OBJECTIVE: To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R. METHODS: Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 µ g/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label. RESULTS: The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 µ g/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened (P<0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results. CONCLUSIONS SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.
Animals ; Humans ; Nasopharyngeal Carcinoma/genetics* ; Epithelial-Mesenchymal Transition ; Zebrafish ; Cell Proliferation ; Cell Line, Tumor ; Nasopharyngeal Neoplasms/radiotherapy* ; Cell Movement ; Gene Expression Regulation, Neoplastic

To investigate the γ pass rate limit of plan verification equipment for volumetric modulated arc therapy (VMAT) plan verification and its sensitivity on the opening and closing errors of multi-leaf collimator (MLC), 50 cases of nasopharyngeal carcinoma VMAT plan with clockwise and counterclockwise full arcs were randomly selected. Eight kinds of MLC opening and closing errors were introduced in 10 cases of them, and 80 plans with errors were generated. Firstly, the plan verification was conducted in the form of field-by-field measurement and true composite measurement. The γ analysis with the criteria of 3% dose difference, distance to agreement of 2 mm, 10% dose threshold, and absolute dose global normalized conditions were performed for these fields. Then gradient analysis was used to investigate the sensitivity of field-by-field measurement and true composite measurement on MLC opening and closing errors, and the receiver operating characteristic curve (ROC) was used to investigate the optimal threshold of γ pass rate for identifying errors. Tolerance limits and action limits for γ pass rates were calculated using statistical process control (SPC) method for another 40 cases. The error identification ability using the tolerance limit calculated by SPC method and the universal tolerance limit (95%) were compared with using the optimal threshold of ROC. The results show that for the true composite measurement, the clockwise arc and the counterclockwise arc, the descent gradients of the γ passing rate with per millimeter MLC opening error are 10.61%, 7.62% and 6.66%, respectively, and the descent gradients with per millimeter MLC closing error are 9.75%, 7.36% and 6.37%, respectively. The optimal thresholds obtained by the ROC method are 99.35%, 97.95% and 98.25%, respectively, and the tolerance limits obtained by the SPC method are 98.98%, 97.74% and 98.62%, respectively. The tolerance limit calculated by SPC method is close to the optimal threshold of ROC, both of which could identify all errors of ±2 mm, while the universal tolerance limit can only partially identify them, indicating that the universal tolerance limit is not sensitive on some large errors. Therefore, considering the factors such as ease of use and accuracy, it is suggested to use the true composite measurement in clinical practice, and to formulate tolerance limits and action limits suitable for the actual process of the institution based on the SPC method. In conclusion, it is expected that the results of this study can provide some references for institutions to optimize the radiotherapy plan verification process, set appropriate pass rate limit, and promote the standardization of plan verification.
Humans ; Radiotherapy, Intensity-Modulated ; Immune Tolerance ; Nasopharyngeal Carcinoma ; ROC Curve ; Nasopharyngeal Neoplasms/radiotherapy*

