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1.
Cancer Treat Rev ; 85: 101995, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32113080

RESUMO

Up to one in four patients with nasopharyngeal carcinoma present with non-metastatic stage IV disease (i.e. T4 or N3). Distinct failure patterns exist, despite the routine adoption of contemporary treatment modalities such as intensity modulated radiotherapy and systemic chemotherapy. Concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy or induction chemotherapy followed by CCRT are commonly employed in this setting, with the latter emerging as the preferred option. Additionally, emerging radiation technologies like proton therapy has become available offering new opportunities for prevention of radiation-induced side effects. This article reviews not only the current treatment strategies, but also discusses novel ways to tackle this challenging disease with respect to the patterns of failure.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Causas de Morte , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Biópsia por Agulha , Quimiorradioterapia/métodos , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Quimioterapia de Indução/métodos , Masculino , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/mortalidade , Invasividade Neoplásica/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
2.
J Laryngol Otol ; 134(4): 338-343, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32172705

RESUMO

OBJECTIVES: The conclusive prognostic significance of cyclo-oxygenase-2 has been determined in various cancers but not in nasopharyngeal carcinoma. Therefore, this study aimed to evaluate the relationship of cyclo-oxygenase-2 expression with the survival outcome and treatment response of nasopharyngeal carcinoma patients via a systematic meta-analysis approach. METHODS: A meta-analysis was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses ('PRISMA') checklist. The primary clinical characteristics of patients, and hazard ratios with 95 per cent confidence intervals of overall survival data, were tabulated from eligible studies. The relationship of cyclo-oxygenase-2 expression with survival outcome (expressed as hazard ratio) and treatment response (expressed as odds ratio) in nasopharyngeal carcinoma patients was analysed, and explained with the aid of forest plot charts. RESULTS AND CONCLUSION: The pooled hazard ratio for overall survival was 2.02 (95 per cent confidence interval = 1.65-2.47). This indicates that the over-expression of cyclo-oxygenase-2 is significantly associated with the poor survival of nasopharyngeal carcinoma patients. The pooled odds ratio of 0.98 (95 per cent confidence interval = 0.27-3.49) reveals that over-expression of cyclo-oxygenase-2 was not significantly related to the treatment outcome.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Carcinoma Nasofaríngeo/enzimologia , Neoplasias Nasofaríngeas/patologia , Tratamento Farmacológico/métodos , Feminino , Humanos , Masculino , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/terapia , Prognóstico , Radioterapia/métodos , Análise de Sobrevida , Resultado do Tratamento
3.
Medicine (Baltimore) ; 99(2): e18545, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914029

RESUMO

This study aimed to determine the impact of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) on the prognosis of nasopharyngeal carcinoma (NPC) before and after intensity modulated radiotherapy (IMRT).Pre/post-treatment and changes in inflammatory biomarker levels of 207 patients who were diagnosed with NPC and received IMRT between January 2012 and December 2014 were analyzed, and the cellular biomarker analyses were from patient blood. ROC (receiver operating characteristic) analysis was used to decide the optimal cutoff values of NLR and changes in NLR (ΔNLR) and PLR (ΔPLR). The Kaplan-Meier and logarithmic rank methods were used to compare overall survival times between groups. Univariate analysis was used to investigate the effects of age, gender, histology, Karnofsky performance score (KPS), TNM stage, clinical stage, course of disease and lymphocyte, neutrophil and platelet counts as well as alkaline phosphatase (ALP) levels on the prognosis of NPC. The independent predictors of OS were determined by Cox multivariate regression analysis.The optimal cut-off values of NLR, PLR, ΔNLR and ΔPLR were 2.49, 155.82, 1.80, and 100.00, respectively. These were used to classify patients into high (NLR > 2.49) and low NLR groups (NLR < 2.49); high (PLR>155.82) and low (PLR < 155.82) PLR groups; high (ΔNLR>1.80) and low ΔNLR groups (ΔNLR < 1.80); high (ΔPLR > 100.00) and low ΔPLR groups (ΔPLR < 100.00). TNM stage, clinical stage and ALP levels were highly correlated with high NLR and PLR. Cox multivariate regression analysis suggested that the ΔNLR (HR = 2.89, 95% CI: 1.33∼2.78) was independent of the characteristics for NPC.As a novel inflammatory index, ΔNLR appears to have some predictive power for the prognosis of patients with NPC.


