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Purpose This study was conducted to evaluate the prognostic value of treatment-related lymphopenia in patients with nasopharyngeal carcinoma (NPC). Materials and Methods A total of 413 consecutive stage II-IVb NPC patients treated with concurrent chemoradiotherapy (CCRT) were enrolled. The overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared using the log-rank test. Results A minimum (mini)-absolute lymphocyte counts (ALC) of < 390 cells/μL or ALC after 3 months of CCRT (post3m-ALC) < 705 cells/μL was significantly associated with worse outcome than mini-ALC ≥ 390 cells/μL (OS, p=0.002; PFS, p=0.005; DMFS, p=0.004) or post3m-ALC ≥ 705 cells/μL (OS, p < 0.001; PFS, p < 0.001; DMFS, p=0.001). Patients with lymphopenia (mini-ALC < 390 cells/μL and post3m-ALC < 705 cells/μL) had a worse prognosis than those without lymphopenia (mini-ALC ≥ 390 cells/μL and post3m-ALC ≥ 705 cells/μL) (OS, p < 0.001; PFS, p < 0.001; DMFS, p < 0.001). Multivariate analysis revealed that post3m-ALC was an independent prognostic factor for OS (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.12 to 2.78; p=0.015), PFS (HR, 1.86; 95% CI, 1.23 to 2.82; p=0.003), and DMFS (HR, 1.87; 95% CI, 1.13 to 3.08; p=0.014). Multivariate analysis also revealed that patients with lymphopenia had a high risk of death (HR, 3.79; 95% CI, 1.75 to 8.19; p=0.001), disease progression (HR, 2.93; 95% CI, 1.59 to 5.41; p=0.001), and distant metastasis (HR, 3.89; 95% CI, 1.67 to 9.10; p=0.002). Multivariate analysis performed with time dependent Cox regression demonstrated ALC was an independent prognostic factor for OS (HR, 0.995; 95% CI, 0.991 to 0.999; p=0.025) and PFS (HR, 0.993; 95% CI, 0.988 to 0.998; p=0.006). Conclusion Treatment-related lymphopenia was a poor prognostic factor in NPC patients. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the long-term outcome and toxicities in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated by concurrent chemoradiotherapy (CCRT) with/without adding cetuximab.Methods: A total of 62 patients treated with CCRT plus cetuximab were matched with 124 patients treated with CCRT alone by age, sex, pathological type, T category, N category, disease stage, radiotherapy (RT) technique, Epstein-Barr virus (EBV) DNA levels, and Eastern Cooperative Oncology Group (ECOG). Overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier method and log-rank test. Treatment toxicities were clarified and compared between two groups.Results: A total of 186 well-balanced stage II to IV NPC patients were retrospectively analyzed (median follow-up, 76 months). Compared to CCRT alone, adding cetuximab resulted in more grade 3 to 4 radiation mucositis (51.6% vs. 23.4%; P < 0.001). No differences were found between the CCRT + cetuximab group and the CCRT group in 5-year OS (89.7% vs. 90.7%, P = 0.386), 3-year PFS (83.9% vs. 88.7%, P = 0.115), the 3-year LRFS (95.0% vs. 96.7%, P = 0.695), and the 3-year DMFS (88.4% vs 91.9%, P = 0.068). Advanced disease stage was the independent prognostic factor predicting poorer OS and PFS.Conclusion: Adding cetuximab to CCRT did not significantly improve benefits in survival in stage II to IV NPC and exacerbated acute mucositis and acneiform rash. Further investigations are warranted. [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]

The chemokine receptor 4/chemokine ligand 12 (CXCR4/CXCL12) axis plays an important role in tumorigenesis, metastasis, and recurrence of tumors. Its single nucleotide polymorphisms (SNPs) are associated with patient survival in several types of cancer. However, the prognostic value of SNPs in nasopharyngeal carcinoma (NPC) has not been fully investigated. This retrospective study assessed the relationships between CXCR4 rs2228014 and CXCL12 rs1801157 polymorphisms and patient outcome in 222 patients newly diagnosed with NPC. The analysis found no significant correlation between the presence of both SNPs and clinicopathological factors. However, univariate analysis showed that N classification, clinical stage, and the CXCL12 rs1801157 polymorphism were significantly associated with distant metastasis-free survival (P=0.018, 0.028, and 0.013, respectively) and progression-free survival (P=0.007, 0.046, and 0.021, respectively). After adjusting clinicopathological factors, multivariate analysis identified CXCL12 rs1801157 as an independent prognostic factor for distant metastasis-free survival and progression-free survival (hazard ratio: 3.332; 95% confidence interval: 1.597-6.949; P=0.001 and hazard ratio: 2.665 95% confidence interval: 1.387-5.119; P=0.003, respectively). Our results suggest that CXCL12 rs1801157 AA genotype might serve as a potential prognostic factor in patients with NPC. [ABSTRACT FROM AUTHOR]

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]