minimally invasive thoracoscopic pulmonary segmentectomy for non-small cell lung cancer (NSCLC) still need to be defined. This study aimed to investigate the feasibility and effectiveness of thoracoscopic pulmonary segmentectomy in patients with early peripheral NSCLC.This was a retrospective study of patients with early peripheral NSCLC admitted between January 2013 and January 2017. Patients were divided into the segmentectomy and lobectomy groups (40/group), according to the surgery they underwent. Blood loss, operation time, removal of drainage tube time, inflammatory response after operation, postoperative complications, postoperative lung function, local recurrence, and survival were compared.Blood loss and removal of drainage tube time were not significantly different between the 2 groups (all P > .05). Operation time in the segmentectomy group was longer than in the lobectomy group (P < .001). The postoperative interleukin-6, procalcitonin, and C-reactive protein changes in the segmentectomy group were significantly lower than in the lobectomy group (all P < .001). The pulmonary function at 2 weeks was significantly reduced in the 2 groups (all P < .001), but it was better in the segmentectomy group than in the lobectomy group (all P < .05). The 1- and 3-year local recurrence disease-free, and overall survival rates were not significantly different between the 2 groups (P > .05). The multivariable analysis could not identify any factor associated with local recurrence or survival (all P > .05).Thoracoscopic pulmonary segmentectomy and lobectomy are both acceptable for the treatment of early peripheral NSCLC, but segmentectomy was associated with lower postoperative inflammation and better postoperative pulmonary function than lobectomy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Toracoscopía , Adulto , Anciano , Biomarcadores de Tumor/sangre , Pérdida de Sangre Quirúrgica , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Drenaje , Estudios de Factibilidad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Tempo Operativo , Complicaciones Posoperatorias , Pruebas de Función Respiratoria , Estudios Retrospectivos , Tasa de Supervivencia
3.
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
4.
Anticancer Res ; 40(2): 983-990, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32014943

RESUMEN

BACKGROUND/AIM: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death. Patients eligible for surgery have better overall survival rate than patients who are not eligible. We investigated the prognostic value of p16 in patients who underwent surgery for lung cancer, in association with other factors such as PD-L1 and Ki-67. MATERIALS AND METHODS: Expression of p16 was evaluated along with the presence of Ki-67 and PD-L1 in 256 NSCLC patients treated only surgically. RESULTS: Adenocarcinoma was the prevalent histotype (56%) followed by squamous cell (29%) and differentiation grade of 3 was the most common (60%). p16 was detected in 83 patients (30%): low positivity (<10% cells) was observed in 30 samples (11%) and high positivity (>10 % cells) in 53 patients (20%). Ki-67 was detected in 89 patients (34%) with mild positivity in 46 patients (10-25% cells), moderate positivity (26-75% cells) in 30 patients (11%), and high positivity (>75% cells) in 13 patients (5%). An influence of p16 expression (p<0.05) along with grading and staging on overall survival (OS) was found. The average OS was 36 months, but the OS increased up to 54 months when patients were stratified according to p16 expression levels. The stratification by staging showed a significant prognostic value for p16 at an early stage (p<0.014). CONCLUSION: p16 significantly influences prognosis, notably at an early stage, along with other variables such as grading and staging.


Asunto(s)
Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales
5.
Medicine (Baltimore) ; 99(4): e18543, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31977847

