Search

Background: This prospective study was conducted to evaluate inter- and intra-fraction errors in nasopharyngeal carcinoma (NPC) patients undergoing volumetric modulated arc therapy (VMAT) using cone-beam computed tomography (CBCT) and to thus obtain planning target volume (PTV) margins to effectively guide treatment in the future. Methods: Fifteen NPC patients scheduled to undergo VMAT were prospectively enrolled in the study. For each patient, three CBCT scans were obtained; one after daily conventional positioning, one after online correction with 2 mm tolerance and one after 1 week of VMAT delivery. The scans were registered to the planning CT to determine the inter- and intra-fraction errors. Patient positioning errors were analyzed for time trends over the course of radiotherapy. PTV margins were calculated from the systematic (∑) and random (σ) errors. Results: The average absolute values of the pre-correction, post-correction and intra-fraction errors (in order) were 1.1, 0.6 and 0.4 mm in the medial-lateral (ML) direction, 1.2, 0.7 and 0.5 mm in the superior-inferior (SI) direction and 1.1, 0.7 and 0.5 mm in the anterior-posterior (AP) direction. The corresponding ∑ were 1.0-1.4 mm, 0.4-0.5 mm and 0.2-0.4 mm, while the corresponding s were 0.7-0.8 mm, 0.6-0.7 mm and 0.5-0.6 mm. With time, gradual increases in both the inter- and intra-fraction three-dimensional displacements were observed (P = 0.019 and P = 0.044, respectively). The total PTV margins accounting for pre-correction and intra-fraction errors were 3.4-4.1 mm and those accounting for post-correction and intra-fraction errors were 1.7-2.2 mm. Conclusions: CBCT is an effective modality to evaluate and improve the accuracy of VMAT in NPC patients. Inter- and intra-fraction three-dimensional displacements increased as a function of time during the course of radiotherapy. In our institution, we recommend a PTV margin of 5 mm for NPC patients undergoing VMAT without CBCT and 3 mm for those treated with rigorous daily CBCT scans. [ABSTRACT FROM AUTHOR]

Background: To evaluate the incidence of neck muscle spasm in nasopharyngeal carcinoma (NPC) patients that received intensity-modulated radiotherapy (IMRT), and to analyse the patient- and treatment-related risk factors associated with neck muscle spasm.Methods: A sample of 152 IMRT-treated, biopsy-proven, nondisseminated NPC patients were retrospectively analysed. All had documented IMRT treatment plans and had returned for follow-up review at 4 years post-radiotherapy. Spasm of the sternocleidomastoid (SCM) muscle was graded from 0 to 3 (absent to severe) and this grade served as the clinical endpoint. Risk factors were identified using logistic regression analysis.Results: Within 4 years of radiotherapy, neck muscle spasm developed in 23.68% of the patients; Grades 0, 1, 2 and 3 were respectively assigned to 83.55, 7.57, 6.58 and 2.30% of assessed SCMs. Multivariate analysis indicated that gender, N stage, V60 (percentage of SCM volume that received >60 Gy) were independent prognostic variables, and that the optimal threshold for using V60 to predict neck muscle spasm was 61.92% (sensitivity = 0.900, specificity = 0.953).Conclusions: Gender, N stage and V60 were independent predictive factors for post-radiotherapy neck muscle spasm, and a V60 of ≤61.92% in the SCM was relatively safe. [ABSTRACT FROM AUTHOR]

Background: Epigenetic abnormalities play important roles in nasopharyngeal cancer (NPC), however, the epigenetic changes associated with abnormal cell proliferation remain unclear. Methods: We detected epigenetic change of ZNF671 in NPC tissues and cell lines by bisulfite pyrosequencing. We evaluated zinc finger protein 671 (ZNF671) expression in NPC cell lines and clinical tissues using real-time PCR and western blotting. Then, we established NPC cell lines that stably overexpressed ZNF671 and knocked down ZNF671 expression to explore its function in NPC in vitro and in vivo. Additionally, we investigated the potential mechanism of ZNF671 by identifying the mitotic spindle and G2/M checkpoint pathways pathway downstream genes using gene set enrichment analysis, flow cytometry and western blotting. Results: ZNF671 was hypermethylated in NPC tissues and cell lines. The mRNA and protein expression of ZNF671 was down-regulated in NPC tissues and cell lines and the mRNA expression could be upregulated after the demethylation agent 5-aza-2'-deoxycytidine treatment. Overexpression of ZNF671 suppressed NPC cell proliferation and colony formation in vitro; silencing ZNF671 using a siRNA had the opposite effects. Additionally, overexpression of ZNF671 reduced the tumorigenicity of NPC cells in xenograft model in vivo. The mechanism study determined that overexpressing ZNF671 induced S phase arrest in NPC cells by upregulating p21 and downregulating cyclin D1 and c-myc. Conclusions: Epigenetic mediated zinc finger protein 671 downregulation promotes cell proliferation and enhances tumorigenicity by inhibiting cell cycle arrest in NPC, which may represent a novel potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Metastasis remains the major cause of death in nasopharyngeal carcinoma (NPC). Yippee-like 3 (YPEL3) plays an important role in tumorigenesis. However, its function and mechanism in NPC has not been systematically explored. Methods: We evaluated YPEL3 expression in NPC cell lines and tissues using real-time PCR and western blotting. Then, we established NPC cell lines that stably overexpressed YPEL3 and knocked down YPEL3 expression to explore its function in NPC in vitro and in vivo. Additionally, we investigated the potential mechanism of YPEL3 action by identifying the Wnt/β-catenin signaling pathway downstream genes using western blotting. Results: YPEL3 was downregulated in NPC cell lines and tissue samples. Ectopic expression of YPEL3 inhibited NPC cell migration and invasion in vitro; while silencing of YPEL3 promoted NPC cell migration and invasion. Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial-mesenchymal transition (EMT) and that silencing it enhanced EMT. Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo. The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/β-catenin signaling pathway downstream genes and the nuclear translocation of β-catenin. Conclusions: YPEL3 suppresses NPC EMT and metastasis by suppressing the Wnt/β-catenin signaling pathway, which would help better understanding the molecular mechanisms of NPC metastasis and provide novel therapeutic targets for NPC treatment. [ABSTRACT FROM AUTHOR]

