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Background: Induction chemotherapy (IC) followed by concurrent chemo-radiotherapy (CCRT) is the current standard of care for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients. However, there is still no consensus on the optimum number of IC cycles. In this study, we aimed to assess the efficacy and toxicities of two or more cycles of IC for LA-NPC patients. Methods: Data of LA-NPC patients consecutively treated with IC followed by concurrent chemo-radiotherapy (CCRT) in our institute from 2017 to 2022 were retrospectively retrieved and analyzed. Survival outcomes of patients who received two IC cycles were compared with those who received more than two IC cycles. Univariate and multivariate Cox regression analysis were then performed to determine factors that could be independent predictors of survival. Chi-square test and Fisher's exact test were used to compare treatment associated acute toxicities between the two groups. Results: A total of 125 patients were recruited in this study. There were 89 patients who received 2 cycles (IC = 2) of IC and 36 received more than 2 cycles (IC > 2) of IC. The median follow-up time was 26 months [IQR 16–38]. The 3-year overall survival rate was not statistically significant between the two groups (95.50% vs. 86.11%, P = 0.501). Similarly, loco-regional recurrence free survival and progression free survival were not significant (97.75% vs. 97.22%, P = 0.694; and 88.76% vs. 83.33%, P = 0.129), but distant metastasis free survival was significant (88.76% vs. 86.11%, P = 0.049). Multivariate Cox regression analysis showed that IC regimen was an independent prognostic factor. Conclusions: Two cycles of IC is effective and more than two does not add any additional benefit to the survival outcomes of LA-NPC patients. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) has high incidence in Southern China and is derived from the mucosal epithelium of the nasopharynx. Accumulating evidence has revealed that peptidyl arginine deiminase 4 (PAD4) exerts carcinogenic effect on certain cancers. We designed this study to probe the specific role that PAD4 plays in NPC and its molecular mechanism. Methods: PAD4 expression in NPC cells was detected by RT-qPCR analysis. MTT, colony formation, flow cytometry, TUNEL staining, and LC3-II punctuation experiments were done to probe into the biological functions of PAD4 on NPC cellular behaviors in vitro. Subsequently, the upstream regulatory mechanism of PAD4 was investigated by luciferase reporter, RNA pull-down, and RIP assays. The impact of PAD4 on NPC tumor growth in mice was assessed by in vivo xenograft tumor assay. Results: PAD4 was upregulated in NPC cells. PAD4 knockdown suppressed proliferative ability and promoted apoptosis and autophagy in NPC cells. Additionally, PAD4 expression was negatively regulated by microRNA 3164 (miR-3164). LINC00324 positively upregulated PAD4 expression by interacting with miR-3164 and recruiting HuR protein. The LINC00324/miR-3164/PAD4 axis modulated the PI3K/AKT pathway in NPC cells. Moreover, PAD4 upregulation countervailed the influences of LINC00324 deficiency on NPC cell proliferation, apoptosis, and autophagy and on NPC tumor growth in mice. Conclusion: LINC00324 promoted NPC malignancy by upregulation of PAD4 to activate the PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Background and purpose: Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) has been established as standard of care for locoregionally advanced nasopharyngeal carcinoma (LANPC). No direct comparison between different IC regimens has been performed. We conducted Bayesian network meta-analysis to evaluate the efficacy and safety of IC regimens in LANPC. Materials and methods: We systematically searched studies comparing different regimens of IC plus CCRT versus CCRT alone for LANPC. Pairwise meta-analysis and Bayesian network meta-analysis were conducted using Review Manger, Stata and R software. Results: Eight eligible studies with a total of 2382 patients were involved. Compared with CCRT alone, IC + CCRT significantly improved PFS (HR = 0.68 [95% CI 0.59–0.79]) and OS (HR = 0.72 [95% CI 0.61–0.86]) in conventional meta-analysis. In Bayesian network meta-analysis, GP (gemcitabine and cisplatin) had advantage in prolonging PFS, OS and DMFS. GP had adverse but manageable impacts on hemoglobin and platelet. Meanwhile, treatment compliance of GP was higher than that of other regimens. Conclusion: Based on existing evidences, GP could likely to be recommended as an optimal IC regimen for LANPC. [ABSTRACT FROM AUTHOR]