Assuntos
Linfócitos/efeitos da radiação , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Neutrófilos/efeitos da radiação , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Contagem de Células Sanguíneas , Plaquetas/patologia , Plaquetas/efeitos da radiação , Feminino , Humanos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias/métodos , Neutrófilos/patologia , Valor Preditivo dos Testes , Prognóstico , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos
4.
Oncology ; 98(3): 154-160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995803

RESUMO

INTRODUCTION: Nasopharyngeal cancer (NPC) is a common malignancy in Southeast Asia with a high mortality rate. Previous studies have shown that the patient survival rate is <80% worldwide. At the Dharmais Cancer Hospital, NPC is the first of the top 10 diseases with the highest rate of stage III cancer progression. OBJECTIVE: This study aims to determine the 5-year survival rate of patients with NPC based on tumor response and their prognostic factors after receiving neoadjuvant chemotherapy, followed by chemoradiation. METHODS: The records of 261 patients between January 2009 and December 2013 were retrospectively analyzed. All patients with NPC who received neoadjuvant chemotherapy, followed by chemoradiation, at the Dharmais Cancer Hospital from 2009 to 2013 were identified. Patients with metastasis were excluded. The primary endpoint of this study was overall survival, which was defined as the time from the date of treatment to the date of death. The survival curve was analyzed using the Kaplan-Meier method. The Cox proportional hazard model was used for the multivariate analysis of prognostic factors. RESULTS: The tumor response rates for patients with complete response (CR), partial response (PR), and progressive disease (PD) were 33.7, 45.2, and 21.2%, respectively. The 5-year overall survival rate was 38.6%. The 5-year survival rates based on tumor response among CR, PR, and PD patients were 71.0, 30.4, and 10.6%, respectively. The significant independent prognostic factors were tumor response, educational background, job, alcohol consumption, clinical stage, and prompt treatment. CONCLUSION: The survival probability of patients with NPC receiving neoadjuvant chemotherapy, followed by chemoradiation, was higher in the CR group than in the PR and PD groups. This confirms that early detection can improve the patient's survival. Long-term follow-up is required to determine the factors influencing tumor response in NPC.


Assuntos
Quimiorradioterapia Adjuvante , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Terapia Neoadjuvante , Adulto , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/mortalidade , Progressão da Doença , Feminino , Humanos , Indonésia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Indução de Remissão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
5.
Medicine (Baltimore) ; 99(4): e18974, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977914

RESUMO

We aimed to develop a nomogram based on a population-based cohort to estimate the individualized overall survival (OS) for patients with nasopharyngeal carcinoma (NPC) and compare its predictive value with that of the traditional staging system.Data for 3693 patients with NPC were extracted from the Surveillance, Epidemiology, and End Results dataset and randomly divided into two sets: training (n = 2585) and validation (n = 1108). On the basis of multivariate Cox regression analysis, a nomogram was constructed to predict the 3-, 5-, and 10-year survival probability for a patient. The performance of the nomogram was quantified with respect to discrimination, calibration, and clinical utility.In the training set, age, sex, race, marital status, histological type, T stage, N stage, M stage, radiotherapy, and chemotherapy were selected to develop a nomogram for predicting the OS probability based on the multivariate Cox regression model. The nomogram was generally more discriminative compared with the American Joint Committee on Cancer 7th staging system. Calibration plots exhibited an excellent consistency between the observed probability and the nomogram's prediction. Categorical net classification improvement and integrated discrimination improvement suggested that the predictive accuracy of the nomogram exceeded that of the classic staging system. With respect to decision curve analyses, the nomogram exhibited preferable net benefit gains than the staging system across a wide range of threshold probabilities.This proposed nomogram exhibits an excellent performance with regard to its predictive accuracy, discrimination capability, and clinical utility, and thus can be used as a convenient and reliable tool for prognosis prediction in patients with NPC.


