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1.
JAMA Netw Open ; 4(9): e2124721, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34554238

RESUMO

Importance: Nonanatomic prognostic factors complement the traditional anatomic staging system and could be incorporated into the tumor-node-metastasis (TNM) framework. Several diseases have incorporated nonanatomic prognostic factors into the determination of TNM staging groups. Objective: To refine TNM staging groups for Epstein-Barr virus (EBV)-related nonmetastatic nasopharyngeal carcinoma (NPC) by incorporating EBV DNA status. Design, Setting, and Participants: This multicenter prognostic study included patients with NPC treated with radiotherapy at 2 hospitals in China from January 2008 to December 2016. Progression-free survival and overall survival according to EBV DNA status and the TNM staging system were compared. Recursive partitioning analysis (RPA) combined with supervised clustering was applied to derive prognostic groupings, and then a refined RPA staging schema was developed, validated, and compared with existing staging schemes. Statistical analyses were conducted from October 1, 2020, to June 15, 2021. Exposures: Curative intensity-modulated radiotherapy with or without platinum-based chemotherapy. Main Outcomes and Measures: The primary end point was progression-free survival. The performance of the staging system was assessed using the time-dependent area under the receiver operating characteristic curves and the TNM stage system's evaluation methodology. Results: A total of 2354 patients (1709 men [72.6%]; median [interquartile range] age, 45 [38-53] years) were split into training (1372 [58.3%]), internal validation (672 [28.5%]), and external validation (310 [13.2%]) cohorts. Pretreatment EBV DNA was detected in 1338 (56.8%) patients. EBV DNA status was an independent prognostic factor: lower survival probability by higher TNM stage was evident in EBV DNA-positive patients but not in those with EBV DNA-negative disease. After integrating EBV DNA status and TNM stage, nonmetastatic NPC cases were categorized into RPA-I (T1-3N0 or EBV DNA-negative T1-3N1 cancers), RPA-II (EBV DNA-positive T1-3N1-2 or EBV DNA-negative T1-3N2-3/T4N0-3 cancers), and RPA-III (EBV DNA-positive T4N0-3/T1-3N3 cancers) groups, each with distinctly different prognosis. This system of RPA staging outperformed the current TNM stage system and 2 reported RPA staging schemes. These results were internally and externally validated. Conclusions and Relevance: An RPA-based staging system for EBV-related NPC cases was associated with improved outcomes. This staging system may facilitate prognostic stratification and clinical trial designs.

2.
Front Neurosci ; 15: 745227, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557073

RESUMO

Aging, an irreversible and unavoidable physiological process in all organisms, is often accompanied by obesity, diabetes, cardiovascular diseases, sleep disorders, and fatigue. Thus, older adults are more likely to experience metabolic symptoms and sleep disturbances than are younger adults. Restricted feeding (RF) is a dietary regimen aimed at improving metabolic health and extending longevity, as well as reorganizing sleep-wake cycles. However, the potential of RF to improve metabolic health and sleep quality in older adults who are known to show a tendency toward increased weight gain and decreased sleep is unknown. To elucidate this issue, aged mice were assigned to an RF protocol during the active phase for 2 h per day for 2 weeks. Sleep-wake cycles were recorded during the RF regime in RF group and control mice. At the end of this period, body weight and blood biochemistry profiles, including blood glucose, cholesterol, and enzyme activity, in addition to dopamine concentrations in the brain, were measured in the RF group and age-matched controls. RF for 2 weeks improved the metabolic health of aged mice by reducing their body weights and blood glucose and cholesterol levels. At the beginning of the RF regime, sleep decreased in the dark period but not in the light period. After stable food entrainment was achieved (7 days post-RF commencement), the amount of time spent in wakefulness during the light period dramatically increased for 2 h before food availability, thereby increasing the mean duration of awake episodes and decreasing the number of wakefulness episodes. There was no significant difference in the sleep-wake time during the dark period in the RF group, with similar total amounts of wakefulness and sleep in a 24-h period to those of the controls. During the RF regime, dopamine levels in the midbrain increased in the RF group, pointing to its potential as the mechanism mediating metabolic symptoms and sleep-wake regulation during RF. In conclusion, our study suggested that RF during aging might prohibit or delay the onset of age-related diseases by improving metabolic health, without having a severe deleterious effect on sleep.

