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1.
Anticancer Res ; 40(2): 957-964, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014940

RESUMO

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.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/etiologia , Rearranjo Gênico , Neoplasias Pulmonares/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , Gerenciamento Clínico , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas de Fusão Oncogênica/genética , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral
2.
Anticancer Res ; 40(2): 983-990, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014943

RESUMO

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.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais
3.
Anticancer Res ; 40(2): 1007-1014, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014946

RESUMO

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.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Adulto , Idoso , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC
4.
Medicine (Baltimore) ; 99(5): e18959, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000421

RESUMO

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.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Toracoscopia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Perda Sanguínea Cirúrgica , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Drenagem , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Duração da Cirurgia , Complicações Pós-Operatórias , Testes de Função Respiratória , Estudos Retrospectivos , Taxa de Sobrevida
5.
J Cancer Res Clin Oncol ; 146(1): 67-74, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31786738

RESUMO

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.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Estado Civil/estatística & dados numéricos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Sistema de Registros , Programa de SEER , Estados Unidos/epidemiologia
6.
Oncology ; 98(1): 23-28, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31494653

RESUMO

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.


Assuntos
Substituição de Aminoácidos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mutação , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Receptores ErbB/genética , Feminino , Humanos , Biópsia Líquida , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
7.
Int J Cancer ; 146(2): 388-399, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31241180

RESUMO

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.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Fibrose Pulmonar Idiopática/genética , Neoplasias Pulmonares/genética , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Metilação de DNA , Epigênese Genética , Feminino , Humanos , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/patologia , Estimativa de Kaplan-Meier , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
8.
Int J Radiat Oncol Biol Phys ; 106(1): 82-89, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31580927

RESUMO

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.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Terapia com Prótons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Incidência , Japão , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Terapia com Prótons/efeitos adversos , Pneumonite por Radiação/epidemiologia , Pneumonite por Radiação/patologia , Radiodermatite/epidemiologia , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Estudos Retrospectivos , Taxa de Sobrevida
9.
Int J Radiat Oncol Biol Phys ; 106(1): 90-99, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586665

RESUMO

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.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Nomogramas , Radiocirurgia/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Dióxido de Carbono/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Comorbidade , Progressão da Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Modelos de Riscos Proporcionais , Capacidade de Difusão Pulmonar , Curva ROC , Análise de Regressão , Fatores Sexuais , Resultado do Tratamento
10.
Zhonghua Zhong Liu Za Zhi ; 41(12): 881-890, 2019 Dec 23.
Artigo em Chinês | MEDLINE | ID: mdl-31874543

RESUMO

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.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , China/epidemiologia , Consenso , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Sociedades Médicas , Taxa de Sobrevida
11.
Semin Oncol ; 46(4-5): 327-333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708233

RESUMO

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.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Saúde dos Veteranos/estatística & dados numéricos , Veteranos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Seguimentos , Humanos , Masculino , Oncologia , Pessoa de Meia-Idade , Mortalidade , Medicina de Precisão , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Fatores de Risco , Estados Unidos/epidemiologia
12.
Zhonghua Zhong Liu Za Zhi ; 41(10): 775-781, 2019 Oct 23.
Artigo em Chinês | MEDLINE | ID: mdl-31648501