Assuntos
Carcinoma Nasofaríngeo/mortalidade , Nomogramas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Melhoria de Qualidade , Programa de SEER/estatística & dados numéricos , Adulto Jovem
6.
Ann Otol Rhinol Laryngol ; 129(3): 287-293, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31701754

RESUMO

AIM: Endoscopic endonasal nasopharyngectomy (EEN) for recurrent nasopharyngeal carcinoma (rNPC) is being increasingly used due to the added high magnification, reduced morbidities associated with open procedures and good survival outcomes. Most studies looked at usage of EEN in patients with lower recurrent staging (rT1 and rT2) although more and more surgeons are studying the outcome of EEN in advanced rNPC (rT3 and rT4). The aims of this study were to report the long-term 5-year survival outcome of EEN performed in patients with advanced rNPC, and to determine any prognostic factors for patients' survival. METHODS: All patients who underwent EEN for advanced rNPC between January 2003 and December 2015 inclusive were analyzed. All surgeries were performed in University Malaya Medical Centre in Kuala Lumpur and Queen Elizabeth Hospital in Sabah. We reported the 5-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) and any related complications and significant prognostic factors. RESULTS: Twelve patients with rNPC (2 rT3 and 10 rT4) were followed-up over a mean duration of 44.8 months (range, 40-440 weeks). The 5-year OS was 50.0% (mean 44.75 months), DFS was 25.0% (mean 35.25 months) and the DSS was 58.3% (mean 43.33 months). No severe operative complications were encountered and no independent prognostic factors for survival outcome were identified. CONCLUSION: This is the first report in English that exclusively described the long-term 5-year survival data in patients with both rT3 and rT4 recurrent NPC after EEN. The data suggest that EEN is a feasible treatment to improve survival with minimal morbidities in patients with rT3 and rT4 recurrent NPC. However, more studies with larger patient size is recommended.


Assuntos
Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/cirurgia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/cirurgia , Cirurgia Endoscópica por Orifício Natural , Recidiva Local de Neoplasia/cirurgia , Faringectomia/métodos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Reoperação , Terapia de Salvação
7.
Eur Radiol ; 30(1): 537-546, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31372781

RESUMO

OBJECTIVES: To establish and validate a radiomics nomogram for prediction of induction chemotherapy (IC) response and survival in nasopharyngeal carcinoma (NPC) patients. METHODS: One hundred twenty-three NPC patients (100 in training and 23 in validation cohort) with multi-MR images were enrolled. A radiomics nomogram was established by integrating the clinical data and radiomics signature generated by support vector machine. RESULTS: The radiomics signature consisting of 19 selected features from the joint T1-weighted (T1-WI), T2-weighted (T2-WI), and contrast-enhanced T1-weighted MRI images (T1-C) showed good prognostic performance in terms of evaluating IC response in two cohorts. The radiomics nomogram established by integrating the radiomics signature with clinical data outperformed clinical nomogram alone (C-index in validation cohort, 0.863 vs 0.549; p < 0.01). Decision curve analysis demonstrated the clinical utility of the radiomics nomogram. Survival analysis showed that IC responders had significant better PFS (progression-free survival) than non-responders (3-year PFS 84.81% vs 39.75%, p < 0.001). Low-risk groups defined by radiomics signature had significant better PFS than high-risk groups (3-year PFS 76.24% vs 48.04%, p < 0.05). CONCLUSIONS: Multiparametric MRI-based radiomics could be helpful for personalized risk stratification and treatment in NPC patients receiving IC. KEY POINTS: • MRI Radiomics can predict IC response and survival in non-endemic NPC. • Radiomics signature in combination with clinical data showed excellent predictive performance. • Radiomics signature could separate patients into two groups with different prognosis.


Assuntos
Quimioterapia de Indução/métodos , Imagem por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Nomogramas , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Máquina de Vetores de Suporte , Análise de Sobrevida , Resultado do Tratamento
8.
Medicine (Baltimore) ; 98(51): e18036, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860954

RESUMO

Cullin 4A (CUL4A) is a protein of E3 ubiquitin ligase with many cellular processes. CUL4A could regulate cell cycle, development, apoptosis, and genome instability. This study aimed to analyze the expression of CUL4A in nasopharyngeal carcinoma (NPC) tissues and the associations of CUL4A expression with prognostic significance. A total of 115 NPC patients were collected to assess the protein expression of CUL4A by immunohistochemistry, so as to analyze the relationships between CUL4A expression and clinicopathological and prognostic parameters. All patients were followed-up until death or 5 years. The results showed that high expression of CUL4A was significantly associated with larger primary tumor size (P = .026), higher nodal status (P = .013), more distant metastasis (P = .020), and higher TNM stage (P = .005). Kaplan-Meier curves showed that patients with higher CUL4A expression had significantly shorter overall survival (OS) and progression-free survival (PFS) (both P < .001). In multivariate Cox analysis, CUL4A is an independent prognostic factor for OS (P = .016; hazard ratio [HR] = 2.770, 95% CI: 1.208-6.351) and PFS (P = .022; HR = 2.311, 95% CI: 1.126-4.743). In conclusion, high expression of CUL4A was associated with advanced disease status of NPC, and might serve as an independent prognostic factor.