3.
Am J Cancer Res ; 11(8): 3946-3955, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522460

RESUMO

Nasopharyngeal carcinoma (NPC) is highly incident in southern China. Distant metastasis is the leading cause of death in NPC patients. However, the phenotypical feature of this patient population is largely undefined. The current study aimed to categorize metastatic NPC patients into novel subgroups based on their EBV DNA trajectories. In this retrospective study, 446 eligible patients with metastatic NPC treated at Sun Yat-Sen University Cancer Center between 2012 and 2016 were analyzed. Using a mixture model analysis, we identified distinct trajectories based on longitudinal EBV DNA measurements. We evaluated their associations with metastatic NPC mortality using Cox regression analysis. The two-class trajectory model provided the best fit, in which 272 patients were classified as non-sustained EBV DNA class and 174 patients as sustained EBV DNA class. After a median follow-up of 60.8 months, the median OS was 61.7 months in the sustained EBV DNA clearance class versus 20.0 months in the non-sustained EBV DNA clearance class (P<0.001). Compared with patients in the non-sustained EBV DNA clearance class, patients in the sustained EBV DNA clearance class demonstrated superior PFS (HR, 3.238; 95% CI, 2.601-4.032; P<0.001). Forty-three patients experienced disease-free for longer than 36 months, defined as long-term survivors (LTS). Notably, 41 patients were presented in the sustained EBV DNA clearance class (95.3%), along with only 2 patients in the non-sustained EBV DNA clearance class. Collectively, we identified two EBV DNA trajectory sub-phenotypes of patients with metastatic NPC, providing more reliable survival information for physicians and patients during their informed decision-making process.

4.
Clin Cancer Res ; 27(15): 4186-4194, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34083231

RESUMO

PURPOSE: Previous studies suggest that a cumulative cisplatin dose of 200 mg/m2 might be adequate in the intensity-modulated radiation therapy (IMRT) era for locoregionally advanced nasopharyngeal carcinoma (LANPC). However, two cycles of once-every-3-weeks cisplatin at 100 mg/m2 has never been prospectively compared with standard once-a-week cisplatin regimen. PATIENTS AND METHODS: This trial was conducted at three hospitals from 2011 to 2016. Patients who met the eligibility criteria were recruited (ChiCTR-TRC-12001979) and randomly assigned (1:1) via a computer-generated sequence to receive once-every-3-weeks cisplatin at 100 mg/m2 for two cycles or once-a-week cisplatin at 40 mg/m2 for six cycles concurrently with IMRT. Primary endpoint was failure-free survival and between-group absolute difference of 10% as the noninferiority margin. RESULTS: A total of 510 patients were enrolled. Median follow-up time was 58.3 months with 85.4% of 3-year failure-free survival in the once-every-3-weeks group and 85.6% in the once-a-week group. An absolute difference of -0.2% (95% confidence interval, -6.3 to 5.9; P noninferiority = 0.0016). Acute toxicities of grade 3 or higher occurred in 55.8% in the once-every-3-weeks group and 66.3% in the once-a-week group (P = 0.015). The most common acute toxicities were hematologic abnormalities, including leukopenia (16% vs. 27%; P = 0.0022) and thrombocytopenia (1% vs. 5%; P = 0.015). The late grade 3-4 auditory loss rate was significantly lower in the once-every-3-weeks group than the once-a-week group (6% vs. 13%; P = 0.0039). CONCLUSIONS: Once-every-3-weeks cisplatin as concurrent chemoradiotherapy is noninferior to once-a-week cisplatin in the treatment efficacy in the LANPC. Although both regimens are well tolerated, severe acute toxicities and late-onset auditory loss are higher in the once-a-week group.