RESUMO

Objective: To evaluate the efficacy and safety of apatinib combined with chemotherapy in the first-line treatment of advanced non-small cell lung cancer (NSCLC) with negative driving genes. Methods: From January 2016 to March 2018, 62 advanced NSCLC patients with negative driving genes diagnosed at Xuzhou Cancer Hospital were randomly divided into study group (30 cases) and control group (32 cases), respectively. The patients in the study group were treated with standard first-line chemotherapy combined with apatinib, while those in control group were treated with chemotherapy alone. Results: The disease control rate (DCR) and objective remission rate (ORR) in the study group were 60.0% and 16.7%, respectively, higher than 46.9% and 9.3% in the control group, but without statistical difference (P>0.05). The median progression-free survival (PFS) of study group and control group were 6.4 months and 4.9 months, respectively (P=0.004), and the median overall survival (OS) were 11.3 months and 9.2 months, respectively (P=0.006). Multivariate survival analysis indicated that treatment regimen (P=0.001) was the independent prognostic factor of PFS, and PS score (P=0.002), clinical stage (P=0.02) and treatment regimen (P<0.001) were the independent prognostic factors of OS. After treatment, the incidence of hypertension and hand-foot syndrome in the study group were 46.7% and 53.3%, respectively, significantly higher than 3.3% and 0 in the control group, respectively (P<0.05). The incidence of grade 3-4 adverse drug reactions (ADRs) in the study group was 26.7% (8/30), mainly including hypertension, hand-foot syndrome and bone marrow suppression. The incidence of grade 3-4 ADRs in the control group was 15.6% (5/32), all of which were bone marrow suppression, without significant difference (P=0.286). There was no difference in serum levels of VEGF and CEA between the two groups before treatment. After treatment, the serum level of VEGF in the study group was (169.3±10.1) pg/ml, lower than (211.8±16.7) pg/ml of the control group (P<0.05). Conclusion: Apatinib combined with first-line chemotherapy for advanced NSCLC patients with negative driving genes is safe and beneficial for survival. This therapeutic strategy can significantly prolong the PFS and OS, and further improvement and application can be considered as a choice in the clinical treatment.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Inibidores de Proteínas Quinases/uso terapêutico , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , China/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Síndrome Mão-Pé/complicações , Síndrome Mão-Pé/epidemiologia , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Incidência , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento
13.
Medicine (Baltimore) ; 98(43): e17559, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651857

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths among males and the second leading cause among females worldwide. Numerous studies have linked estrogen status to lung cancer outcome. However, there are studies with conflicting results about the effect of ERß on survival of lung cancer. The aim of this meta-analysis is to evaluate the prognostic impact of estrogen receptor beta expression on survival among NSCLC patients. METHODS: We will search 15 electronic databases, including PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI from inception to June 1, 2019. We will include all cohort studies comparing overall survival of NSCLC patients with high or low estrogen receptor beta expression. The database searches will be supplemented by searching through citations and references. Two reviewers will independently screen search results to identify eligible articles, complete data collection, and conduct quality assessment. All disagreements will be resolved by an independent third reviewer. Methodological quality of the included studies will be assessed using the Newcastle- Ottawa scale. Discrepancies will be resolved by consensus or by consulting a third author. Meta-analyses will be performed, and findings will be reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. RESULTS: The results will be submitted to a peer-reviewed journal for publication. CONCLUSION: This review will provide a comprehensive evaluation of the evidence on the prognostic impact of ERß expression among NSCLC patients and will help clinicians find potential treatments based on estrogen signaling.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Receptor beta de Estrogênio/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Projetos de Pesquisa , Análise de Sobrevida , Revisão Sistemática como Assunto
14.
Cancer Sci ; 110(12): 3663-3676, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31597217

RESUMO

Increasing evidence indicates that human forkhead box C1 (FOXC1) plays important roles in tumor development and metastasis. However, the underlying molecular mechanism of FOXC1 in non-small cell lung cancer (NSCLC) metastasis remains unclear. Here, we identified FOXC1 as an independent prognostic factor in NSCLC and showed clear biological implications in invasion and metastasis. FOXC1 overexpression enhanced the proliferation, migration and invasion of NSCLC cells, whereas FOXC1 silencing impaired the effects both in vitro and in vivo. Importantly, we found a positive correlation between FOXC1 expression and lysyl oxidase (LOX) expression in NSCLC cells and patient samples. Downregulation of LOX or LOX activity inhibition in NSCLC cells inhibited the FOXC1-driven effects on cellular migration and invasion. Xenograft models showed that inhibition of LOX activity by ß-aminopropionitrile monofumarate decreased the number of lung metastases. Mechanistically, we demonstrated a novel FOXC1-LOX mechanism that was involved in the invasion and metastasis of NSCLC. Dual-luciferase assay and ChIP identified that FOXC1 bound directly in the LOX promoter region and activated its transcription. Collectively, the present study offered new insight into FOXC1 in the mediation of NSCLC metastasis through interaction with the LOX promoter and further revealed that targeted inhibition of LOX protein activity could prevent lung metastasis in murine xenograft models. These data implicated FOXC1 as a potential therapeutic strategy for the treatment of NSCLC metastasis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Fatores de Transcrição Forkhead/fisiologia , Neoplasias Pulmonares/patologia , Regiões Promotoras Genéticas , Proteína-Lisina 6-Oxidase/genética , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Proteína-Lisina 6-Oxidase/fisiologia
15.
J Surg Oncol ; 120(8): 1486-1496, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31602661