Assuntos
Proteínas Culina/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/mortalidade , Adulto , Idoso , China , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
9.
Medicine (Baltimore) ; 98(51): e18484, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861031

RESUMO

Although induction chemotherapy (IC) combined with intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy (CC) is the new standard treatment option in locoregionally advanced nasopharyngeal carcinoma (NPC), many patients fail to receive CC. The aim of this study was to investigate long-term survival outcomes and toxicities in these patients who are treated with IC before IMRT without CC.We retrospectively reviewed 332 untreated, newly diagnosed locoregionally advanced NPC patients who received IC before IMRT alone at our institution from May 2008 through April 2014. The IC was administered every 3 weeks for 1 to 4 cycles. Acute and late radiation-related toxicities were graded according to the acute and late radiation morbidity scoring criteria of the radiation therapy oncology group. The accumulated survival was calculated according to the Kaplan-Meier method. The log-rank test was used to compare the difference in survival.With a median follow-up duration of 65 months (range: 8-110 months), the 5-year estimated locoregional relapse-free survival, distant metastasis-free survival, progression-free survival (PFS), and overall survival rates were 93.4%, 91.7%, 85.8%, and 82.5%, respectively. Older age and advanced T stage were adverse prognostic factors for overall survival, and the absence of comorbidity was a favorable prognostic factor for PFS. However, acceptable acute complications were observed in these patients.IC combined with IMRT alone provides promising long-term survival outcomes with manageable toxicities. Therefore, the omission of CC from the standard treatment did not affect survival outcomes.


Assuntos
Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Radioterapia de Intensidade Modulada , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/radioterapia , Estudos Retrospectivos , Falha de Tratamento , Adulto Jovem
10.
Medicine (Baltimore) ; 98(42): e17486, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626102

RESUMO

BACKGROUND: It is unclear whether cetuximab (CTX) plus cisplatin-based concurrent chemoradiotherapy (CCRT) delivers equivalent or improved results over standard CCRT in locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS: The strategy involved searching the PubMed, Embase, Cochrane Library, and Web of Science. Pooled hazard ratios (HRs) for overall survival (OS), distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRFS), and disease-free survival (DFS), and pooled risk ratios for adverse events were meta-analyzed. RESULTS: In all, 1744 patients in 5 clinical trials were included in the analysis. Compared with CCRT group, CTX plus CCRT significantly improved DFS (HR = 0.59, 95% confidence interval [CI]: 0.41-0.86, P = .006) and distant metastasis failure-free survival (HR = 0.54, 95% CI: 0.38-0.76, P = .0004), rather than OS (HR = 0.70, 95% CI: 0.44-1.09, P = .12) and local-regional failure-free survival (HR = 0.82, 95% CI: 0.54-1.22, P = .33). CONCLUSIONS: CTX plus CCRT might achieve higher DFS and DMFS with no significant difference in OS and LRFS. CTX plus CCRT group was associated with more grade 3-4 skin rash, mucositis and dermatitis. Large randomized trials were urgent to fully explore the usefulness of this treatment in the locally advanced NPC patients.


Assuntos
Antineoplásicos/administração & dosagem , Cetuximab/administração & dosagem , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Humanos , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/mortalidade , Intervalo Livre de Progressão , Resultado do Tratamento
11.
Medicine (Baltimore) ; 98(38): e17176, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567957

RESUMO

BACKGROUND: The aim of this study was to investigate the use of pretreatment platelet-to-lymphocyte ratio (PLR) as a prognostic marker in patients with nasopharyngeal carcinoma (NPC). METHODS: A literature search was conducted using online databases such as MEDLINE, EMBASE, Cochrane Library, and WangFang. Overall survival (OS), progression-free survival (PFS), and clinicopathological features were generated and compared. RESULTS: Ten studies that included 3388 patients were analyzed in this meta-analysis. Among them, 8 studies with 3033 patients with NPC investigated the prognostic role of PLR for OS and showed that elevated PLR was associated with poor OS (HR: 1.77, 95% CI: 1.46-2.15, P < .001). Five studies that included 1156 patients investigated the role of PLR in predicting PFS, and showed that high PLR was associated with poor PFS (HR: 1.65, 95% CI: 1.26-2.17, P < .001). Moreover, high PLR correlated with the N stage (N2-3 vs N0-1; OR: 1.55, 95% CI: 1.02-2.34, P = .04). CONCLUSION: Our study suggested that high PLR is associated with worse prognosis in patients with NPC. Pretreatment PLR could serve as a simple, promising indicator for prognostic evaluation in patients with NPC.