5.
J Inflamm Res ; 14: 2225-2237, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079329

RESUMO

Purpose: We sought to assess the prognostic and predictive value of a circulating inflammation signature (CISIG) and develop CISIG-based tools for predicting prognosis and guiding individualized induction chemotherapy (ICT) in non-metastatic nasopharyngeal carcinoma (NPC). Patients and Methods: We retrospectively collected a candidate inflammatory biomarker panel from patients with NPC treated with definitive radiotherapy between 2012 and 2017. We developed the CISIG using candidate biomarkers identified by a least absolute shrinkage and selection operator (LASSO) Cox regression model. The Cox regression analyses were used to evaluate the CISIG prognostic value. A CISIG-based prediction model was constructed, validated, and assessed. Potential stratified ICT treatment effects were examined. Results: A total of 1149 patients were analyzed. Nine biomarkers selected by LASSO regression in the training cohort were used to construct the CISIG, including hyaluronidase, laminin, procollagen III, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, high-density lipoprotein, lactate dehydrogenase, and C-reactive protein-to-albumin ratio. CISIG was an independent prognostic factor for disease-free survival (DFS; hazard ratio: 2.65, 95% confidence interval: 1.93-3.64; P < 0.001). High CISIG group (>-0.2) was associated with worse 3-year DFS than low CISIG group in both the training (67.5% vs 88.3%, P < 0.001) and validation cohorts (72.3% vs 85.1%, P < 0.001). We constructed and validated a CISIG-based nomogram, which showed better performance than the clinical stage and Epstein-Barr virus DNA classification methods. A significant interaction between CISIG and the ICT treatment effect was observed (P for interaction = 0.036). Patients with high CISIG values did not benefit from ICT, whereas patients with low CISIG values significantly benefited from ICT. Conclusion: The developed CISIG, based on a circulating inflammatory biomarker panel, adds prognostic information for patients with NPC. The proposed CISIG-based tools offer individualized risk estimation to facilitate suitable ICT candidate identification.

6.
Lancet Oncol ; 22(5): 716-726, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33857411

RESUMO

BACKGROUND: Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. METHODS: In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18-60 years with previously untreated, non-keratinising stage III-IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68-70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62-68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30-32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed. FINDINGS: From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9-81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7-80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69-1·39; log-rank p=0·92), with a difference of 0·5% (95% CI -7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (-6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3-4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported. INTERPRETATION: Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma. FUNDING: National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Adulto , Ciclobutanos/administração & dosagem , Ciclobutanos/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Dosagem Radioterapêutica
7.
J Inflamm Res ; 14: 817-828, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732007

RESUMO

Purpose: We aimed to develop a simple scoring system based on baseline inflammatory and nutritional parameters to predict the efficacy of first-line chemotherapy and survival outcomes for de novo metastatic nasopharyngeal carcinoma (mNPC). Patients and Methods: We retrospectively collected ten candidate inflammatory and nutritional parameters from de novo mNPC patients who received platinum-based first-line chemotherapy treatment. We examined the effects of these ten candidate variables on progression-free survival (PFS) using the Cox regression model. We built a risk-scoring system based on the regression coefficients associated with the identified independent prognostic factors. The predictive accuracy of the scoring system was evaluated and independently validated. Results: A total of 460 patients were analyzed. Four independent prognostic factors were identified in a training cohort and were used to construct the scoring system, including nutritional risk index, C-reactive protein level, alkaline phosphatase level, and lactate dehydrogenase level. Based on the score obtained from the scoring system, we stratified patients into three prognostic subgroups (low: 0-1 point, intermediate: 2-3 points, and high: 4 points) associated with significantly different disease control rates (94.7% vs. 92.5% vs. 66.0%, respectively) and survival outcomes (3-year PFS: 55.8% vs. 29.1% vs. 11.9%, respectively). The scoring system had a good performance for the prediction of short-term disease control (area under the receiver operating characteristic curve [AUC]: 0.701) and long-term survival outcomes (time-dependent AUC for 5-year PFS: 0.713). The results were internally validated using an independent cohort (AUC for predicting disease control: 0.697; time-dependent AUC for 5-year PFS: 0.713). Conclusion: We developed and validated a clinically useful risk-scoring system that could predict the efficacy of first-line chemotherapy and survival outcomes in de novo mNPC patients. This system may help clinicians to design personalized treatment strategies.