Objective: To study the effect of circ-WHSC1 on the growth, metastasis and radiosensitivity of nasopharyngeal carcinoma cells and its molecular mechanism. Methods: Cancerous tissues and adjacent tissues were collected from 23 patients with nasopharyngeal carcinoma, and real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the expression levels of circ-WHSC1, miR-338-3p, and ELAVL1 mRNA. Western blot was used to detect the expression of ELAVL1 protein. Nasopharyngeal carcinoma cells 5-8F and SUNE1 were divided into si-NC group, si-circ-WHSC1 group, pCD5-ciR group, circ-WHSC1 group, anti-miR-NC group, anti-miR-338-3p group, miR-NC group, miR-338-3p group, si-circ-WHSC1+ anti-miR-NC group, si-circ-WHSC1+ anti-miR-338-3p group, miR-338-3p+ pcDNA group, miR-338-3p+ ELAVL1 group. Tetramethylazolium salt colorimetric method (MTT) was used to detect cell viability. Clone formation test was used to detect cell clone formation and cell radiosensitivity. Flow cytometry was used to detect cell apoptosis. Transwell was used to detect cell migration and invasion. Dual luciferase assay was used to detect the targeting relationship between circ-WHSC1 and miR-338-3p, miR-338-3p and ELAVL1. The SUNE1 cells stably transfected with sh-circ-WHSC1 were injected into nude mice and irradiated with radiation, and then the tumor volume and weight of mice were detected. Results: The expressions of circ-WHSC1 (1.57±0.94 vs 3.78±1.18, 1.00±0.10 vs 1.64±0.14/2.00±0.21/2.81±0.26/3.36±0.34) and ELAVL1 (1.28±0.74 vs 3.36±0.77, 1.00±0.08 vs 2.51±0.19/3.27±0.27) in nasopharyngeal carcinoma tissues and cells were increased, and the expression of miR-338-3p (3.13±0.96 vs 1.37±0.98, 1.00±0.08 vs 0.48±0.08/0.38±0.07) was decreased (P<0.05). After knockdown of circ-WHSC1, the activity of nasopharyngeal carcinoma cells was decreased [(100.00±8.00)% vs (51.33±8.62)%, (100.00±10.10)% vs (41.02±7.31)%], the number of clone-forming cells was decreased (101.00±8.54 vs 50.33±8.02, 114.00±14.10 vs 42.33±10.01), the rate of apoptosis was increased [(5.37±1.20)% vs (18.3±1.01)%, (6.5±1.18)% vs (22.43±1.40)%], and the numbers of migration (136.00±13.00 vs 72.33±9.50, 154.00±14.10 vs 62.67±11.50) and invasion (113.67±11.59 vs 60.67±9.07, 124.33±15.57 vs 50.33±9.01) were decreased; after different doses of radiation, the cell survival score was decreased (0.23±0.04 vs 0.06±0.01, 0.32±0.07 vs 0.05±0.02) (P<0.05). Circ-WHSC1 targeted and negatively regulated miR-338-3p. Inhibition of miR-338-3p affected the effect of knockdown of circ-WHSC1 on the proliferation, apoptosis, migration, invasion and radiosensitivity of nasopharyngeal carcinoma cells. MiR-338-3p targeted and negatively regulated ELAVL1; ELAVL1 overexpression affected the effects of miR-338-3p on the proliferation, apoptosis, migration, invasion and radiosensitivity of nasopharyngeal carcinoma cells. After the cells stably transfected with sh-circ-WHSC1 were injected into nude mice, the tumor volume [(884.67±95.63)mm(3) vs (487.33±76.51)mm(3)] and weight [(899.01±88.54)mg vs (558.67±75.04) mg] of the nude mice were reduced; after further irradiation, the tumor volume [(395.00±73.50)mm(3) vs 243.13±42.51)mm(3)] and weight[ (452.33±67.30)mg vs (211.09±57.51)mg] of the nude mice were reduced (P<0.05). Circ-WHSC1 regulated the expression of ELAVL1 by targeting miR-382. Conclusion: Knockdown of circ-WHSC1 can inhibit the growth and metastasis of nasopharyngeal carcinoma cells by targeting miR-338-3p/ELAVL1 axis, and enhances the radiosensitivity of nasopharyngeal carcinoma cells.
Mice ; Animals ; Nasopharyngeal Carcinoma/radiotherapy* ; Mice, Nude ; MicroRNAs/genetics* ; Antagomirs ; Cell Line, Tumor ; Radiation Tolerance/genetics* ; Nasopharyngeal Neoplasms/pathology* ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic

