Prediction of anatomical images during radiotherapy of nasopharyngeal carcinoma with deep learning method / 中华放射肿瘤学杂志

Objective:To develop a deep learning method to predict the anatomical images of nasopharyngeal carcinoma patients during the treatment course, which could detect the anatomical variation for specific patients in advance.Methods:Imaging data including planning CT (pCT) and cone-beam CT (CBCT) for each fraction of 230 patients with T 3-T 4 staging nasopharyngeal carcinoma who treated in Cancer Hospital Chinese Academy of Medical Sciences from January 1, 2020 to December 31, 2022 were collected. The anatomical images of week k+1 were predicted using a 3D Unet model with inputs of pCT, CBCT on days 1-3, and CBCT of weeks 2- k. In this experiment, we trained four models to predict anatomical images of weeks 3-6, respectively. The nasopharynx gross tumor volume (GTV nx) and bilateral parotid glands were delineated on the predicted and real images (ground truth). The performance of models was evaluated by the consistence of the delineation between the predicted and ground truth images. Results:The proposed method could predict the anatomical images over the radiotherapy course. The contours of interest in the predicted image were consistent with those in the real image, with Dice similarity coefficient of 0.96, 0.90, 0.92, mean Hausdorff distance of 3.28, 4.18 and 3.86 mm, and mean distance to agreement of 0.37, 0.70, and 0.60 mm, for GTV nx, left parotid, and right parotid, respectively. Conclusion:This deep learning method is an accurate and feasible tool for predicting the patient's anatomical images, which contributes to predicting and preparing treatment strategy in advance and achieving individualized treatment.

Research progress of DNA methylation in the diagnosis and treatment of nasopharyngeal carcinoma / 中华检验医学杂志

Nasopharyngeal carcinoma is a common malignant tumor in southern China, and its occurrence and development mechanism are still not fully understood. However, a large number of studies have shown that DNA methylation has important clinical application value in the screening, diagnosis, treatment and prognosis evaluation of nasopharyngeal carcinoma. DNA methylation affects the division cycle, growth, invasion and migration of nasopharyngeal carcinoma cells by regulating the transcription and protein expression levels of genes associated with tumorigenesis and development. In addition, there are significant differences in DNA methylation expression levels in different stages of nasopharyngeal carcinoma, which provides theoretical guidance and clinical reference for the early diagnosis, timely treatment and response evaluation of nasopharyngeal carcinoma. Current studies have shown that DNA methylation detection may provide a simple and efficient early screening method for nasopharyngeal carcinoma, and can also explore new ideas for the development of non-invasive screening methods.

The value of IGFBP1 in the diagnosis and prognosis of nasopharyngeal carcinoma / 中国医师杂志

Objective:To explore the role of insulin-like growth factor binding protein 1 (IGFBP1) in the diagnosis and prognosis of nasopharyngeal carcinoma (NPC), and to search for molecular markers that can be used for the diagnosis of NPC.Methods:A retrospective analysis was conducted on 150 NPC patients (treated from April 2014 to May 2015) at the Cancer Hospital Affiliated to Shantou University Medical School, and clinical baseline data were collected from 143 healthy individuals (normal control group) during the same period. The serum IGFBP1 concentration was detected using enzyme-linked immunosorbent assay (ELISA) in 112 nasopharyngeal carcinoma patients and 109 normal controls in the training cohort, and was validated in the validation cohort (38 nasopharyngeal carcinoma patients and 34 normal controls). The diagnostic value of serum IGFBP1 in nasopharyngeal carcinoma was evaluated using the receiver operating characteristic curve (ROC).Results:Compared to the normal control group, the expression level of serum IGFBP1 in nasopharyngeal carcinoma patients was higher in the training and validation queues (all P<0.05). In the training queue, the area under the ROC curve was 0.768 (95% CI: 0.706-0.830), with diagnostic specificity and sensitivity of 90.83% and 48.21%, respectively. In the validation queue, the area under the ROC curve was 0.798 (95% CI: 0.697-0.899), with diagnostic specificity and sensitivity of 97.06% and 31.58%, respectively. The predictive values for positive cases in both cohorts were greater than 80%, while the predictive values for negative cases were greater than 50%. The diagnostic threshold for serum IGFBP1 in both cohorts was 1 077 ng/ml. Conclusions:IGFBP1 has practical value as a molecular marker for the diagnosis of nasopharyngeal carcinoma.