8.
Biol Sex Differ ; 12(1): 18, 2021 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-33516267

RESUMO

BACKGROUND: The mortality of nasopharyngeal carcinoma (NPC) is usually lower in females than in males, but the underlying mechanism remains largely unknown. We sought to describe the age-dependent patterns of gender disparities in NPC survival and explore the extent to which the confounder or mediation effects could explain these differences. METHODS: A total of 11,980 patients with NPC were reviewed. The effect of gender on cancer-specific survival (CSS) was assessed using Cox regression analyses. Two propensity score methods were conducted to control the confounding bias between genders. Restricted cubic spline regression was used to model the association of gender and age with mortality flexibly. Multiple mediation analysis was applied to estimate the direct or indirect effect of gender on CSS. RESULTS: Overall, 7026 males and 2320 females were analyzed. The crude CSS was significantly higher for females than males (10-year CSS 78.4% vs 70.3%; P < 0.001). Similar results were observed after adjusting for confounding bias. Gender disparities in NPC-specific mortality were age-dependent, where they would increase with age until peaking at age 55-60 years and decline rapidly afterward. Subgroup analyses revealed that females' survival advantage was observed in the 18-45 age group and was more prominent in the 46-55 age group, but vanished in the > 55 age group. Either confounder or mediation effects only accounted for approximately 20% of the gender differences. CONCLUSIONS: Gender disparities in cancer-specific mortality for patients with NPC were age-dependent. The differences mostly cannot be explained by confounder or mediation effects.


Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Fatores Sexuais
9.
Int J Radiat Oncol Biol Phys ; 109(1): 120-130, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32853711

RESUMO

PURPOSE: We aimed to develop an accurate prognostic model to identify suitable candidates for definitive radiation therapy (DRT) in addition to palliative chemotherapy (PCT) among patients with de novo metastatic nasopharyngeal carcinoma (mNPC). METHODS AND MATERIALS: Patients with de novo mNPC who received first-line PCT with or without DRT were included. Overall survival for patients who received PCT alone versus PCT plus DRT was estimated using inverse probability of treatment weighting-adjusted survival analyses. We developed and validated a prognostic model to predict survival and stratify risks in de novo mNPC. A model-based trees approach was applied to estimate stratified treatment effects using prognostic scores obtained from the prognostic model and to identify suitable DRT candidates. Dominance analysis was used to determine the relative importance of each predictor of receiving DRT. RESULTS: A total of 460 patients were enrolled; 244 received PCT plus DRT and 216 received PCT alone. The 6-month conditional landmark, inverse probability of treatment weighting-adjusted Cox regression analysis showed that PCT plus DRT was associated with a significant survival benefit (hazard ratio: 0.516; 95% confidence interval, 0.403-0.660; P < .001). A prognostic model based on 5 independent prognostic factors, including serum lactate dehydrogenase, number of metastatic sites, presence of liver metastasis, posttreatment Epstein-Barr virus DNA level, and response of metastases to chemotherapy was developed and subsequently validated. Prognostic scores obtained from the prognostic model were used for risk stratification and efficacy estimation. High-risk patients identified using the proposed model would not benefit from additional DRT, whereas low-risk patients experienced significant survival benefits. Socioeconomic factors, including insurance status and education level, played an important role in receipt of DRT. CONCLUSIONS: Additional DRT after PCT was associated with increased overall survival in patients with de novo mNPC, especially low-risk patients identified with a newly developed prognostic model.


Assuntos
Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/radioterapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/diagnóstico , Metástase Neoplásica , Prognóstico
11.
Oncogene ; 39(30): 5307-5322, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32555330

RESUMO

Nasopharyngeal carcinoma (NPC) is a unique head and neck cancer with highly aggressive and metastatic potential in which distant metastasis is the main reason for treatment failure. Till present, the underlying molecular mechanisms of NPC metastasis remains poorly understood. Here, we identified S100 calcium-binding protein A14 (S100A14) as a functional regulator suppressing NPC metastasis by inhibiting the NF-kB signaling pathway and reversing the epithelial-mesenchymal transition (EMT). S100A14 was found to be downregulated in highly metastatic NPC cells and tissues. Immunohistochemical staining of 202 NPC samples revealed that lower S100A14 expression was significantly correlated with shorter patient overall survival (OS) and distant metastasis-free survival (DMFS). S100A14 was also found as an independent prognostic factor for favorable survival. Gain- and loss-of-function studies confirmed that S100A14 suppressed the in vitro and in vivo motility of NPC cells. Mechanistically, S100A14 promoted the ubiquitin-proteasome-mediated degradation of interleukin-1 receptor-associated kinase 1 (IRAK1) to suppress NPC cellular migration. Moreover, S100A14 and IRAK1 established a feedback loop that could be disrupted by the IRAK1 inhibitor T2457. Overall, our findings showed that the S100A14-IRAK1 feedback loop could be a promising therapeutic target for NPC metastasis.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Quinases Associadas a Receptores de Interleucina-1/genética , Neoplasias Pulmonares/genética , NF-kappa B/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos Nus , NF-kappa B/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Interferência de RNA , Transdução de Sinais/genética , Análise de Sobrevida
12.
Radiother Oncol ; 145: 101-108, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31931288