Objective: To develop a designing software of digital oral positioning stent for radiotherapy of head and neck, and to compare its clinical effect with traditional oral positioning stents made by lost wax process. Methods: Thirty patients with nasopharyngeal cancer who received oral examination before radiotherapy in the prosthodontics department from July to December, 2021, were selected and divided into three groups according to the patients' wishes, 10 per group: one group without radiotherapy oral positioning stents, one group with traditional oral positioning stents (traditional stents group), and the third group with digital oral positioning stents (digital stents group). Patients' ages range from 20 years old to 71 years old. There were 15 males and 15 females involved in this study. The manufacturing time and comfort of the two positioning stents were evaluated, and the radiation doses of the radiotherapy target areas and surrounding healthy tissues were statistically analyzed at the end of radiotherapy. Results: The manufacturing time of digital stents group [(209±7) min] was much less than that of traditional stents group [(490±10) min] (t=69.85, P<0.001). The comfort of patients' wearing of digital stents [first wearing: 5 (3, 6) score; at the end of radiotherapy: 4 (3, 5) score] was better than that of traditional ones [first wearing: 7 (3, 7) score; at the end of radiotherapy: 7 (3, 7) score] (U=22.00, P=0.033; U=20.50, P=0.023). There was no significant differences in the target radiation doses among the three groups, and the radiation doses of tongue [traditional stents group: (36.74±5.45) Gy; digital stents group: (35.96±4.98) Gy] and mandible [traditional stents group: (35.46±4.19) Gy; digital stents group: (35.34±3.98) Gy] were significantly lower in the patients wearing oral positioning stents than in the patients without oral positioning stents [tongue: (41.49±4.46) Gy; madible: (39.32±3.52) Gy] (P<0.05). Conclusions: Oral positioning stents for nasopharyngeal carcinoma radiotherapy could greatly reduce the exposure doses of tongue and madible of patients. Digital oral positioning stents designed and manufactured by independently developed software had higher production efficiency than the traditional method, and patients' evaluation of comfort was better.
Humans ; Male ; Female ; Young Adult ; Adult ; Nasopharyngeal Neoplasms/radiotherapy* ; Head and Neck Neoplasms/radiotherapy* ; Tongue ; Stents ; Neck ; Radiotherapy Dosage

OBJECTIVE: To investigate the accuracy of automatic segmentation of organs at risk (OARs) in radiotherapy for nasopharyngeal carcinoma (NPC). METHODS: The CT image data of 147 NPC patients with manual segmentation of the OARs were randomized into the training set (115 cases), validation set (12 cases), and the test set (20 cases). An improved network based on three-dimensional (3D) Unet was established (named as AUnet) and its efficiency was improved through end-to-end training. Organ size was introduced as a priori knowledge to improve the performance of the model in convolution kernel size design, which enabled the network to better extract the features of different organs of different sizes. The adaptive histogram equalization algorithm was used to preprocess the input CT images to facilitate contour recognition. The similarity evaluation indexes, including Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD), were calculated to verify the validity of segmentation. RESULTS: DSC and HD of the test dataset were 0.86±0.02 and 4.0±2.0 mm, respectively. No significant difference was found between the results of AUnet and manual segmentation of the OARs ( CONCLUSIONS AUnet, an improved deep learning neural network, is capable of automatic segmentation of the OARs in radiotherapy for NPC based on CT images, and for most organs, the results are comparable to those of manual segmentation.
Databases, Factual ; Humans ; Image Processing, Computer-Assisted ; Nasopharyngeal Carcinoma/radiotherapy* ; Nasopharyngeal Neoplasms/radiotherapy* ; Organs at Risk ; Tomography, X-Ray Computed

PURPOSE: The purpose of this study was to investigate the effect of hospital case volume on clinical outcomes in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Data on 1,073 patients with cT1-4N0-3M0 NPC were collected from a multi-institutional retrospective database (KROG 11-06). All patients received definitive radiotherapy (RT) either with three-dimensional-conformal RT (3D-CRT) (n=576) or intensity-modulated RT (IMRT) (n=497). The patients were divided into two groups treated at high volume institution (HVI) (n=750) and low volume institution (LVI) (n=323), defined as patient volume ≥ 10 (median, 13; range, 10 to 18) and < 10 patients per year (median, 3; range, 2 to 6), respectively. Endpoints were overall survival (OS) and loco-regional progression-free survival (LRPFS). RESULTS: At a median follow-up of 56.7 months, the outcomes were significantly better in those treated at HVI than at LVI. For the 614 patients of propensity score-matched cohort, 5-year OS and LRPFS were consistently higher in the HVI group than in the LVI group (OS: 78.4% vs. 62.7%, p < 0.001; LRPFS: 86.2% vs. 65.8%, p < 0.001, respectively). According to RT modality, significant difference in 5-year OS was observed in patients receiving 3D-CRT (78.7% for HVI vs. 58.9% for LVI, p < 0.001) and not in those receiving IMRT (77.3% for HVI vs. 75.5% for LVI, p=0.170). CONCLUSION: A significant relationship was observed between HVI and LVI for the clinical outcomes of patients with NPC. However, the difference in outcome becomes insignificant in the IMRT era, probably due to the standardization of practice by education.
Cohort Studies ; Disease-Free Survival ; Education ; Follow-Up Studies ; Humans ; Nasopharyngeal Neoplasms ; Radiotherapy ; Radiotherapy, Intensity-Modulated ; Retrospective Studies* ; Treatment Outcome