Assuntos
Contagem de Linfócitos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Contagem de Plaquetas , Plaquetas , Humanos , Linfócitos , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/mortalidade , Análise de Sobrevida
12.
BMC Cancer ; 19(1): 908, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511059

RESUMO

BACKGROUND: This study aimed to evaluate the prognostic value of maximal standard uptake values (SUVmax) of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) comparing with Epstein-Barr virus (EBV) DNA levels in de novo metastatic nasopharyngeal carcinoma (NPC) patients. METHODS: From December 2006 to December 2016, 253 de novo metastatic NPC patients assessed by PET/ computed tomography were involved in current study. SUVmax-T, SUVmax-N, and SUVmax-M referred to the SUVmax at the primary tumor, cervical lymph nodes, and metastatic lesions respectively. Overall survival (OS) was the primary endpoint. RESULT: Patients who died during the follow-up had significantly higher SUVmax-N, SUVmax-M, and EBV DNA level than those in the patients who were alive. SUVmax-N and SUVmax-M were positively correlated with EBV DNA level. The cut-off values of SUVmax-T, SUVmax-N, SUVmax-M, and EBV DNA were 17.0, 12.7, and 6.9, and 13,800 copies/mL respectively, which were determined by receiver operating characteristic (ROC) curve analysis. Patients with elevated SUVmax-N, SUVmax-M, and EBV DNA levels had a lower 3-year OS rate. In multivariate analysis, the independent prognostic factors of OS included EBV DNA, metastatic site, and locoregional radiotherapy application, while SUVmax was not an independent prognostic factor. CONCLUSION: In de novo metastatic NPC patients, higher SUVmax-N and SUVmax-M were associated with worse prognosis. However, the predictive ability of SUVmax-N and SUVmax-M was poorer than that of EBV DNA.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Fluordesoxiglucose F18 , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/etiologia , Tomografia por Emissão de Pósitrons , Adulto , Idoso , DNA Viral , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/etiologia , Neoplasias Nasofaríngeas/mortalidade , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Curva ROC
13.
Technol Cancer Res Treat ; 18: 1533033819874807, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31522611

RESUMO

Due to the critical role of inflammation in nasopharyngeal carcinoma, we aim to investigate the correlation between nasopharyngeal carcinoma prognosis and the levels of tumor necrosis factor α and macrophages for the development of new prognostic models. The levels of tumor necrosis factor-α and CD68-positive macrophages were measured in 111 primary nasopharyngeal carcinoma specimens by immunohistochemistry. Kaplan-Meier analysis showed that, compared with nonelevated tumor necrosis factor-α levels, elevated tumor necrosis factor α levels were correlated with poorer 10-year distant metastasis-free survival (24.5% vs 5.2%, P = .004) and bone metastasis-free survival (17.0% vs 0.0%, P = .001). Multivariate analysis revealed that tumor necrosis factor α level was an independent prognostic factor for distant metastasis-free survival (hazard ratio = 16.765, P = .001), while the level of CD68-positive macrophages was a favorable independent prognostic factor for cancer-specific survival (hazard ratio = 0.481, P = .023) and disease-free survival (hazard ratio = 0.403, P = .010). Additionally, several prognostic models that considered tumor-node-metastasis stage alone or in combination with tumor necrosis factor α and/or CD68-positive macrophage levels were compared by receiver operating characteristic curve analysis. Interestingly, the T_score model, which considered the tumor necrosis factor α level alone, could better predict the distant metastasis-free survival and bone metastasis-free survival, whereas the MT model, which considered the combination of T stage and CD68-positive macrophage level, could better predict the cancer-specific survival and disease-free survival of patients with nasopharyngeal carcinoma. Elevated tumor necrosis factor-α levels and decreased CD68-positive macrophage levels in primary nasopharyngeal carcinoma tissues are unfavorable prognostic indicators in nasopharyngeal carcinoma. The T_score model or the MT model could be better prognostic models than those currently available for nasopharyngeal carcinoma and could be used to select high-risk patients and aid in the design of individualized immunotherapy.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Macrófagos/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/mortalidade , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Idoso , Biomarcadores , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Fator de Necrose Tumoral alfa/genética
14.
Cancer Treat Rev ; 79: 101890, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31470314