RESUMO

BACKGROUND AND PURPOSE: To evaluate the prognostic value of MRI-detected residual retropharyngeal lymph node (RRLN) at three months after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) and second, to establish a nomogram for the pretherapy prediction of RRLN. MATERIALS AND METHODS: We included 1103 patients with NPC from two hospitals (Sun Yat-Sen University Cancer Center [SYSUCC, n = 901] and Dongguan People's Hospital [DGPH, n = 202]). We evaluated the prognostic value of RRLN using Cox regression model in SYSUCC cohort. We developed a nomogram for the pretherapy prediction of RRLN using logistic regression model in SYSUCC training cohort (n = 645). We assessed the performance of this nomogram in an internal validation cohort (SYSUCC validation cohort, n = 256) and an external independent cohort (DGPH validation cohort, n = 202). RESULTS: RRLN was an independent prognostic factor for OS (HR 2.08, 95% CI 1.32-3.29), DFS (HR 2.45, 95% CI 1.75-3.42), DMFS (HR 3.31, 95% CI 2.15-5.09), and LRRFS (HR 3.04, 95% CI 1.70-5.42). We developed a nomogram based on baseline Epstein-Barr virus DNA level and three RLN status-related features (including minimum axial diameter, extracapsular nodal spread, and laterality) that predicted an individual's risk of RRLN. Our nomogram showed good discrimination in the training cohort (C-index = 0.763). The favorable performance of this nomogram was confirmed in the internal and external validation cohorts. CONCLUSION: MRI-detected RRLN at three months after IMRT was an unfavorable prognostic factor for patients with NPC. We developed and validated an easy-to-use nomogram for the pretherapy prediction of RRLN.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Herpesvirus Humano 4 , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Estadiamento de Neoplasias , Nomogramas , Prognóstico , Estudos Retrospectivos
13.
Cancer Med ; 9(3): 920-930, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31834990

RESUMO

BACKGROUND: To explore the prognostic value of early radiological response (ERR) to first-line platinum-containing chemotherapy in patients with metastatic nasopharyngeal carcinoma (mNPC), as well as its correlation with the best radiological response (BRR). PATIENTS AND METHODS: A total of 756 mNPC patients with measurable lesions who received first-line platinum-containing chemotherapy were enrolled in this study. ERR was defined as complete or partial response after 6 weeks of chemotherapy according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. We performed survival analyses according to the radiological response after repeated chemotherapy. Log-rank test and Cox regression were used to analyze the survival data. RESULTS: About 470 patients achieved ERR and 78 patients achieved subsequent response (objective response after repeated chemotherapy). ERR patients had better OS (P < .001, median OS: 34.3 vs 22.2 months) and PFS (P < .001, median PFS: 10.2 vs 7.4 months) than non-ERR ones. ERR (OS: HR = 0.591, 95% CI, 0.495-0.705, P < .001, PFS: HR = 0.586, 95% CI, 0.500-0.686, P < .001) was independently prolonged survival compared with non-ERR ones. Besides, ERR was significantly correlated with the BRR (Kappa: 0.73; Pearson: 0.74, P < .001), and had significantly longer OS and PFS than patients with subsequent response, respectively. CONCLUSION: ERR is an independent prognostic factor in determining survival in mNPC patients received first-line platinum-containing chemotherapy, which may be a more sensitive predictor to assess overall efficacy of systemic treatment than BRR in mNPC. Prospective validation studies are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Nasofaringe/diagnóstico por imagem , Critérios de Avaliação de Resposta em Tumores Sólidos , Adulto , Cisplatino/uso terapêutico , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/secundário , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Nasofaringe/patologia , Prognóstico , Intervalo Livre de Progressão , Estudos Prospectivos , Cintilografia , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
14.
Hypertens Res ; 42(11): 1745-1756, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31273339

