Search

Purpose Clinical Trials have emerged as the main force in driving the development of medicine. However, little is known about the current status of clinical trials regarding nasopharyngeal carcinoma (NPC). This study aimed at providing a comprehensive landscape of NPC-related trials on the basis of ClinicalTrials.gov database. Patients and methods We used the keyword “nasopharyngeal carcinoma” to search the ClinicalTrials.gov database and assessed the characteristics of these trials. Results Up to December 30, 2016, 462 eligible trials in total were identified, of which 222 (48.0%) recruited only NPC (NPC trials) and the other 240 (52.0%) recruited both NPC and other cancers (multiple cancer trials). Moreover, 47 (10.2%) were Epstein-Barr virus (EBV)-related trials and 267 (57.8%) focused on metastatic/recurrent disease. Compared with NPC trials, the multiple cancer trials had a higher percentage of phase 1 (26.7% vs. 6.7%, P < 0.001) studies and more patients with metastatic/recurrent disease (72.5% vs. 41.9%, P < 0.001). Notably, non-EBV trials had more phase 2 or 3 (78.4% vs. 48.8%, P < 0.001) and interventional studies (89.5% vs. 70.7%, P = 0.002) than EBV trials. Obviously, more phase 2/3 or 3 trials were conducted in patients with non-metastatic/recurrent disease (29.4% vs. 4.9%, P < 0.001); however, metastatic/recurrent trials were more likely to be anticancer (94.6% vs. 63.6%, P < 0.001). Conclusions The role of plasma EBV DNA in clinical trials is underestimated, and high-level randomized clinical trials should be performed for patients with metastatic/recurrent disease.

Purpose To investigate the variability and prognostic value of nodal tumor volume (NTV) in nasopharyngeal carcinoma (NPC). Methods and materials Data on 1230 patients with newly diagnosed stage T1-4N1-3M0 NPC treated with definitive radiation therapy with or without chemotherapy at a single cancer center were reviewed. NTV was determined from dose volume histogram (DVH) data. X-tile analysis was applied to identify the optimal cut-off points for the NTV with respect to regional recurrence-free survival (RRFS). Correlations between the TNM classification system, NTV and RRFS were assessed using a Cox regression model. Cross-validation based on receiver operating characteristic (ROC) curve analysis was applied to compare the prognostic predictive validity of NTV and N categories. Results Within a median follow-up of 49.9 (range, 1.27-76.40) months, 61/1230 (5%) patients developed regional recurrence and 154 (12.5%) developed distant metastasis. NTV values of 7.2 cc and 35.7 cc were identified as the optimal cut-off points. Patients with larger NTV had poorer prognosis. Compared with the N category, NTV was better at determining RRFS for patients with NPC. Hazard ratios increased with NTV, ranging from 1.86 (95% confidence interval [95% CI], 0.92-3.78) for NTV between 7.2 cc to 35.7 cc, and 3.67 (95% CI, 1.58-8.50) for NTV > 35.7 cc. With both NTV and N category in the same Cox regression model, only NTV remained statistically significant in the RRFS of NPC. The validation results with ROC curves also revealed that, NTV was superior to N category for predicting RRFS with significantly larger area under the ROC curve. Conclusions NTV offers important prognostic value for treatment outcomes in NPC, especially regional control. Volumetric analysis of nodal involvement may assist selection of patients with poor prognosis.