Correlation between the waiting time for radiotherapy and prognosis after induction chemotherapy for locally intermediate and advanced nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective:To investigate the correlation between the waiting time for radiotherapy after induction chemotherapy and the prognosis of locally intermediate and advanced nasopharyngeal carcinoma, as well as its optimal time.Methods:Retrospective analysis of 101 patients with locally intermediate and advanced nasopharyngeal carcinoma admitted to the Fifth Affiliated Hospital of Sun Yat-sen University from 2017 to 2020 was performed. All patients received at least 2 courses of induction chemotherapy followed by radical radiotherapy. The waiting time for radiotherapy was defined as the time from the end of induction chemotherapy to the start of the first radiotherapy. The relationship between waiting time for radiotherapy and other factors (age, gender and stage, etc.) with progression-free survival (PFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) was analyzed through Cox model. The median waiting time for radiotherapy with 3 weeks was used as the boundary, and all patients were divided into ≤3 weeks and>3 weeks groups. The PFS, LRFS and DMFS between two groups were compared using Kaplan-Meier survival analysis. P<0.05 was considered as statistical significance. Results:Cox-regression analysis showed that the waiting time was correlated with PFS, LRFS, and DMFS (all P<0.05). Kaplan-Meier survival analysis suggested that the PFS, LRFS and DMFS in the ≤3 weeks group were significantly better than those in the >3 weeks group (all P<0.05). Under the premises of the T 3 stage, N 2 stage and the increased EB virus DNA replication levels before treatment, the PFS, LRFS and DMFS in the ≤3 weeks group were significantly better than those in the >3 weeks group (all P<0.05). Conclusions:The waiting time for radiotherapy is one of the factors affecting clinical prognosis of locally intermediate and advanced nasopharyngeal carcinoma. The earlier the time, the better the prognosis. Radiotherapy should be delivered within 3 weeks.

Social alienation of survivors of nasopharyngeal cancer and its influencing factors / 中国实用护理杂志

Objective:To explore the status of social alienation among survivors of nasopharyngeal carcinoma and analyze its influencing factors.Methods:This study was a cross-sectional study. From October 2021 to January 2022, 200 survivors of nasopharyngeal carcinoma reviewed in the radiotherapy department of the First Affiliated Hospital of Guangxi Medical University were investigated by General Data Questionnaire, General Alienation Scale (GAS), Cancer Fatigue Scale (CFS) and Self-Perceived Burden Scale (SPBS).Results:The total score of GAS in survivors of nasopharyngeal carcinoma was (37.47 ± 2.88) points. The total scores of GAS were positively correlated with the total score and each dimension score of CFS and SPBS ( r values were 0.312-0.524, all P<0.01). Multivariable linear regression showed that the duration of diagnosis, whether or not having hearing loss, the number of symptoms, cancer fatigue and self-perceived burden were the main influencing factors of social alienation in survivors of nasopharyngeal carcinoma( t values were -3.99-4.86, all P<0.05), which could explain 49% of the total variation. Conclusions:Clinical medical staff should attach importance to social alienation of surviors of nasopharyngeal carcinoma. More attention should be paid to patients with less than one year of diagnosis, a large number of symptoms and hearing loss, and targeted intervention should be conducted to reduce the degree of social alienation of patients and promote their integration into society.