RESUMEN

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer with a high mortality disease which has been positioned the first and second cancer morbidity of men and women in China, separately. Our study was to assess the prognostic meaningful of ubiquitin conjugating enzyme E2 T (UBE2T) expression in LUAD dependent on data acquired from The Cancer Genome Atlas (TCGA) and so as to increase further knowledge into the biological pathways involved in LUAD pathogenesis related to UBE2T.Information on gene expression and comparing clinical data were recognized and downloaded from TCGA. Gene set enrichment analysis (GSEA) created an arranged list of all genes s indicated by their connection with UBE2T expression.Our study cohort included 265 (54.5%) female and 221 (36.0%) male patients. The scatter plot and paired plot showed the difference of UBE2T expression between normal and tumor samples (P < .01). Overall survival (OS) analysis demonstrated that LUAD with UBE2T-high had a more terrible prognosis than that with UBE2T-low (P < .01). Multivariate analysis with the cox proportional hazards model indicated that the expression of UBE2T (hazard ratio [HR]: 1.28; 95% Confidence Interval (CI): 1.06-1.56; P = .011) and stage (HR: 2.02; 95% CI: 1.27-3.21; P = .003) were independent prognostic factors for patients with LUAD. The GSEA results showed that cell cycle, DNA replication, RNA degradation, oxidative phosphorylation, pathogenic Escherichia coli infection, citrate cycle tricarboxylic acid cycle, Alzheimer's disease, P53 signaling pathway, and purine metabolism are differentially enriched in UBE2T high expression phenotype.Our study found that the expression of UBE2T was significantly increased in LUAD patients and associated with several clinical features. UBE2T may be a potentially useful prognostic molecular biomarker of bad survival in LUAD, while further experimental ought to be performed to demonstrate the biologic effect of UBE2T.


Asunto(s)
Adenocarcinoma del Pulmón/patología , Neoplasias Pulmonares/patología , ARN Mensajero/biosíntesis , Enzimas Ubiquitina-Conjugadoras/biosíntesis , Adenocarcinoma del Pulmón/mortalidad , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Ciclo Celular , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fenotipo , Pronóstico , Factores de Riesgo , Factores Sexuales , Análisis de Supervivencia
6.
N Engl J Med ; 382(6): 503-513, 2020 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-31995683

RESUMEN

BACKGROUND: There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers. METHODS: A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until December 31, 2015, was completed for all participants. RESULTS: Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan (initially indeterminate). The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 person-years in the screening group and 4.91 cases per 1000 person-years in the control group; lung-cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; P = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9. CONCLUSIONS: In this trial involving high-risk persons, lung-cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening. There were low rates of follow-up procedures for results suggestive of lung cancer. (Funded by the Netherlands Organization of Health Research and Development and others; NELSON Netherlands Trial Register number, NL580.).


Asunto(s)
Tomografía Computarizada de Haz Cónico , Detección Precóz del Cáncer/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/mortalidad , Anciano , Bélgica/epidemiología , Reacciones Falso Positivas , Femenino , Humanos , Incidencia , Neoplasias Pulmonares/epidemiología , Masculino , Uso Excesivo de los Servicios de Salud , Persona de Mediana Edad , Países Bajos/epidemiología , Sistema de Registros , Factores Sexuales , Fumar/epidemiología
7.
Bull Cancer ; 107(1): 21-29, 2020 Jan.
Artículo en Francés | MEDLINE | ID: mdl-31980144

RESUMEN

The HIV infection remains a serious public health concern in France and around the world. Cancers are frequent among people living with HIV (PLWH) and have become the leading cause of mortality among this population in France. Certain non-AIDS-defining cancers are much more common among PLWH, such as anal carcinoma, Hodgkin lymphoma, hepatocellular carcinoma and lung cancer. The incidence of cancer among PLWH depending on various factors, virological control under combined antiretrovial therapies (cART), exposure prevention to oncogenic virus and toxics are of utmost importance, such as the implementation of specific screening programmes. Drug interactions between cART and oncologic treatments can lead to serious adverse effects or to a reduction in the therapeutic effects, therefore they require a close monitoring. The PLWH have been excluded from the oncologic clinical trials assessing the efficacy and toxicity profile of the immune checkpoints inhibitors (ICPi) because of an increased theoretical risk of inducing adverse events and a feared lack of efficacy in the immunocompromised population. However, the mostly retrospective clinical data reporting the use of ICPi among PLWH are somewhat reassuring with a safety and efficacy profile similar to what observed in HIV-negative patients. Regarding the "shock and kill" anti-HIV effects of ICPi, the preliminary clinical data available are still modest and relatively disappointing despite encouraging results obtained in vitro. HIV-associated cancers represent a particular care challenge due to the multiple comorbidities in the population and the high risk of drug interactions, thus the CANCERVIH national network is of particular interest within this context.