RESUMO

As a consequence of the current excellent loco-regional control rates attained using the generally accepted treatment paradigms involving intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC), only 10-20% of patients will suffer from local and/or nodal recurrence after primary treatment. Early detection of recurrence is important as localized recurrent disease is still potentially salvageable, but this treatment often incurs a high risk of major toxicities. Due to the possibility of radio-resistance of tumors which persist or recur despite adequate prior irradiation and the limited tolerance of adjacent normal tissues to sustain further additional treatment, the management of local failures remains one of the greatest challenges in this disease. Both surgical approaches for radical resection and specialized re-irradiation modalities have been explored. Unfortunately, available data are based on retrospective studies, and the majority of them are based on a small number of patients or relatively short follow-up. In this article, we will review the different salvage treatment options and associated prognostic factors for each of them. We will also propose a treatment algorithm based on the latest available evidence and discuss the future directions of treatment for locally recurrent NPC.


Assuntos
Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Terapia Combinada , Diagnóstico por Imagem/métodos , Gerenciamento Clínico , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/mortalidade , Estadiamento de Neoplasias , Prognóstico , Recidiva , Retratamento , Resultado do Tratamento
15.
PLoS Genet ; 15(8): e1008325, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31430288

RESUMO

The role of long non-coding RNA (lncRNA) in the progression of Nasopharyngeal carcinoma (NPC) has not been fully elucidated. The study was designed to explore the functional role of NKILA, a newly identified lncRNA, in the progression of NPC. We performed a lncRNA expression profile microarray using four NPC and paired para-cancerous tissues. NKILA was identified as a potential functional lncRNA by this lncRNA expression profile. We used 107 paraffin-embedded NPC tissues with different TNM stages to detect the expression of NKILA and analyzed the survival data by Log-rank test and Cox regression. The role of NKILA and its underlying mechanisms in the progression of NPC were evaluated by a series of experiments in vitro and vivo by silencing or expressing NKILA. Compared with control tissues, NKILA expression was identified to be decreased in NPC tissues. Low NKILA expression was correlated with unfavorable clinicopathological features and predicted poor survival outcome in NPC patients. After adjusting for potential confounders, low expression of NKILA was confirmed to be an independent prognostic factor correlated with poor survival outcomes. Furthermore, we found that NKILA overexpression in high-metastatic-potential NPC cells repressed motile behavior and impaired the metastatic capacity in vitro and in vivo. In contrast, RNAi-mediated NKILA depletion increased the invasive motility of cells with lower metastatic potential. Further experiments demonstrated that NKILA regulated the metastasis of NPC through the NF-κB pathway. Taken together, NKILA plays vital roles in the pathogenesis of NPC. The unique histological characteristics of NPC indicate that local inflammation plays a vital role in carcinogenesis of nasopharyngeal carcinoma.


Assuntos
Carcinogênese/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Nasofaringe/patologia , Prognóstico , RNA Longo não Codificante/genética
16.
Eur Arch Otorhinolaryngol ; 276(11): 3221-3230, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31401760

RESUMO

PURPOSE: We designed this retrospective study to identify predictive value of prognostic nutritional index (PNI) and albumin-globulin ratio (AGR) in nasopharyngeal cancer patients (NPC). METHODS: 95 non-metastatic NPC patients were included in the study. AGR was calculated as the absolute counts between albumin and globulin measurements. (Globulin values were obtained via excluding albumin counts from total protein counts). PNI was calculated using the following formula: [10 × serum albumin value (g/dL) + 0.005 × total lymphocyte count] in the peripheral blood (per mm3). RESULTS: The statistically significant cutoff value of PNI was identified as 45.45 (area under the curve (AUC): 0.636, p = 0.03) for overall survival. The 5-year OS rate for patients with PNI ≤ 45.45 and PNI > 45.45 were 52.9% and 79.0%, respectively. There were statistically significant difference between groups (p = 0.03).The statistically significant cutoff value of AGR was identified as 1.19 (AUC: 0.689, p < 0.01) for overall survival. The 5-year OS rate for patients with AGR ≤ 1.19 and AGR > 1.19 were 57.7% and 82.0%. There were statistically significant differences between the groups (p = 0.04). 5-year OS rate was 42.9% in the high-risk group (low-PNI and low-AGR patients), it was 80.3% in the intermediate group (low PNI and high AGR or high PNI and low AGR) and it was 80.9% in low-risk group (high PNI and high AGR) (p = 0.004). In the multivariate analysis, age and PNI were independent prognostic factors for poorer OS (HR 2.70, 95% CI 1.091-6.719, p = 0.32 and HR 2.44, 95% CI 1.009-5.940, p = 0.48). CONCLUSIONS: Low PNI is independent prognostic factor for poorer OS. Patients with low-PNI and low-AGR have worse survival than patients with high PNI and high AGR.