Background: In the era of intensity-modulated radiotherapy (IMRT), the efficacy of additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) is currently being investigated in ongoing trials. Overall survival (OS) is the gold standard endpoint in NPC trials. We performed this analysis to identify surrogate endpoints for OS, which could shorten follow-up duration and speed up assessment of treatment effects.Methods: We retrospectively analysed 208 matched-pair patients with locoregionally advanced NPC receiving NACT+CCRT or CCRT. Progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) and locoregional failure-free survival (LR-FFS) at 2 and 3 years were assessed as surrogates for 5-year OS according to Prentice's criteria. The strength of the associations were assessed using Spearman's rank correlation coefficient.Results: No significant differences were observed between treatment arms for any surrogate endpoint at 2 years, which rejected Prentice's second criterion. In contrast, 3-year LR-FFS, PFS, FFS and D-FFS were consistent with all four of Prentice's criteria; the rank correlation coefficient (0.730) between 3-year PFS and 5-year OS was highest.Conclusions: 3-year PFS, FFS and D-FFS could be valid surrogate endpoints for 5-year OS; 3-year PFS may be the most accurate. [ABSTRACT FROM AUTHOR]

Background: To evaluate the influence of the progonistic nutritional index (PNI) and weight loss on metastasis and long-term mortality in nasopharyngeal carcinoma (NPC).Methods: We retrospectively reviewed 694 newly diagnosed patients with non-disseminated, biopsy-proven NPC. Survival analysis was used to evaluate the predictive value of PNI and weight loss.Results: Multivariate analysis demonstrated that a low pre-therapy PNI (< 55.0) was an independent predictor of poor overall survival (OS) (P = 0.012), distant metastasis-free survival (DMFS) (P = 0.011) and progression-free survival (P = 0.012). High weight loss (HWL, weight loss during treatment ≥10 %) was an independent predictor of poor OS (P = 0.001) and DMFS (P = 0.014). Advanced stage disease, female gender, chemotherapy, high white blood cell count, high serum globulin concentration and pre-therapy body-mass index were predictors of HWL.Conclusion: Pre-therapy PNI and weight loss have significant predictive value for metastasis and mortality in patients with NPC. [ABSTRACT FROM AUTHOR]

Background: To compare the survival outcomes and acute toxicities of concurrent chemoradiotherapy (CCRT), induction chemotherapy (IC) plus radiotherapy (RT), and IC plus CCRT in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated using intensity-modulated radiotherapy (IMRT).Methods: Patients with stage III-IVB NPC who were treated with IMRT between 2009 and 2012 at a single institution were retrospectively reviewed. The induction regimens included PF (cisplatin and fluorouracil) and TP (docetaxel and cisplatin) every 3 weeks for 2-3 cycles; the concurrent regimen was cisplatin every three weeks for 2-3 cycles. A propensity score matching method was used to match patients from each group in a 1:1:1 ratio.Results: In total, 147 eligible patients were propensity-matched, with 49 patients in each treatment group. The median follow-up duration was 38.5 months (range, 4.5 - 56 months). The 3-year disease-free survival, overall survival, distant metastasis-free survival, and locoregional relapse-free survival rates were 82.1%, 92.8%, 87%, and 90.4% in the CCRT group; 86.3%, 91.0%, 91.6%, and 94.4% in the IC plus RT group; and 87.8%, 95.8%, 93.8%, and 93.9% in the IC plus CCRT group, respectively. No statistically significant survival differences were observed between the three treatment groups in either univariate or multivariate analyses. The incidence of grade 3-4 acute toxicities was similar among groups.Conclusions: This study suggests that CCRT, IC plus RT, and IC plus CCRT are similarly efficacious treatment strategies for patients with locoregionally advanced NPC treated using IMRT; however, long-term, large-scale randomized trials are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Background MiRNAs play important roles in diverse biological processes including tumorigenesis. However, little is known about the function and mechanism of miR-451 in nasopharyngeal carcinoma (NPC). Methods Quantitative RT-PCR was used to quantify miR-451 expression in NPC cell lines and clinical tissues. Kaplan-Meier curves were used to estimate the association between miR-451 expression and survival. The MTT, colony formation, Transwell migration and invasion assays, and a xenograft model were performed. A miR-451 target was confirmed using luciferase reporter assays, quantitative RT-PCR, and Western blotting. Results MiR-451 was significantly downregulated in NPC cell lines and clinical tissues (P < 0.01). Patients with low expression of miR-451 had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P = 0.01) and disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) than patients with high expression. MiR-451 was an independent prognostic factor in NPC in multivariate Cox regression analysis. Ectopic expression of miR-451 suppressed cell viability, colony formation, and cell migration and invasion in vitro, and inhibited xenograft tumor growth in vivo. MIF was verified as a direct target of miR-451, and MIF regulated NPC cell growth and invasion. Conclusions The newly identified miR-451/MIF pathway provides insight into NPC initiation and progression, and may represent a novel therapeutic target. [ABSTRACT FROM AUTHOR]