Asunto(s)
Infecciones por VIH/complicaciones , Sobrevivientes de VIH a Largo Plazo , Neoplasias/diagnóstico , Fármacos Anti-VIH/farmacología , Antineoplásicos/farmacología , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/tratamiento farmacológico , Interacciones de Drogas , Francia , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Inmunoterapia Adoptiva/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Neoplasias/inmunología
8.
BJOG ; 127(3): 389-395, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31794098

RESUMEN

OBJECTIVE: Presence of lung metastases in low-risk gestational trophoblastic neoplasia (GTN) is generally considered not to influence prognosis. However, in a recent study in the Netherlands, GTN patients with lung metastases had a higher recurrence rate and more disease-specific deaths compared with patients without metastases. The aim of the present study was to validate these findings in a different country. DESIGN: Historical cohort study. SETTING: Charing Cross Hospital, United Kingdom. POPULATION: A total of 1040 low-risk GTN patients treated with methotrexate (MTX) between 2002 and 2016 were identified: 65 with lung metastases (group 1) and 975 without metastases (group 2). METHODS: Baseline characteristics, MTX resistance, survival and recurrence rates were recorded and compared between both groups. MAIN OUTCOME MEASURES: MTX resistance, recurrence rate and survival. RESULTS: The occurrence of MTX resistance and median number of MTX courses to achieve remission was significantly higher in patients with lung metastases than patients without metastases (60% versus 38.9%, P = 0.001; and nine versus six courses, P < 0.001). All choriocarcinoma patients (n = 4) with lung metastases developed MTX resistance. The recurrence rate was also higher in group I (9.2% versus 2.7%; P = 0.012). Disease-specific survival was 100% in both groups. CONCLUSIONS: The presence of lung metastases at the start of MTX therapy is associated with increased incidence of MTX resistance and recurrence in low-risk GTN without affecting overall survival, which remains 100%. However, individuals with low-risk choriocarcinoma with lung metastases are likely to become resistant to MTX and primary multi-agent chemotherapy should be considered. TWEETABLE ABSTRACT: The presence of lung metastases appears to increase the risk of recurrence in low-risk GTN, but does not affect overall cure rates and survival.


Asunto(s)
Coriocarcinoma , Resistencia a Antineoplásicos/efectos de los fármacos , Enfermedad Trofoblástica Gestacional , Neoplasias Pulmonares , Metotrexato , Adulto , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Coriocarcinoma/tratamiento farmacológico , Coriocarcinoma/patología , Estudios de Cohortes , Femenino , Enfermedad Trofoblástica Gestacional/tratamiento farmacológico , Enfermedad Trofoblástica Gestacional/patología , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Estadificación de Neoplasias , Países Bajos/epidemiología , Embarazo , Recurrencia , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Reino Unido/epidemiología
9.
J Cancer Res Clin Oncol ; 146(1): 43-52, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31705294

RESUMEN

BACKGROUND: There are several studies comparing the difference between adenocarcinoma (AC) and squamous cell carcinoma (SqCC) of lung cancer. However, seldom studies compare the different overall survival (OS) between AC and SqCC at same clinical or pathological stage. The aim of the study was to investigate the 5-year OS between AC and SqCC groups. METHODS: Data were obtained from the Taiwan Society of Cancer Registry. There were 48,296 non-small cell lung cancer (NSCLC) patients analyzed between 2009 and 2014 in this retrospective study. We analyzed both the AC and SqCC groups by age, gender, smoking status, Charlson co-morbidity index (CCI) score, clinical TNM stage, pathological stage, tumor location, histologic grade, pleura invasion, performance status, treatment, stage-specific 5-year OS rate in each clinical stage I-IV and causes of death. We used propensity score matching to reduce the bias. RESULTS: The AC and SqCC groups are significantly different in age, gender, smoking status, CCI score, clinical TNM stage, pathological stage, tumor location, histologic grade, pleura invasion, performance status, treatment, stage-specific 5-year OS rate in each clinical stage and causes of death (p < 0.0001). The stage-specific 5-year OS rates between AC and SqCC were 79% vs. 47% in stage I; 50% vs. 32% in stage II; 27% vs. 13% in stage III; 6% vs. 2% in stage IV, respectively (all p values < 0.0001). CONCLUSIONS: AC and SqCC have significantly different outcomes in lung cancer. We suggest that these two different cancers should be analyzed separately to provide more precise outcomes in the future.