RESUMO

Appropriate exercise training (ExT) has been shown to decrease high blood pressure. Accumulating data have indicated the beneficial effects of ExT on prehypertension. This study tested whether prehypertension ExT protects against hypertension and cardiac remodeling in spontaneously hypertensive rats (SHR) and explored the underlying mechanisms by examining the cardiac angiotensin-converting enzyme (ACE) and ACE2 signaling axes. Low-intensity ExT was started in male SHR and control Wistar-Kyoto rats prior to the onset of hypertension and maintained for 8 or 16 weeks. Blood pressure (BP) was measured biweekly by the tail-cuff method. Cardiac function and remodeling were assessed, and changes in the ACE and ACE2 axes were examined after the final ExT session. The results showed that prehypertension ExT slowed the onset and progression of hypertension in SHR. In parallel, hypertrophy in the hearts of hypertensive rats was attenuated, myocardial fibrosis was reduced, and impairment of left ventricular diastolic function was reduced. In the SHR myocardium, the levels of components involved in the ACE-Ang II-AT1 axis were homogeneously and progressively increased, whereas those involved in the ACE2-Ang(1-7)-MAS axis were heterogeneously decreased. Different temporal responses were observed for the key effectors Ang II and Ang(1-7). Myocardial Ang II levels were progressively increased in SHR and were consistently reduced by ExT. By contrast, Ang(1-7) decreased only after 16 weeks of sedentariness, and this decrease was abolished by ExT. In addition, 16 weeks of ExT increased the levels of Ang(1-7) in normotensive control rats. In summary, prehypertension ExT attenuates hypertension and cardiac remodeling. Downregulation of Ang II seems to serve as a protective mechanism during ExT, while upregulation of Ang(1-7) is induced after a relatively long period of ExT.


Assuntos
Cardiomegalia/prevenção & controle , Condicionamento Físico Animal/fisiologia , Pré-Hipertensão/terapia , Angiotensina I/metabolismo , Angiotensina II/metabolismo , Enzima de Conversão de Angiotensina 2 , Animais , Pressão Sanguínea , Diástole , Masculino , Miocárdio/enzimologia , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Remodelação Ventricular
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(12): 994-1001, 2018 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-30572987

RESUMO

OBJECTIVE: To investigate the physical development of Uygur and Han neonates in Urumqi, China. METHODS: Live singleton neonates with a gestational age of 28-42 weeks who were born in the First Affiliated Hospital of Xinjiang Medical University and Maternal and Child Health Care Hospital from December 2014 to May 2017 were enrolled, and their body weight, body length, head circumference, and chest circumference at birth were measured. The cubic curve fitting method was used to plot the smooth curves of body weight, body length, head circumference, and chest circumference. RESULTS: A total of 5 027 singleton neonates with a gestational age of 28-42 weeks were enrolled, with 2 625 boys and 2 402 girls. The average values of birth weight, body length, head circumference, and chest circumference, Quetelet index, and Ververck index of Uygur/Han boys and girls with a gestational age of 28-42 weeks were obtained, and related smoothed percentile curves were plotted. There were some differences between Uygur and Han neonates in the average values of some growth and development indices. The Quetelet index and the Ververck index of Uygur and Han neonates increased with the increase in gestational age, and the Uygur neonates had a higher Ververck index than the Han neonates. CONCLUSIONS: There are differences in the levels of some growth and development indices and Ververck index between the Uygur and Han neonates in Urumqi. The average values of body weight, body length, chest circumference, and head circumference at birth, Quetelet index, and Ververck index of Uygur and Han neonates with a gestational age of 28-42 weeks and their smoothed percentile curves can provide a reference for the assessment of neonatal growth and development in Urumqi.


Assuntos
Peso ao Nascer , Estatura , China , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino
16.
J Cancer ; 9(17): 3023-3031, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30210624