Assuntos
Globulinas/análise , Contagem de Linfócitos/métodos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Avaliação Nutricional , Albumina Sérica/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Turquia/epidemiologia
17.
Saudi Med J ; 40(8): 755-765, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423511

RESUMO

OBJECTIVES: To analyze the heterogeneous functions of secreted protein acidic and rich in cysteine (SPARC) from different origins and in different tumor microenvironments with the purpose of determining its clinical significance. Methods: The PubMed, CINAHL, Cochrane, Web of Science and Embase databases were utilized. Studies that focused on the effects of SPARC expression on solid tumor progression and clinical implications were used. The different outcomes including overall survival and disease-free survival were analyzed to evaluate their relations with tumor- and stroma-derived SPARC expression. Results: A total of 26 studies including 5,939 patients were enrolled in the present meta-analysis. Tumor-derived SPARC overexpression was significantly related with poor overall survival (hazard ratio: 1.478; 95% CI: 1.143-1.910; p=0.003), and a similar tendency was also observed in disease-free survival (hazard ratio: 1.476; 95% CI: 0.993-2.195; p=0.054). However, the hazard ratios for overall survival and disease-free survival did not present a statistical trend in stromal SPARC overexpression. Tumor type subgroup analysis revealed marked heterogeneity among outcomes. In pancreatic cancer, SPARC overexpression in the stroma was significantly associated with poorer overall survival and disease-free survival. In colorectal cancer, SPARC overexpression in the stroma was associated with better disease-free survival. Conclusion: For the majority of solid tumors, SPARC in cancer cells may be an unfavorable indicator for long-term survival for patients. As for stromal expression, SPARC indicates a poorer prognosis in pancreatic cancer, but a better disease-free survival in colorectal cancer. Secreted protein acidic and rich in cysteine might be a potential biomarker for solid tumor prognosis.


Assuntos
Neoplasias/metabolismo , Osteonectina/metabolismo , Microambiente Tumoral , Neoplasias do Sistema Biliar/metabolismo , Neoplasias do Sistema Biliar/mortalidade , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/mortalidade , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/mortalidade , Neoplasias/mortalidade , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida
18.
Int J Radiat Oncol Biol Phys ; 105(3): 581-590, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31319091

RESUMO

PURPOSE: Previous studies demonstrated that the radiation therapy, image technology, and the application of chemotherapy have developed in the last 2 decades. This study explored the survival trends and treatment failure patterns of patients with nonmetastatic nasopharyngeal carcinoma (NPC) treated with radiation therapy. Furthermore, we evaluated the survival benefit brought by the development of radiation therapy, image technology, and chemotherapy based on a large cohort from 1990 to 2012. METHODS AND MATERIALS: Data from 20,305 patients with nonmetastatic NPC treated between 1990 and 2012 were analyzed. Patients were divided into 4 calendar periods (1990-1996, 1997-2002, 2003-2007, and 2008-2012). Overall survival (OS) was the primary endpoint. RESULTS: Magnetic resonance imaging has replaced computed tomography as the most important imaging technique since 2003. Conventional 2-dimensional radiation therapy, which was the main radiation therapy technique in our institution before 2008, was replaced by intensity modulated radiation therapy later. An increasing number of patients have undergone chemotherapy since 2003. The 5-year OS across the 4 calendar periods increased at each TNM stage with progression-free survival (PFS) and locoregional relapse-free survival (LRFS) showing a similar trend, whereas distant metastasis-free survival showed small differences. Multivariate analyses showed that the application of intensity modulated radiation therapy and magnetic resonance imaging were independent protective factors in OS, PFS, LRFS, and distant metastasis-free survival. Chemotherapy benefited patients in OS, PFS, and LRFS. The main pattern of treatment failure shifted from recurrence to distant metastasis. CONCLUSIONS: The development of radiation therapy, image technology, and chemotherapy increased survival rates among patients with NPC because of excellent locoregional control. Distant failure has become the greatest challenge for NPC treatment.