Asunto(s)
Adenocarcinoma del Pulmón/patología , Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/patología , Adenocarcinoma del Pulmón/mortalidad , Adenocarcinoma del Pulmón/terapia , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Masculino , Sistema de Registros , Estudios Retrospectivos , Taiwán/epidemiología
10.
J Cancer Res Clin Oncol ; 146(1): 67-74, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31786738

RESUMEN

PURPOSE: Marital status has been demonstrated as an independent prognostic factor in many cancer types. The impact of marital status on non-small cell lung cancer (NSCLC) survival has not been assessed at the population level. Here, we used the surveillance, epidemiology and end results (SEER) database, a US national cancer registry, to address this issue. METHODS: All patients diagnosed with NSCLC from 2004 to 2009 were identified in the SEER database (version 8.3.2, updated at April 14, 2016). Those with incomplete clinicopathological information were excluded. The tumor, node, metastasis (TNM) staging was based on the criteria of the American Joint Committee on Cancer (AJCC) 6th edition. We used propensity-score matching analysis to balance baseline characteristics between the patients who were married and those who were not married. The impact of marital status on cancer-specific survival was analyzed with Cox proportional-hazards regression. RESULT: A total of 72, 984 NSCLC patients (41, 095 married patients, 56.3%) were enrolled in this study. After propensity-score matching, 25, 617 patients in the married group were 1:1 matched with patients in the unmarried group. Being unmarried was found to be associated with significantly decreased cancer-specific survival (hazard ratio (HR): 1.142, 95% CI: 1.119-1.166, p < 0.001). Among the unmarried group, patients who were single had worse cancer-specific survival (median survival 12 months, 95% CI: 11.37-12.63 months) than those who were divorced (median survival 15 months, 95% CI: 14.24-15.76 months, p < 0.001) or widowed (median survival 15 months, 95% CI: 14.25-15.76 months, p < 0.001). CONCLUSION: This study shows that marital status is an independent prognostic factor for cancer-specific survival in NSCLC patients. Patients who were married had better cancer-specific survival compared to the unmarried ones.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/mortalidad , Estado Civil/estadística & datos numéricos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Femenino , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Sistema de Registros , Programa de VERF , Estados Unidos/epidemiología
11.
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
12.
Int J Radiat Oncol Biol Phys ; 106(1): 82-89, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31580927

RESUMEN

PURPOSE: To investigate the efficacy and safety of proton beam therapy (PBT) for the treatment of stage I non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Six hundred sixty-nine patients with 682 tumors histologically or clinically diagnosed stage I NSCLC according to the seventh edition of Union for International Cancer Control who received passive-scattering PBT from April 2004 and December 2013 in Japan were retrospectively reviewed to analyze survival, local control, and toxicities. RESULTS: Of 669 patients, 486 (72.6%) were men, with a median age of 76 years (range, 42-94 years). NSCLC was histologically confirmed in 440 patients (65.7%). Clinical T stages included T1a (n = 265; 38.9%), T1b (n = 216; 31.7%), and T2a (n = 201; 29.4%). The total irradiation doses of PBT ranged from 74.4 to 131.3 biological effective dose GyE (median, 109.6 biological effective dose GyE). The median follow-up period was 38.2 months (range, 0.6-154.5 months) for all patients. The 3-year overall survival and progression-free survival rates for all patients were 79.5% and 64.1%, respectively. For patients with stage IA tumors, the 3-year overall survival and progression-free survival rates were 82.8% and 70.6%, respectively, and the corresponding rates for patients with stage IB tumors were 70.8% and 47.3%, respectively. The 3-year local progression-free rates for all, stage IA, and stage IB patients were 89.8%, 93.5%, and 79.4%, respectively. The incidence of grade 2, 3, 4, and 5 pneumonitis was 9.8%, 1.0%, 0%, and 0.7%, respectively. The incidence of grade ≥3 dermatitis was 0.4%. No grade 4 or severe adverse events, other than pneumonitis, were observed. CONCLUSIONS: PBT appears to yield acceptable survival rates, with a low rate of toxicities.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Terapia de Protones/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Japón , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Supervivencia sin Progresión , Terapia de Protones/efectos adversos , Neumonitis por Radiación/epidemiología , Neumonitis por Radiación/patología , Radiodermatitis/epidemiología , Dosificación Radioterapéutica , Efectividad Biológica Relativa , Estudios Retrospectivos , Tasa de Supervivencia
13.
Int J Radiat Oncol Biol Phys ; 106(1): 90-99, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31586665