RESUMO

Purpose: To date, no guidelines exist for elderly nasopharyngeal carcinoma (NPC) patients (60 years of age or older) due to a lack of prospective clinical trials. This study evaluated the efficacy of concurrent chemotherapy (CCRT) for NPC in elderly patients treated with intensity-modulated radiotherapy (IMRT). Methods: Patients were identified from a prospectively maintained database. A total of 198 consecutive cases of elderly patients with NPC receiving IMRT, including 103 patients treated with IMRT plus CCRT and 95 patients treated with IMRT alone, were analysed from January 2002 to December 2013. Multivariate analysis (MVA) using the Cox proportional hazards model and propensity score analysis (PSA) were performed for overall survival (OS) and disease-free survival (DFS). Finally, sensitivity analysis was performed. Results: The median follow-up time was 55.3 months (range, 3-135.6 months). In the entire cohort, both MVA and PSA models showed that compared with IMRT alone, IMRT plus CCRT significantly improved survival (hazard ratio [HR] 2.143, 95% confidence interval [95% CI] 1.180-3.890; HR 1.961, 95% CI, 1.117-3.443, for OS and DFS, respectively). Similar results were found in the subgroups with high levels of Epstein-Barr virus (EBV) DNA, except in the low-EBV-DNA cohort. The total rates of severe acute toxicity, including leukopenia, neutropenia, stomatitis, and emesis, were significantly higher in the IMRT+CCRT group than in the IMRT-alone group (P < 0.001) but were similar to the rates of severe late toxicity (P = 0.818). Sensitivity analysis confirmed the robustness of our analysis. Conclusions: In the era of IMRT, CCRT retained survival benefits at high EBV DNA levels but not at low EBV DNA levels for elderly NPC patients. Randomized clinical trials are needed to confirm our findings.

17.
Ther Adv Med Oncol ; 10: 1758835918782331, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30046357

RESUMO

Background: In the intensity-modulated radiotherapy (IMRT) era, the survival benefit of concurrent chemotherapy for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains undetermined. This study aimed to evaluate the benefits of IMRT with concurrent chemotherapy compared with IMRT alone for LA-NPC patients with different plasma Epstein-Barr virus (EBV) DNA levels. Methods: Patients were identified from a prospectively maintained database in an endemic area between November 2002 and December 2013. Cox proportional hazards models, propensity score matching, and inverse probability weighting models were established for survival analysis. Stratification analysis was performed based on interaction effects analysis. Finally, sensitivity analysis was performed considering unmeasured confounders. Results: A total of 1357 eligible patients were enrolled (median follow up 62.4 months; range 3.5-155.8 months). No significant survival differences were observed between groups in the entire cohort. Notably, a significant interaction effect was observed between treatment regimens and EBV DNA levels. In patients with high EBV DNA levels (>4000 copies/ml), all three models showed that IMRT with concurrent chemotherapy significantly improved overall survival [hazard ratio (HR) 2.521, 95% confidence interval (CI) 1.218-5.216], disease-free survival (HR 2.168, 95% CI 1.349-3.483), and distant metastasis-free survival (HR 2.331, 95% CI 1.194-4.551) compared with IMRT alone. No differences were found in patients with low EBV DNA levels. Sensitivity analysis confirmed the robustness of the results. Conclusion: In the IMRT era, concurrent chemotherapy treatment of LA-NPC patients with high EBV DNA levels is reasonable. However, the optimal regimen for LA-NPC patients with low EBV DNA levels needs further validation in randomized clinical trials.

18.
Cancer Commun (Lond) ; 38(1): 21, 2018 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-29764487

RESUMO

BACKGROUND: Available data in the literature comparing different induction chemotherapy (IC) regimens on locoregionally advanced nasopharyngeal carcinoma (NPC) are scarce. The purpose of the present study was to evaluate the outcomes of locoregionally advanced NPC patients who were treated with taxane, cisplatin and 5-fluorouracil (TPF) or cisplatin and 5-fluorouracil (PF) as IC followed by concurrent chemoradiotherapy (CCRT). METHODS: In total, 1879 patients with locoregionally advanced NPC treated with IC and CCRT from a prospectively maintained database were included in the present observational study. We compared overall survival (OS), disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival, using the propensity score method. RESULTS: In total, 1256 patients received TPF or PF as IC backbone. The TPF group showed significantly better OS (hazard ratio [HR], 0.660; 95% confidence interval [CI] 0.442-0.986; P = 0.042), DSS (HR, 0.624; 95% CI 0.411-0.947; P = 0.027) and DMFS (HR, 0.589; 95% CI 0.406-0.855; P = 0.005) compared with the PF group in multivariable analyses. Propensity score matching identified 294 patients in each cohort and confirmed that TPF was associated with significantly improved 5-year OS (88.1% vs. 80.7%; P = 0.042), DSS (88.5% vs. 80.7%; P = 0.021) and DMFS (87.9% vs. 78.6%; P = 0.012) rates compared with the PF group. There were no significant differences in locoregional relapse-free survival before or after matching. CONCLUSIONS: In our study, IC with the TPF regimen combined with CCRT showed improved long-term survival for the patients with locoregionally advanced NPC compared with the PF regimen. However, a prospective randomized clinical trial to validate these findings is necessary.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Náusea/etiologia , Recidiva Local de Neoplasia , Neutropenia/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Vômito/etiologia
19.
J Exp Clin Cancer Res ; 37(1): 85, 2018 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-29665837