Establishing a model for predicting recurrence and metastasis in patients with advanced nasopharyngeal carcinoma / 中华检验医学杂志

Objective:To establish a risk assessment model for recurrence and metastasis in patients with advanced nasopharyngeal carcinoma.Methods:A survival follow-up study was conducted using a COX regression model to analyze 242 patients with advanced nasopharyngeal carcinoma who were treated for the first time in the Fudan University Shanghai Cancer Center from March 1, 2012 to August 31, 2020. The mean age was (48.33±11.13) years, with 178 males and 64 females. The mean survival was (3.39±1.42) years. According to the random number table method, the enrolled subjects were divided into two groups, including 192 cases in the modeling group and 50 cases in the validation group. Venous blood was collected from patients before treatment, after the first treatment and during the follow-up period after treatment. The blood cell classification and blood biochemical indicators were analyzed. T test and Chi-square test were used to analyze the difference in indicators in prognosis of patients with recurrence and metastasis as the outcome of the study. Multivariate COX regression analysis was used to screen out the independent prognostic factors affecting the recurrence and metastasis of nasopharyngeal carcinoma patients, and the Nomogram models of recurrence and metastasis risk of patients in 2 years, 4 years and 6 years were constructed. The model C-Index of the modeling group and the validation group were calculated to evaluate the performance of the predictive model.Results:White blood cells ( P=0.028), lymphocyte counts ( P<0.001), neutrophils ( P=0.001), platelets ( P=0.046), albumin ( P<0.001), neutrophil/lymphocyte ratio ( P<0.001), platelet/lymphocyte ratio ( P<0.001), lymphocyte/monocyte ratio ( P<0.001), systemic immune inflammatory response index ( P<0.001), systemic inflammatory response index ( P<0.001), and prognostic nutritional index ( P=0.004) had statistically significant differences in the efficacy monitoring of patients; through multivariate COX regression analysis, it was found that the platelet/lymphocyte ratio ( HR 2.537, 95% CI 1.439-4.473) and the prognostic nutritional index ( HR 0.462, 95% CI 0.236-0.903) are important factors to predict the risk of recurrence and metastasis of patients. Combining the above indicators, the Nomogram risk assessment model was established. The C index of the modeling group was 0.698, and the C index of the validation group was 0.739. The calibration curves of the two groups showed good consistency. Conclusion:The Nomogram evaluation model can accurately predict the risk of recurrence and metastasis in patients with nasopharyngeal carcinoma, and provide a theoretical basis for evaluating the prognosis of clinical treatment.

Application value of magnetic resonance imaging intravoxel incoherent motion diffusion-weighted imaging and texture analysis in differential diagnosis and staging of nasopharyngeal carcinoma / 肿瘤研究与临床