RESUMEN

PURPOSE: Our purpose was to develop predictive nomograms for overall survival (OS), progression-free survival (PFS), and time-to-progression (TTP) at 5 years in patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS: The study cohort included 714 ES-NSCLC patients treated with SABR from 2004-2015 with median follow-up of 59 months, divided into training and testing sets (8:2), with the former used for nomogram development. The least absolute shrinkage and selection operator were initially employed to screen for predictors of OS, PFS, and TTP, and identified predictors were subsequently applied toward Cox proportional hazards regression modeling. Significant predictors (P < .05) on multivariable regression were then used to develop nomograms, which were validated via evaluation of concordance indexes (C-index) and calibration plots. Finally, Kaplan-Meier method and Gray's test were employed to compare and confirm differences in outcomes among various groups and explore prognostic factors associated with local versus distant disease progression. RESULTS: Significant predictors of both OS and PFS at 5 years included age, sex, Charlson comorbidity index, diffusing capacity of carbon monoxide, systemic immune-inflammation index, and tumor size (P ≤ .01 for all). Eastern Cooperative Oncology Group performance status predicted for OS as well (P = .01), and both tumor size (P < .01) and minimum biological equivalent dose to 95% of planning target volume (PTV D95 BED10; P < .01) were predictive of TTP. The C-indexes for the OS, PFS, and TTP nomograms were 0.73, 0.68, and 0.60 in the training data set and 0.72, 0.66, and 0.59 in the testing data set, respectively. Tumor size > 2.45 cm and PTV D95 BED10 < 113 Gy were significantly associated with both local and distant progression. CONCLUSIONS: These prognostic nomograms can accurately predict for OS, PFS, and TTP at 5 years after SABR for ES-NSCLC and may thus help identify high-risk patients who could benefit from additional systemic therapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Nomogramas , Radiocirugia/métodos , Factores de Edad , Anciano , Anciano de 80 o más Años , Dióxido de Carbono/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Comorbilidad , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Modelos de Riesgos Proporcionales , Capacidad de Difusión Pulmonar , Curva ROC , Análisis de Regresión , Factores Sexuales , Resultado del Tratamiento
14.
Int J Cancer ; 146(2): 388-399, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31241180

RESUMEN

Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Fibrosis Pulmonar Idiopática/genética , Neoplasias Pulmonares/genética , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Metilación de ADN , Epigénesis Genética , Femenino , Humanos , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/patología , Estimación de Kaplan-Meier , Pulmón/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico
15.
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
16.
Anticancer Res ; 39(11): 6241-6247, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31704853