RESUMO

BACKGROUND AND OBJECTIVES: To investigate non-lung cancer specific mortality between stage IA non-small cell lung cancer (NSCLC) tumors less than and equal to 2 cm treated with lobectomy and sublobectomy. METHODS: Surveillance, epidemiology, and end results database was queried for patients who underwent lobectomy and sublobectomy. Propensity score matching (PSM) was used to achieve balance in clinicopathological characteristics. We used Fine-and-Gray hazard functions to analyze cause-specific mortality and risk factors. Standardized mortality ratios were calculated to describe cause specific mortality relative to the general population. RESULTS: After PSM, 3,844 patients underwent lobectomy and 1,922 patients underwent sublobectomy. Three leading causes of non-lung cancer mortality were cardiovascular disease (CVD), chronic obstructive pulmonary diseases (COPD), and other cancers. The 5-year cumulative non-lung cancer mortality of lobectomy and sublobectomy groups were 11.4% and 14.0%, respectively (P = .090). Multivariate analyses revealed that age, sex, histology, tumor size, and marital status (P < .01) were independent predictors of non-lung cancer specific mortality. In both groups, risks of CVD specific mortality were comparable to that in the general population, whereas the risk of COPD specific mortality was higher relative to the general population. CONCLUSIONS: As a significant competing event, non-lung cancer specific mortality is comparable between stage IA NSCLC tumors less than equal to 2 cm treated with lobectomy and sublobectomy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Doenças Cardiovasculares/mortalidade , Causas de Morte , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Adulto , Fatores Etários , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Estado Civil , Análise por Pareamento , Pessoa de Meia-Idade , Análise Multivariada , Pontuação de Propensão , Programa de SEER , Fatores Sexuais , Estados Unidos/epidemiologia , Adulto Jovem
16.
Cancer Sci ; 110(12): 3738-3745, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31608537

RESUMO

The prognosis of non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) is poor, and 5%-20% of those receiving chemotherapy experience ILD exacerbation. To evaluate the safety and efficacy of nab-paclitaxel plus carboplatin for NSCLC patients with ILD, we undertook a multicenter phase II study. Chemotherapy-naïve patients with advanced NSCLC and mild or moderate ILD received nab-paclitaxel (100 mg/m2 , days 1, 8, and 15) plus carboplatin (area under the curve = 6, day 1) every 3 weeks for 4 cycles (maximum, 6 cycles). Interstitial lung diseases were diagnosed based on criteria for fibrosing interstitial pneumonia. The primary endpoint was the prevalence of exacerbation-free ILD 28 days after completion of protocol treatment. Secondary endpoints were response rate, progression-free survival, overall survival, prevalence of exacerbation-free ILD, and toxicity. Ninety-four patients were enrolled, and 92 patients received any protocol treatment. Median age was 70 years, and 58% had nonsquamous histology. In the primary analysis, the prevalence of exacerbation-free ILD 28 days after protocol treatment was 95.7% (88/92; 90% confidence interval, 90.3-98.5), which met the primary endpoint. Response rate was 51% (95% confidence interval, 40%-62%). At the time of data cut-off, median progression-free survival was 6.2 months, and median overall survival was 15.4 months. The most common grade 3/4 adverse events were neutropenia (75%), leukopenia (53%), anemia (48%), and thrombocytopenia (20%). Two treatment-related deaths (1 each of pulmonary infection and ILD exacerbation) were observed. This study showed that a combination of nab-paclitaxel with carboplatin was tolerable in NSCLC patients with mild or moderate ILD in terms of safety. This study is registered at the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN 000012989).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Doenças Pulmonares Intersticiais/complicações , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Doenças Pulmonares Intersticiais/epidemiologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Estudos Prospectivos
18.
Anticancer Res ; 39(10): 5725-5731, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570474