Objective:To investigate the application value of magnetic resonance imaging (MRI) intravoxel incoherent motion (IVIM)-diffusion-weighted imaging (DWI) metrics and texture analysis in the differential diagnosis and staging of nasopharyngeal carcinoma.Methods:The clinical data of 125 nasopharyngeal carcinoma patients (the research group) in Tangshan People's Hospital from October 2019 to October 2021 and 76 patients with nasopharyngeal hyperplasia during the same period (the control group) were retrospectively analyzed. All patients underwent MRI T2WI and IVIM-DWI sequence scanning, and then the plain T2WI images, DWI, and IVIM-DWI quantitative parameter pseudo-color maps including pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were obtained. The texture analysis metrics like apparent diffusion coefficient (ADC), D, D* and f were recorded. IVIM-DWI and texture analysis metrics were compared among patients in both groups and patients in different clinical stages; and the receiver operating characteristic (ROC) curve was plotted to evaluate the efficacy of IVIM sequence parameters and texture analysis metrics in the differential diagnosis and staging of nasopharyngeal carcinoma.Results:Compared with the control group, a marked reduction in D value [(0.80±0.13)×10 -3 mm 2/s vs. (1.19±0.27)×10 -3 mm 2/s], f value [(11.3±2.2)% vs. (15.6±3.3)%], mean ADC value [(0.92±0.17)×10 -3 mm 2/s vs. (1.16±0.19)×10 -3 mm 2/s] and variance (2 189±862 vs. 3 563±925) (all P < 0.05); a notable increase in skewness (0.50±0.17 vs. 0.31±0.12), kurtosis (0.56±0.13 vs. -0.21±0.06) and entropy (10.5±2.3 vs. 7.1±2.1) (all P < 0.05). The area under the curve (AUC) of IVIM sequence parameters and texture analysis metrics in the differential diagnosis of nasopharyngeal carcinoma was 0.763 and 0.803, respectively; the AUC, sensitivity and specificity of the combination of IVIM sequence parameters and texture analysis metrics for the differential diagnosis of nasopharyngeal carcinoma was 0.868, 89.6% and 86.8%, respectively. Compared with patients in stage Ⅰ-Ⅱ nasopharyngeal carcinoma, patients in stage Ⅲ-Ⅳ reported the lower D value [(0.75±0.13)×10 -3 mm 2/s vs. (0.89±0.16)×10 -3 mm 2/s], f value [(10.8±2.8)% vs. (12.1±3.0)%] (all P < 0.05), and the lower mean ADC value [(0.90±0.14)×10 -3 mm 2/s vs. (0.96±0.16)×10 -3 mm 2/s], and variance (2 063±831 vs. 2 431±846) (all P < 0.05), skewness (0.56±0.15 vs. 0.39±0.16), kurtosis (0.62±0.15 vs. 0.44±0.13) and entropy (11.0±2.1 vs. 9.1±2.4) (all P < 0.05). The AUC of IVIM sequence parameters and texture analysis metrics in differentiating nasopharyngeal carcinoma with different stages was 0.863 and 0.796, respectively; the AUC, sensitivity and specificity of the combination of IVIM sequence parameters and texture analysis metrics in differentiating nasopharyngeal carcinoma with different stages was 0.894, 85.4% and 90.7%, respectively. Conclusions:MRI texture analysis and IVIM quantitative analysis are of high value in the differential diagnosis and staging of nasopharyngeal carcinoma; and the texture analysis achieves higher sensitivity and specificity in the differential diagnosis and staging of nasopharyngeal carcinoma compared with IVIM quantitative analysis; the combined application of both has the highest overall efficacy.

Value of conventional MRI and high resolution diffusion weighted imaging in differentiation nasopharynx and skull base osteomyelitis from locoregionally advanced nasopharyngeal carcinoma / 中华放射学杂志

Objective:To investigate the value of conventional MRI and high resolution diffusion weighted imaging (DWI) for preoperative discrimination between nasopharyngeal-skull base osteomyelitis (NP-SBO) and locoregionally advanced nasopharyngeal carcinoma (LA-NPC).Methods:From January 2017 to October 2021, 27 patients of NP-SBO and 32 patients of LA-NPC were retrospectively analyzed at the Eye & ENT Hospital of Fudan University. The clinical characteristics and conventional MRI features were collected, and the apparent diffusion coefficient (ADC) values of polygonal (ADC polygonal) and small circle were measured from readout segmentation of long variable echo-trains (RESOLVE) DWI. MRI features included laterality, margin, signal intensity of T 1WI and T 2WI, enhancement degree, component, abscess, deep mucosal white line, bone invasion, lymph nodes involvement and other accompany symphtoms. The independent sample t test, χ 2 test or Fisher exact test were used to compare the features and ADC values of the NP-SBO and LA-NPC groups. The logistic regression was applied to select independent predictors in the distinguishing LA-NPC from NP-SBO. Then, the conventional MRI model, ADC model and conventional MRI in combination with ADC model were built. The area under the receiver operating characteristic curve (AUC) of models were compared using DeLong test. Results:The age, diabetic status, cranial nerve deficits, inner component, abscess, deep mucosal white line, lymph nodes involvement and ADC polygonal were significantly different between NP-SBO and LA-NPC groups ( P<0.05). The logistic regression analysis showed that ADC polygonal (OR=0.972, 95%CI 0.951-0.993, P=0.011) and abscess (OR=0.101, 95%CI 0.013-0.774, P=0.027) were the independent predictors in the discrimination of NP-SBO and LA-NPC. The AUC (95%CI) of conventional MRI model (abscess), ADC model (ADC polygonal) and combination model were 0.634 (0.499-0.756), 0.870 (0.757-0.943), and 0.925(0.829-0.979), respectively. The AUC of combination model was higher than that of conventional MRI model ( Z=4.77, P<0.001), while there was no difference between combination model and ADC model ( Z=1.87, P=0.062). The AUC of conventional MRI model was lower than that of ADC model ( Z=2.84, P=0.005). Conclusion:Conventional MRI in combination with RESOLVE DWI shows good performance in differentiating between NP-SBO and LA-NPC, especially for abscess in combination with ADC polygonal value.