RESUMEN

BACKGROUND/AIM: We performed multimodality therapy comprising preoperative chemotherapy, extrapleural pneumonectomy (EPP), and radiation therapy for patients with malignant pleural mesothelioma (MPM). Although multimodality therapy resulted in good prognosis, further improvement is required. Therefore, herein, we analysed the prognostic factors using surgical specimens and searched for suitable molecular targets to improve the prognosis after multidisciplinary treatment. PATIENTS AND METHODS: Forty-six patients with MPM underwent multimodality therapy. Paraffin-embedded surgical samples were used for immunohistochemistry to evaluate the expression of phosphorylated (p-) AKT, extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and S6 ribosomal protein (S6RP). RESULTS: On univariate and multivariate analyses, significant differences were observed according to the histological type, pathological stage, and p-mTOR expression rate. CONCLUSION: The prognosis of MPM is affected by p-mTOR expression, suggesting that molecular-targeted treatment might be used during multimodal therapy for MPM.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Pulmonares/enzimología , Mesotelioma/enzimología , Proteína Quinasa 1 Activada por Mitógenos/análisis , Neoplasias Pleurales/enzimología , Serina-Treonina Quinasas TOR/análisis , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Cisplatino/administración & dosificación , Terapia Combinada/métodos , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/mortalidad , Mesotelioma/terapia , Persona de Mediana Edad , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Terapia Molecular Dirigida , Pemetrexed/administración & dosificación , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/terapia , Neumonectomía , Pronóstico , Proteínas Serina-Treonina Quinasas/análisis , Proteínas Serina-Treonina Quinasas/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
17.
Medicine (Baltimore) ; 98(44): e17773, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31689842

RESUMEN

OBJECTIVE: To evaluate the prognostic value of pancreatic neuroendocrine tumors (pNETs) with different metastatic patterns. METHODS: Data of pNETs cases were extracted from the Surveillance, Epidemiology, and End Result (SEER) database. They were classified according to the different metastatic patterns. We utilized chi-square test to compare the clinical and metastasis characteristics among different groups. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. Adjusted HRs with 95% CIs was calculated using Cox regression model to estimate prognostic factors. P < .05 was considered statistically significant. RESULTS: Among the 3909 patients, liver is the most metastatic organ, and isolated brain metastasis is the least common. At the same time, many patients have had multiple metastases. We studied the overall survival (OS) and cancer-specific survival (CCS) of the groups. OS: Non-organ metastasis: 5-year OS = 77.1%; Bone metastasis: median survival time (MST) = 56 m, 5-year OS = 42.7%; Liver metastasis: MST = 24 m, 5-year OS = 25.5%; Lung metastasis: MST = 14 m, 5-year OS = 33.7%; multiple metastases: MST = 7m, 5-year OS = 12.0%. CCS: Non-organ metastasis: 5-year OS = 84.2%; Bone metastasis: 5-year OS = 52.5%; Liver metastasis: MST = 27 m, 5-year OS = 28.6%; Lung metastasis: MST = 49 m, 5-year OS = 40.1%; multiple metastases: MST = 8 m, 5-year OS = 14.5%. In addition, the results showed that there were all statistical significances between the surgery and the no surgery group (all, P < .001). Multivariate analysis revealed that brain metastasis, multiple metastases, age over 60 years, unmarried, grade III/IV, regional/distant and no surgery were independently associated with decreased OS and CCS. CONCLUSIONS: pNETs patients without organ metastasis had the best survival outcomes, while multiple had the worst outcomes. There were no significant differences in bone metastasis, liver metastasis and lung metastasis. Surgery was still an option for patients with metastasis.


Asunto(s)
Neoplasias Óseas/mortalidad , Neoplasias Encefálicas/mortalidad , Neoplasias Hepáticas/mortalidad , Neoplasias Pulmonares/mortalidad , Tumores Neuroendocrinos/mortalidad , Neoplasias Pancreáticas/mortalidad , Anciano , Neoplasias Óseas/secundario , Neoplasias Encefálicas/secundario , Distribución de Chi-Cuadrado , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tumores Neuroendocrinos/secundario , Neoplasias Pancreáticas/patología , Pronóstico , Programa de VERF , Tasa de Supervivencia
18.
Semin Oncol ; 46(4-5): 380-384, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31735362