RESUMO

BACKGROUND: Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear. METHODS: Quantitative RT-PCR (qRT-PCR), western blotting, cell growth, foci formation, migration and invasion assays, and xenograft mouse models were utilized to examine the expression levels and functions of the CXCL5/CXCR2 axis in NPC. A luciferase reporter assay, western blotting, immunofluorescence, and migration and invasion assays were used to identify and verify the ERK/GSK-3ß/Snail signalling pathway. RESULTS: CXCL5 was significantly increased in the sera of NPC patients, and high expression levels of CXCL5/CXCR2 in NPC primary tissues indicated poor survival. CXCL5 and CXCR2 were upregulated in NPC cell lines. Ectopic expression of the CXCL5/CXCR2 axis promoted NPC cell migration and invasion in vitro and the formation of lung metastases in vivo. Mechanistically, the dual overexpression of CXCL5 and CXCR2 promoted cell spreading by inducing the epithelial-mesenchymal transition (EMT) through the activation of the ERK/GSK-3ß/Snail signalling pathway. CONCLUSION: The CXCL5/CXCR2 axis contributes to the EMT of NPC cells by activating ERK/GSK-3ß/Snail signalling, and this axis may be a potential diagnostic marker and therapeutic target for patients with NPC.


Assuntos
Quimiocina CXCL5/genética , Glicogênio Sintase Quinase 3 beta/genética , Carcinoma Nasofaríngeo/genética , Animais , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Humanos , Camundongos , Carcinoma Nasofaríngeo/metabolismo , Prognóstico , Transdução de Sinais
20.
PLoS One ; 12(8): e0182963, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28797119

RESUMO

BACKGROUND: To evaluate the clinical characteristics, treatment-related toxicities and survival in patients with nasopharyngeal carcinoma (NPC) with or without oropharyngealcandidiasis (OPC) during radiotherapy. METHODS: The current study was conducted with NPC patients undergoing radiotherapy at Sun Yat-Sen University Cancer Center between June 2011 and May 2012. A clinical diagnosis of candidiasis was determined on the basis of a positive potassium hydroxide (KOH) test and the presence of pseudomembranous (white) form of candidal overgrowth. The Cox proportional hazard regression model was used to test the association of OPC and related survival rates. RESULTS: Compared with the non-OPC group, the OPC group had significantly increased occurrence rates of grade 3-4 mucositis (14.5% vs. 7.4%, P = 0.049), anaemia (11.3% vs. 4.4%, P = 0.020), hepatotoxicity (4.8% vs. 1.1%, P = 0.021) and critical weight loss (85.5% vs. 56.6%, P<0.001) during radiotherapy. The OPC group had a significantly lower disease-free survival (DFS) (70.9% vs. 82.6%, P = 0.012), mainly as a result of a reduction in locoregional relapse-free survival (LRFS) (87.0%vs. 94.9%, P = 0.025). After stratification by T stage, the 5-year DFS in T3-4 patients were 82.0% and 68.8% in non-OPC and OPC groups, respectively (P = 0.022). Multivariate analyses indicated that OPC was a prognostic factor for LRFS and DFS. CONCLUSIONS: OPC during radiotherapy may worsen the nutritional status of NPC patients according to weight loss and anaemia, leading to a negative impact on 5-year locoregional relapse-free survival and disease-specific survival. Further investigations are needed to explore whether prevention and treatment of OPC during radiotherapy will be useful.


Assuntos
Candidíase/complicações , Carcinoma/complicações , Carcinoma/radioterapia , Neoplasias Nasofaríngeas/complicações , Neoplasias Nasofaríngeas/radioterapia , Nasofaringe/efeitos da radiação , Adulto , Candida/isolamento & purificação , Candidíase/diagnóstico , Carcinoma/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
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