MRI-based neck imaging reporting and data systems in diagnosis of extracavity local recurrent nasopharyngeal carcinoma and posttreatment changes / 中华放射学杂志

Objective:To evaluate the diagnostic value of neck imaging reporting and data systems (NI-RADS) based on MRI in extracavity local recurrent nasopharyngeal carcinoma (ELRNPC) and posttreatment changes (PTC).Methods:From April 2015 to September 2020, 33 cases of ELRNPC and 37 cases of PTC confirmed by pathology or follow-up were retrospectively enrolled at Zhongshan City People′s Hospital. Two radiologists independently evaluated the conventional MRI findings using NI-RADS criteria in the first step, then evaluated with conventional MRI and diffusion weighted imaging (DWI) sequences in the second step. All images were re-evaluated by one senior radiologist in the same steps after three months. Inter- and intra-reader agreements were assessed with Cohen′s Kappa test. Receiver operating characteristic curves were generated to assess the diagnostic values of NI-RADS categories between ELRNPC and PTC. The area under the curve (AUC) was compared by Delong test.Results:Inter- and intra-reader agreements of Kappa value were 0.742 and 0.909 for conventional MRI and 0.807 and 0.934 for conventional MRI with DWI. In the differential diagnosis of ELRNPC and PTC, the AUC, sensitivity, and specificity of NI-RADS categories based on conventional MRI were 0.932 (95%CI 0.846-0.978), 87.9% (95%CI 71.8%-96.6%), 94.6% (95%CI 81.8%-99.3%), and of NI-RADS based on conventional MRI with DWI were 0.991 (95%CI 0.933-1.000), 93.9% (95%CI 79.8%-99.3%), 97.3% (95%CI 85.8%-99.9%), respectively. There was a statistical difference between the AUCs of the two categories ( Z=2.20, P=0.028). Conclusions:For both the NI-RADS based on MRI with or without DWI, the differential diagnostic value of ELRNPC and PTC is excellent, while the consistency and diagnostic performance are more substantial when combined with DWI.

Prognostic value of 18F-FDG PET/CT metabolic parameters in locally recurrent nasopharyngeal carcinoma receiving chemoradiotherapy and their relationships with peripheral blood inflammation markers / 中华核医学与分子影像杂志

Objective:To investigate the prognostic value of 18F-FDG PET/CT in patients with locally recurrent nasopharyngeal carcinoma (NPC) receiving chemoradiotherapy, and relationships between different metabolic parameters and peripheral blood inflammation markers. Methods:From January 2013 to June 2016, the data of 56 patients (40 males, 16 females, age 27-81 years) with locally recurrent NPC receiving chemoradiotherapy in the First People′s Hospital of Foshan were retrospectively analyzed. The SUV max, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were determined by 18F-FDG PET/CT and peripheral blood inflammation markers within 1 week before treatment were measured. Spearman rank correlation analysis was used to estimate the correlations between metabolic parameters and inflammation markers. According to the ROC curve, the best cut-off values of the SUV max, MTV and TLG were obtained and used to group patients. The Kaplan-Meier method and Cox regression were used to conduct univariate analysis and multivariate analysis of 3-year locoregional failure-free survival (LRFFS) and 3-year overall survival (OS) in patients with locally recurrent NPC. The prognostic value of metabolic parameters in patients with early and advanced recurrent T(rT) stages were compared. Results:MTV was positively correlated with neutrophils, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and high-sensitivity C-reactive protein (hs-CRP) before treatment in patients with locally recurrent NPC ( rs values: 0.30, 0.30, 0.28, 0.27, all P<0.05); TLG was positively correlated with neutrophils, monocytes, NLR and PLR ( rs values: 0.30, 0.28, 0.32, 0.30, all P<0.05). But there were no correlations between SUV max and peripheral blood inflammation markers ( rs values: from -0.18 to 0.24, all P>0.05). SUV max was an factor affecting 3-year LRFFS of patients undergoing radiotherapy and chemotherapy (hazard ratio ( HR)=3.815(95% CI: 1.278-11.388), P=0.016), while rT stage and MTV were prognostic factors for 3-year OS ( HR values: 4.492(95% CI: 1.474-13.688), 7.238(95% CI: 1.653-31.688), P values: 0.008, 0.009). For patients with advanced rT (rT3-4), the 3-year OS of the MTV≥6.84 cm 3 group was significantly lower than that of MTV<6.84 cm 3 group ( χ2=6.99, P=0.008). Conclusions:SUV max of tumor and MTV before treatment have important prognostic values in patients with locally recurrent NPC receiving chemoradiotherapy, but their predictive effects on prognosis are not the same. The varying effects of local inflammation on metabolic parameters may be one of the important reasons lead to that difference.