Assuntos
Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Estudos de Coortes , DNA Viral/sangue , Feminino , Humanos , Imagem por Ressonância Magnética/mortalidade , Imagem por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Papillomaviridae/genética , Prognóstico , Intervalo Livre de Progressão , Radioterapia/métodos , Radioterapia/mortalidade , Radioterapia/tendências , Radioterapia de Intensidade Modulada/mortalidade , Radioterapia de Intensidade Modulada/tendências , Taxa de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X/tendências , Falha de Tratamento , Adulto Jovem
19.
PLoS One ; 14(7): e0219611, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291379

RESUMO

BACKGROUND: At present, the management of nasopharyngeal carcinoma (NPC) is mainly based on radiotherapy, but there are many radiation delivery techniques such as intensity-modulated radiotherapy (IMRT) and 2-dimensional radiotherapy (2D-RT). MATERIALS AND METHODS: We searched all the eligible studies through the PubMed, Cochrane Library, Medline, and Embase. The endpoint events in meta-analysis were overall survival (OS), tumor local control including local-regional free survival (LRFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS), and late toxicities. RESULTS: A total of ten publications met the criteria and were identified through searches of the databases and references. We included 13304 patients in the meta-analysis, of whom 5212 received IMRT and 8092 were allocated to 2D-RT alone group. Compared with 2D-RT treatment, the IMRT group was associated with a better 5-year OS (OR = 1.70; 95% CI = 1.36-2.12), LRFS (OR = 2.08; 95% CI = 1.82-2.37), and PFS (OR = 1.40; 95% CI = 1.26-1.56). Additionally, the incidence of late toxicities such as late xerostomia (OR = 0.21; 95% CI = 0.09-0.51), trismus (OR = 0.16; 95% CI = 0.04-0.60), and temporal lobe neuropathy (TLN) (OR = 0.40; 95% CI = 0.24-0.67) for NPC patients in IMRT group were significantly lower than 2D-RT. CONCLUSIONS: The meta-analysis demonstrates that IMRT provides improved long-term tumor overall survival and local control including LRFS and PFS. Additionally, IMRT yields a lower incidence of late toxicities induced by irradiation in NPC patients. Compared to 2D-RT, IMRT may be an effective treatment for patients with NPC. Further intensive studies should be pursued to examine the association.


Assuntos
Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia/epidemiologia , Lesões por Radiação/epidemiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Intervalo Livre de Doença , Humanos , Incidência , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Lesões por Radiação/etiologia , Fatores de Tempo
20.
Br J Radiol ; 92(1102): 20190209, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31265322

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignancy with unique clinical biological profiles such as associated Epstein-Barr virus infection and high radiosensitivity. Radiotherapy has long been recognized as the mainstay for the treatment of NPC. However, the further efficacy brought by radical radiotherapy has reached the bottleneck in advanced patients, who are prone to develop recurrence and distant metastasis after treatment. The application of photon therapy makes it possible for radiation dose escalation in refractory cases and may provide second chance for recurrent patients with less unrecoverable tissue damage. The concept of adaptive radiotherapy is put forward in consideration of target volume shrinkage during treatment. The replanning procedure offers better protection for the organ at risk. However, the best timing and candidates for adaptive radiotherapy is still under debate. The current tendency of artificial intelligence in NPC mainly focuses on image recognition, auto-segmentation and dose prediction. Although artificial intelligence is still in developmental stage, the future of it is promising.To further improve the efficacy of NPC, multimodality treatment is encouraged. In-depth studies on genetic and epigenetic variations help to explain the great heterogeneity among patients, and could further be applied to precise screening and prediction, personalized radiotherapy and the evolution of targeted drugs. Given the clinical benefit of immunotherapy in other cancers, the application of immunotherapy, especially immune checkpoint inhibitor, in NPC is also of great potential. Results from ongoing clinical trials combining immunotherapy with radiotherapy in NPC are expected.


Assuntos
Inteligência Artificial , Previsões , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Inteligência Artificial/tendências , Humanos , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/mortalidade , Órgãos em Risco/efeitos da radiação , Medicina de Precisão/métodos , Terapia com Prótons/métodos , Lesões por Radiação/prevenção & controle , Radioterapia/métodos , Radioterapia de Intensidade Modulada/métodos
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