To explore the correlation of quality of life with self-care efficacy and social support in patients with nasopharyngeal carcinoma after radiotherapy.
 Methods: A total of 179 patients with nasopharyngeal carcinoma at 3 months after radiotherapy were surveyed using self-designed general information questionnaire, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30 V3.0), Chinese-version of Strategies Used by People to Promote Health (C-SUPPH), and Perceived Social Support Scale (PSSS).
 Results: The score of cognitive function was the highest, while the score of social function was the lowest. The score of related symptoms was 22.21±10.24, the overall score for quality of life was 52.46±17.96, the score of self-care efficacy was 62.14±14.50, and the score of social support was 56.03±7.63. Self-care efficacy of patients with nasopharyngeal cancer after radiotherapy was positively correlated with 5 functional areas of quality of life and overall quality of life, and negatively correlated with relevant symptoms (P<0.01). Social support was positively correlated with physical function, social function and overall quality of life (P<0.01), and negatively correlated with relevant symptoms (P<0.05). Multiple regression analysis showed that self-care efficacy could predict 5 functional areas of life quality, relevant symptoms, overall quality of life and social support predicted social function in quality of life.
 Conclusion: Self-care efficacy and social support for patients with nasopharyngeal cancer after radiotherapy can affect their quality of life. Nursing staff should pay attention to improving the self-care efficacy of patients, guide them to actively seek or obtain social support, and in turn to improve their quality of life.
Humans ; Nasopharyngeal Carcinoma ; radiotherapy ; Nasopharyngeal Neoplasms ; radiotherapy ; Quality of Life ; Self Care ; Social Support

PURPOSE: This study aimed to report the clinical outcomes following selective neck irradiation (SNI) with lower elective radiation therapy (RT) dose in treating nasopharyngeal cancer (NPC) patients. MATERIALS AND METHODS: A total of 347 NPC patients received definitive RT according to our SNI policy and were retrospectively analyzed. The clinical target volumes (CTVs) were subdivided into CTV at high risk (CTV-HR) and CTV at low risk (CTV-LR). The typical doses to gross tumor volume (GTV), CTV-HR, and CTV-LR were 68.4-70.0 Gy, 54.0-60.0 Gy, and 36.0 Gy. RESULTS: With the median follow-up of 68.1 months (range, 2.3 to 197.1 months), the 5-year rates of loco-regional control and progression-free survival in all the patients were 85.0% and 70.8%, respectively. Thirty patients developed regional failure and the regional control rates at 3 and 5 years were 92.6% and 91.4%, respectively. The sites of regional failure in relation to the target volume were exclusively inside GTV/CTV-HR in 20, inside and outside GTV/CTVHR in three, and exclusively outside GTV/CTV-HR in seven, which were 5.7%, 0.9%, and 2.0% of total patients, respectively. CONCLUSION: The clinical outcomes by the current SNI policy were feasible and comparable to those following classic elective nodal irradiation policy.
Disease-Free Survival ; Follow-Up Studies ; Humans ; Lymphatic Irradiation ; Nasopharyngeal Neoplasms ; Nasopharynx ; Neck ; Radiotherapy ; Retrospective Studies ; Tumor Burden