RESUMEN

BACKGROUND: Baseline tumor size (BTS) was recently indicated as prognostic of overall survival (OS) in patients advanced melanoma treated with pembrolizumab. We review the association between BTS and OS/progression-free survival (PFS) in patients with a diagnosis of advanced non-small-cell lung cancer (NSCLC) treated with atezolizumab. METHODS: Data from 1,461 patients with a diagnosis of advanced NSCLC enrolled in the OAK, POPLAR, BIRCH, and FIR trials and treated with atezolizumab were pooled and analyzed. Using Cox proportional hazards regression, we modeled the association between baseline SLD and survival outcomes. Multivariable analyses were adjusted for pretreatment ECOG PS, age, sex, race, smoking status, histology, count of prior treatments, PDL1 expression, serum LDH levels, and the presence of liver, lung, or brain lesions. RESULTS: On univariable and multivariable analysis, baseline sum of the longest diameters of target lesions (SLD) was identified as significantly associated with OS (hazard ratio [95% confidence interval] per decimeter: 1.64 [1.41-1.91], P < .001) and PFS (1.21 [1.07-1.38], P = .003). Median OS were 16 months versus 10 months for baseline SLD < median, versus baseline SLD ≥ median, respectively. Median PFS were 4 months versus 3 months, respectively. CONCLUSIONS: Large BTS was identified as an independent prognostic factor of worse OS and PFS, raising the need to evaluate atezolizumab as an earlier NSCLC treatment in future trials.


Asunto(s)
Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Inmunomodulación/efectos de los fármacos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Terapia Molecular Dirigida , Pronóstico , Resultado del Tratamiento , Carga Tumoral
20.
N Engl J Med ; 381(19): 1801-1808, 2019 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-31633894

RESUMEN

BACKGROUND: Neurodegenerative disorders have been reported in elite athletes who participated in contact sports. The incidence of neurodegenerative disease among former professional soccer players has not been well characterized. METHODS: We conducted a retrospective cohort study to compare mortality from neurodegenerative disease among 7676 former professional soccer players (identified from databases of Scottish players) with that among 23,028 controls from the general population who were matched to the players on the basis of sex, age, and degree of social deprivation. Causes of death were determined from death certificates. Data on medications dispensed for the treatment of dementia in the two cohorts were also compared. Prescription information was obtained from the national Prescribing Information System. RESULTS: Over a median of 18 years, 1180 former soccer players (15.4%) and 3807 controls (16.5%) died. All-cause mortality was lower among former players than among controls up to the age of 70 years and was higher thereafter. Mortality from ischemic heart disease was lower among former players than among controls (hazard ratio, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P = 0.02), as was mortality from lung cancer (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.001). Mortality with neurodegenerative disease listed as the primary cause was 1.7% among former soccer players and 0.5% among controls (subhazard ratio [the hazard ratio adjusted for competing risks of death from ischemic heart disease and death from any cancer], 3.45; 95% CI, 2.11 to 5.62; P<0.001). Among former players, mortality with neurodegenerative disease listed as the primary or a contributory cause on the death certificate varied according to disease subtype and was highest among those with Alzheimer's disease (hazard ratio [former players vs. controls], 5.07; 95% CI, 2.92 to 8.82; P<0.001) and lowest among those with Parkinson's disease (hazard ratio, 2.15; 95% CI, 1.17 to 3.96; P = 0.01). Dementia-related medications were prescribed more frequently to former players than to controls (odds ratio, 4.90; 95% CI, 3.81 to 6.31; P<0.001). Mortality with neurodegenerative disease listed as the primary or a contributory cause did not differ significantly between goalkeepers and outfield players (hazard ratio, 0.73; 95% CI, 0.43 to 1.24; P = 0.24), but dementia-related medications were prescribed less frequently to goalkeepers (odds ratio, 0.41; 95% CI, 0.19 to 0.89; P = 0.02). CONCLUSIONS: In this retrospective epidemiologic analysis, mortality from neurodegenerative disease was higher and mortality from other common diseases lower among former Scottish professional soccer players than among matched controls. Dementia-related medications were prescribed more frequently to former players than to controls. These observations need to be confirmed in prospective matched-cohort studies. (Funded by the Football Association and Professional Footballers' Association.).


Asunto(s)
Atletas , Enfermedades Neurodegenerativas/mortalidad , Fútbol , Adulto , Anciano , Anciano de 80 o más Años , Lesiones Encefálicas , Estudios de Casos y Controles , Causas de Muerte , Femenino , Cardiopatías/mortalidad , Humanos , Incidencia , Modelos Logísticos , Longevidad , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Nootrópicos/uso terapéutico , Estudios Retrospectivos , Escocia/epidemiología
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