Radiotherapy-related caries is a complication of radiotherapy for nasopharyngeal carcinoma; however, factors influencing the occurrence, accurate prediction of onset, and protective factors of radiotherapy-related caries remain unclear. This study analyzed risk factors, disease predictors, and protective factors for radiotherapy-related caries in nasopharyngeal carcinoma. This prospective study included 138 nasopharyngeal carcinoma patients receiving radical radiotherapy at our hospital during June 2012–December 2016 and were followed up for dental caries. Patients' clinical data on radiotherapy were collected, dynamic monitoring was performed to assess changes in oral pH values, and a questionnaire survey was administered to collect patients' lifestyle habits. Time-dependent cox regression trees, event-free Kaplan–Meier curve, Mann–Whitely U test were used to analysis the results. The median follow-up time was 30 (12–60) months. Radiotherapy-related caries occurred in 28 cases (20.3%). Univariate analyses showed that radiotherapy-related caries was associated with patient's age, oral saliva pH value, green tea consumption, and radiation dose to sublingual glands, but not with the radiation dose to the parotid and submandibular glands. Multivariate analysis showed that oral saliva pH value [hazard ratio (HR) = 0.390, 95% confidence interval = 0.204–0.746] was an independent prognostic factor for radiotherapy-related caries. Patients with oral saliva pH values ≤ 5.3 in the 9th month after radiotherapy represented a significantly higher risks for radiotherapy-related caries (p < 0.001). Green tea consumption was associated with the occurrence of radiotherapy-related caries, and oral saliva pH values could predict the occurrence of radiotherapy-related caries. Limiting radiation doses to sublingual glands can reduce the occurrence of radiotherapy-related caries. [ABSTRACT FROM AUTHOR]

Background: Radiation‐induced mucositis (RIOM) is a common radiotherapy toxicity. We aimed to evaluate the relationship of serum vitamin status with RIOM among nasopharyngeal carcinoma (NPC) patients who underwent radiotherapy. Methods: NPC patients who underwent concurrent chemoradiotherapy with available pretreatment serum vitamin values were included. Serum vitamin levels and clinical characteristics were collected. Logistic regression analysis and receiver operating characteristic curves were conducted to explore the potential risk factors and corresponding cut‐off values for severe RIOM. Results: Two hundred and forty NPC patients were enrolled. Multivariate regression analysis showed that mean oral cavity radiation dose (OR = 2.042; 95% CI = 1.585‐2.630; P <.001), weekly concurrent chemotherapy (OR = 3.898; 95% CI = 1.085‐14.004; P =.037), lower serum level of vitamin B2 (OR = 0.951; 95% CI = 0.924‐0.978; P <.001), and vitamin C (OR = 0.455; 95% CI = 0.346‐0.598; P <.001) were independent risk factors for developing severe RIOM. Conclusions: The findings of this study revealed that serum vitamin status could predict the severity of RIOM, providing a theoretical basis for the prevention and treatment of RIOM. [ABSTRACT FROM AUTHOR]

Upward (local growth and invasion of the base of skull), downward (distant metastasis) and mixed progressing types of nasopharyngeal carcinoma (NPC) have been identified and are distinctly different with respect to clinical symptoms, therapeutic strategies and prognosis. The present study aimed to identify the genetic difference and collagen expression levels in the upward and downward progressing types of NPC. Whole exon sequencing (WES) was used to detect genes differentially mutated between the upward and downward progressing types of NPC. Collagen deposition in the upward and downward progressing types of NPC was determined using Masson trichromatic staining, while the protein expression level of COL4A3 was detected using immunohistochemistry. Survival analysis was also performed using the Kaplan-Meier Plotter database to examine the role of COL4A3 expression level in the prognosis of head and neck squamous cell carcinoma. Knockdown of COL4A3 was performed using short interfering (si)RNA-COL4A3 in a 5-8F NPC cell line. Reverse transcription-quantitative PCR and western blot analyses were utilized to analyze the mRNA and protein expression levels of COL4A3, respectively. The roles of COL4A3 in the migration and invasion of the 5-8F cell line were examined using wound-healing Transwell and Matrigel assays, respectively. A total of 21 genes were differentially mutated between the upward and downward progressing types of NPC. The COL4A3 was investigated further, as it was found to be associated with extracellular matrix deposition and cancer metastasis. The COL4A3 gene was markedly downregulated in the downward progressing type compared with that in the upward progressing type (2.161±1.306 vs. 5.077±3.619; P<0.05). In addition, the deposition of collagen in the downward progressing type was also significantly decreased compared with that in the upward progressing type (5.63±6.83 vs. 10.94±9.60; P<0.05). Kaplan-Meier analysis indicated that high expression level of COL4A3 was positively associated with a favorable prognosis of head and neck squamous cell carcinoma (HR, 0.69; 95% CI, 0.49- 0.97; P=0.031). To confirm the role of COL4A3, the expression level of COL4A3 was knocked down using siRNA in the 5-8F cell line and the results showed that the invasion and migration was significantly increased when the expression of COL4A3 was inhibited (P<0.0001). In conclusion, the gene mutation patterns were significantly different between the upward and downward progressing types of NPC. In addition, the expression level of the COL4A3 gene was decreased in the downward progressing type, which might promote NPC metastasis through the downregulation of extracellular collagen expression. [ABSTRACT FROM AUTHOR]