RESUMO

BACKGROUND/AIM: In lung cancer (LC) patients, pre-existing interstitial lung disease (ILD) is a risk of chemotherapy-associated acute exacerbation of ILD (AE-ILD). AE-ILD shows a diverse clinical course varying from fatal respiratory failure to asymptomatic event, and the prognostic impact is still unclear. MATERIALS AND METHODS: We retrospectively evaluated the association between the prognosis and AE-ILD in 86 LC patients with pre-existing ILD who were treated with cytotoxic chemotherapy, especially focusing on histological types of LC. RESULTS: Thirty (34.9%) patients had AE-ILD, that was significantly associated with a poor prognosis in LC patients with ILD. When analyzed by histological types, a significant association of AE-ILD with shorter survival was observed only in the small cell LC (SCLC) group, but not in the non-small cell LC group. CONCLUSION: The development of AE-ILD by cytotoxic chemotherapy is associated with poor prognosis in LC patients with ILD, especially in patients with SCLC.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Doenças Pulmonares Intersticiais/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia
19.
Anticancer Res ; 39(9): 4987-4993, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519605

RESUMO

BACKGROUND/AIM: For immune checkpoint inhibitor (ICI)-pretreated patients, docetaxel and ramucirumab (DOC+RAM) combination therapy may be more effective compared to patients not receiving ICI treatment. PATIENTS AND METHODS: From June 2013 to July 2018, 39 patients with advanced/recurrent non-small cell lung cancer underwent DOC+RAM therapy. We analyzed the efficacy and safety of DOC+RAM therapy based on the presence (pre-ICI+) or absence (pre-ICI-) of ICI pretreatment history. RESULTS: Of the 39 patients treated with DOC+RAM, we identified 18 (46%) pre-ICI+ patients. Overall response rates for DOC+RAM concerning pre-ICI+ and pre-ICI- patients were 38.9% vs. 19.0%, respectively. Median progression-free survival (PFS) was 5.7 vs. 2.3 months [hazard ratio(HR)=0.36; 95% confidence interval (CI)=0.16-0.80]. Adverse events such as fever, myalgia, arthritis, pleural effusion, and pneumonitis tended to be increased in pre-ICI+ patients. CONCLUSION: Despite increased toxicity concerns, DOC+RAM therapy in pre-ICI+ patients showed a trend for tumor regression improvement and statistically significant prolongation of PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Docetaxel/administração & dosagem , Sinergismo Farmacológico , Feminino , Humanos , Imunomodulação/efeitos dos fármacos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
20.
Anticancer Res ; 39(9): 5077-5081, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519618

RESUMO

BACKGROUND/AIM: Patient performance scores are used widely in clinical practice to assess a patient's general condition. The aim of this study was to evaluate the prognostic role of Eastern Cooperative Oncology Group performance score (ECOG PS) before, after and its changes during chemoradiotherapy in patients with stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Records of 99 patients with stage III NSCLC were evaluated. ECOG PS before, during and after chemoradiotherapy was analyzed for prognostic impact on overall (OS) and event-free (EFS) survival. RESULTS: Median OS considering the entire cohort was 20.8 months (range=15.3-26.2 months). Median OS, and 1- and 2-year survival rates were 26.4 months, 85% and 53% in patients with ECOG PS 0 versus 18.9 months, 69% and 37% in patients with ECOG PS 1 (p=0.1, log-rank test), respectively. After the first follow-up, 35% of patients presented worsening ECOG PS, while in 65% it was stable or improved. Median EFS according to ECOG PS 0, 1, 2 and 3 was 9.6, 9.0, 7.9 and 3.5 months, respectively, at the first follow-up (p=0.018, log-rank test). Deterioration of ECOG PS after chemoradiotherapy resulted in reduced OS in the subgroups with initial ECOG PS 0 and 1 (p=0.005 and p=0.001, log-rank test). CONCLUSION: ECOG PS and its changes have a strong impact on patient outcome. Deterioration of performance status was a strong negative prognostic factor for EFS and OS.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Quimiorradioterapia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Tomografia Computadorizada por Raios X
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