Purpose To compare the outcomes of patients with ascending type (T4&N0-1) and descending type (T1-2&N3) of nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy (CCRT), neoadjuvant chemotherapy (NACT) + intensity-modulated radiotherapy (RT) or NACT + CCRT. Methods Retrospective analysis of 839 patients with ascending or descending types of NPC treated at a single institution between October 2009 to February 2012. CCRT was delivered to 236 patients, NACT + RT to 302 patients, and NACT + CCRT to 301 patients. Results The 4-year overall survival rate, distant metastasis-free survival rate, local relapse-free survival rate, nodal relapse-free survival rate, loco-regional relapse-free survival rate, and progression free survival rate were 75.2% and 73.4% (P = 0.114), 85.7% and 74.1% (P = 0.008), 88.8% and 97.1% (P = 0.013), 96.9% and 94.1% (P = 0.122), 86.9% and 91.2% (P = 0.384), 73.7% and 66.2% (P = 0.063) in ascending type and descending type. Subgroup analyses indicated that NACT + RT significantly improved distant metastasis-free survival rate and progression-free survival rate when compared with CCRT in the ascending type, and there were no significant differences between the survival curves of NACT +RT and NACT + CCRT. For descending type, there were no significant differences among the survival curves of NACT +RT, CCRT, and NACT + CCRT groups, and the survival benefit mainly came from CCRT. Conclusions Compared with NACT + CCRT or CCRT, NACT + RT may be a reasonable approach for ascending type. Although concurrent chemotherapy was effective in descending type, NACT + CCRT may be a more appropriate strategy for descending type.

Purpose The objective of this study is to assess the prognostic value of ABO blood group in nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT). Patients and methods We retrospectively reviewed the data on 1397 patients with non-metastatic, newly diagnosed NPC treated using IMRT. Patient survival between different ABO blood groups were compared using log-rank test. Cox hazards model was adopted to establish independent prognostic factors. Results In our study, the distribution of the A, B, AB and O blood groups was 26.6% (372/1397), 26.2% (366/1397), 5.2% (73/1397) and 42.0% (586/1397), respectively. The cut-off value of pre-treatment Epstein-Barr virus (EBV) DNA based on disease-free survival (DFS) was 1355 copies/ml (area under curve [AUC], 0.649; sensitivity, 0.76; specificity, 0.496) for the whole cohort. Estimated four-year DFS, overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates were 81.7%, 89.2%, 89.4% and 92.3% for blood group A; 82.1%, 89.3%, 89.0% and 92.0% for group B; 83.3%, 88.1%, 86.2% and 95.5% for group AB, 80.9%, 90.7%, 88.4% and 90.2% for group O (P > 0.05 for all rates). Multivariate analysis revealed ABO blood group was not an independent prognostic factor for DFS, OS, DMFS or LRRFS (P > 0.05 for all rates) after adjusting for plasma EBV DNA in either the whole cohort or subgroup analysis by gender. Conclusions The prognostic value of ABO blood group may be limited for patients with NPC in the era of IMRT, and no substantial correlation between ABO blood group and plasma EBV DNA was observed.

BACKGROUND:To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS:205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria. RESULTS:The median follow-up period was 37.3 months (range, 6.3-45.1 months). The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease-free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05). The most common acute and late side effects were grade 2-3 mucositis (78%) and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT), respectively. CONCLUSIONS:VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.

Purpose To report the incidence of and risk factors for mastoiditis after intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). Patients and Methods Retrospective analysis of pretreatment and follow-up magnetic resonance imaging (MRI) data for 451 patients with NPC treated with IMRT at a single institution. The diagnosis of mastoiditis was based on MRI; otomastoid opacification was rated as Grade 0 (none), 1 (mild), 2 (moderate) or 3 (severe) by radiologists blinded to clinical outcome. This study mainly focused on severe mastoiditis; patients were divided into three groups: the G0M (Grade 0 mastoiditis before treatment) group, G1-2M (Grade 1 to 2 mastoiditis before treatment) group and G3M (Grade 3 mastoiditis before treatment) group. The software SAS9.3 program was used to analyze the data. Results For the entire cohort, the incidence of Grade 3 mastoiditis was 20% before treatment and 31%, 19% and 17% at 3, 12 and 24 months after radiotherapy, respectively. In the G0M group, the incidence of severe mastoiditis was 0% before treatment and 23%, 15% and 13% at 3, 12 and 24 months after radiotherapy, respectively. Multivariate analysis revealed T category (OR=0.68, 95% CI = 0.469 to 0.984), time (OR=0.668, 95% CI = 0.59 to 0.757) and chemotherapy (OR=0.598, 95% CI = 0.343 to 0.934) were independent factors associated with severe mastoiditis in the G0M group after treatment. Conclusions Mastoiditis, as diagnosed by MRI, occurs as a progressive process that regresses and resolves over time in patients with NPC treated using IMRT.