PURPOSE: We evaluated prognostic value of the 8th edition of the American Joint Committee on Cancer/International Union for Cancer Control (AJCC/UICC) staging system for nasopharyngeal cancer and investigated whether tumor volume/metabolic information refined prognostication of anatomy based staging system. MATERIALS AND METHODS: One hundred thirty-three patients with nasopharyngeal cancer who were staged with magnetic resonance imaging (MRI) and treated with intensity-modulated radiotherapy (IMRT) between 2004 and 2013 were reviewed. Multivariate analyses were performed to evaluate prognostic value of the 8th edition of the AJCC/UICC staging system and other factors including gross tumor volume and maximum standardized uptake value of primary tumor (GTV-T and SUV-T). RESULTS: Median follow-up period was 63 months. In multivariate analysis for overall survival (OS), stage group (stage I-II vs. III-IVA) was the only significant prognostic factor. However, 5-year OS rates were not significantly different between stage I and II (100% vs. 96.2%), and between stage III and IVA (80.1% vs. 71.7%). Although SUV-T and GTV-T were not significant prognostic factors in multivariate analysis, those improved prognostication of stage group. The 5-year OS rates were significantly different between stage I-II, III-IV (SUV-T ≤ 16), and III-IV (SUV-T > 16) (97.2% vs. 78% vs. 53.8%), and between stage I, II-IV (GTV-T ≤ 33 mL), and II-IV (GTV-T > 33 mL) (100% vs. 87.3% vs. 66.7%). CONCLUSION: Current anatomy based staging system has limitations on prognostication for nasopharyngeal cancer despite the most accurate assessment of tumor extent by MRI. Tumor volume/metabolic information seem to improve prognostication of current anatomy based staging system, and further studies are needed to confirm its clinical significance.
Follow-Up Studies ; Humans ; Joints ; Magnetic Resonance Imaging ; Multivariate Analysis ; Nasopharyngeal Neoplasms ; Neoplasm Staging ; Prognosis ; Radiotherapy, Intensity-Modulated ; Tumor Burden

PURPOSE: To investigate the predictive role of maximum standardized uptake value (SUVmax) of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in nasopharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Between October 2006 and April 2016, 53 patients were treated with IMRT in two institutions and their PET/CT at the time of diagnosis was reviewed. The SUVmax of their nasopharyngeal lesions and metastatic lymph nodes (LN) was recorded. IMRT was delivered using helical tomotherapy. All patients except for one were treated with concurrent chemoradiation therapy (CCRT). Correlations between SUVmax and patients’ survival and recurrence were analyzed. RESULTS: At a median follow-up time of 31.5 months (range, 3.4 to 98.7 months), the 3-year overall survival (OS) and disease-free survival (DFS) rates were 83.2% and 77.5%, respectively. In univariate analysis, patients with a higher nodal pre-treatment SUVmax (≥ 13.4) demonstrated significantly lower 3-year OS (93.1% vs. 55.5%; p = 0.003), DFS (92.7% vs. 38.5%; p < 0.001), locoregional recurrence-free survival (100% vs. 50.5%; p < 0.001), and distant metastasis-free survival (100% vs. 69.2%; p = 0.004), respectively. In multivariate analysis, high pre-treatment nodal SUVmax (≥ 13.4) was a negative prognostic factor for OS (hazard ratio [HR], 7.799; 95% confidence interval [CI], 1.506–40.397; p = 0.014) and DFS (HR, 9.392; 95% CI, 1.989–44.339; p = 0.005). CONCLUSIONS: High pre-treatment nodal SUVmax was an independent prognosticator of survival and disease progression in nasopharyngeal carcinoma patients treated with IMRT in our cohort. Therefore, nodal SUVmax may provide important information for identifying patients who require more aggressive treatment.
Cohort Studies ; Diagnosis ; Disease Progression ; Disease-Free Survival ; Electrons ; Fluorodeoxyglucose F18* ; Follow-Up Studies ; Humans ; Lymph Nodes ; Multivariate Analysis ; Nasopharyngeal Neoplasms ; Positron-Emission Tomography and Computed Tomography* ; Radiotherapy, Intensity-Modulated* ; Recurrence