Background Low serum albumin is predictive of poor survival in nasopharyngeal carcinoma (NPC). We evaluated the ability of the pretreatment albumin/globulin ratio (AGR) to predict long-term mortality in patients with NPC. Methods This retrospective study examined an unselected cohort of 694 patients with NPC who had documented pretreatment total serum protein and serum albumin levels (ALB). AGR was calculated as [AGR = ALB/(total serum protein - ALB)]. Survival analysis was used to evaluate the predictive value of AGR. Results Multivariate analysis demonstrated that a low pretreatment serum AGR (

The radioresistance of tumor cells remains a major cause of treatment failure in nasopharyngeal carcinoma (NPC). Recently, several reports have highlighted the importance of epigenetic changes in radiation-induced responses. Here, we investigated whether the demethylating agent 5-azacytidine (5-azaC) enhances the radiosensitivity of NPC cells. The NPC cell lines CNE2 and SUNE1 were treated with 1 μmol/L 5-azaC for 24 h before irradiation (IR); clonogenic survival was then assessed. Tumor growth was investigated in a mouse xenograft model in vivo. The apoptosis, cell cycle progression and DNA damage repair were examined using flow cytometry, immunofluorescent staining and western blotting. Promoter methylation and the expression of four genes epigenetically silenced during the development of NPC were evaluated by pyrosequencing and real-time PCR. We found that pretreatment with 5-azaC significantly decreased clonogenic survival after IR compared to IR alone; the sensitivity-enhancement ratio of 5-azaC was 1.4 and 1.2 for CNE2 and SUNE1 cells, respectively. The combined administration of 5-azaC and IR significantly inhibited tumor growth in the mouse xenograft model, and enhanced radiation-induced apoptosis in vitro compared to 5-azaC alone or IR alone. 5-AzaC also decreased promoter methylation and upregulated the expression of genes which are epigenetically silenced both in vitro and in vivo in NPC. Thus, 5-azaC enhance the radiosensitivity of both the CNE2 and SUNE1 cell lines, possibly by altering DNA methylation levels and increasing the ability of irradiated cells to undergo apoptosis. The use of 5-azaC combined with IR maybe represent an attractive strategy for the treatment of NPC.

BackgroundTo compare volumetric modulated arc therapy (VMAT) with conventional step and shoot intensity modulated radiation therapy (s-IMRT) in nasopharyngeal carcinoma (NPC) patients, and identify which T category patient gains the maximum benefit from VMAT. MethodsFifty-two patients that randomly selected from 205 patients received VMAT at a single center were retrospectively replanned with s-IMRT. For a fair comparison, the planning target volume (PTV) coverage of the 2 plans was normalized to the same level. A standard planning constraint set was used; the constraints for the organs at risk (OARs) were individually adapted. The calculated doses to the PTV and OARs were compared for s-IMRT and VMAT plans generated using the Monaco treatment planning system. ResultsVMAT and s-IMRT plans had similar PTV coverage and OAR sparing within all T categories. However, in stratified analysis, VMAT plans lead to better or similar sparing of the OARs in early T category patients; and lead to poorer sparing of the OARs in advanced T category patients (P

Background The development of intensity-modulated radiotherapy (IMRT) has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the prognostic value and classification of TNM stage system for retropharyngeal lymph node (RLN) metastasis in NPC in the IMRT era. Material and Methods We retrospectively reviewed data from 749 patients with biopsy-proven, non-metastatic NPC. All patients received IMRT as the primary treatment. Chemotherapy was administered to 86.2% (424/492) of the patients with stage III or IV disease. Results The incidence of RLN metastasis was 64.2% (481/749). Significant differences were observed in the 5-year disease-free survival (DFS; 70.6% vs. 85.4%, P