Radiomics in nasopharyngeal carcinoma: current progress and challenges / 中华核医学与分子影像杂志

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck. In clinical practice, imaging examination plays an important role in the diagnosis, staging and risk assessment of NPC. However, it is difficult to distinguish the heterogeneity within the tumor, so the ability to classify and predict NPC is limited. Radiomics can extract a large amount of data from medical images for quantitative analysis, which further improves the ability of imaging features to diagnose and predict tumors. The purpose of this review is to introduce the application value of radiomics of different imaging modality such as CT, MRI and PET in differential diagnosis, predictions of treatment response, prognosis and radiotherapy complications of NPC.

Clinical research progress of immunotherapy for nasopharyngeal carcinoma / 国际肿瘤学杂志

Immunotherapy mainly uses the effector units of the body's immune system to overcome the immune escape or adaptive immune resistance of tumors, accurately identify and remove tumor cells, and normalize or enhance the function of the immune system, which mainly includes cytokine therapy, immune checkpoint inhibition therapy, adoptive cell immunotherapy, tumor vaccine and antibody targeted therapy. The immune characteristics of nasopharyngeal carcinoma make the patients potentially suitable for immunotherapy or combined therapy with radiotherapy and chemotherapy. In recent years, PD-1 inhibitors alone and in combination with chemotherapy have shown good anti-tumor activity and safety in the treatment of recurrent/metastatic nasopharyngeal carcinoma. The incorporation of immune checkpoint inhibitors into the treatment paradigms of nasopharyngeal carcinoma has become a clinical research hot spot.

Effects of miR-363-5p on proliferation and apoptosis of nasopharyngeal carcinoma cells and the possible mechanism / 中国基层医药

Objective:To investigate the effects of miR-363-5p on the proliferation and apoptosis of nasopharyngeal carcinoma cells and the possible mechanism.Methods:miR-363-5p expression in human normal nasopharyngeal epithelial cells NP-69 and nasopharyngeal carcinoma cells 5-8F was detected using quantitative real-time polymerase chain reaction. Proliferation and apoptosis of 5-8F cells overexpresing miR-365-5p were determined. At the same time, Caspase3 and BRD4 protein expression in 5-8F cells were also detected.Results:miR-365-5p expression in 5-8F cells (0.71 ± 0.45) was significantly lower than that in NP-69 cells ( t = 2.68, P < 0.05). After overexpressing miR-363-5p, the proliferation of 5-8F cells was significantly decreased ( F = 22.68, P < 0.05). The apoptotic rate in the 5-8F cells was significantly higher than that in the control group [(24.45 ± 5.38)% vs. (18.23 ± 2.41)%, t = 4.13, P < 0.05]. Bax and Caspase3 protein levels in the 5-8F cells were (1.35 ± 0.24) and (1.44 ± 0.34) respectively, which were significantly higher than those in the NP-69 cells [(1.00 ± 0.08), (1.00 ± 0.23), t = 3.12, 5.12, P < 0.05]. BRD4 protein level in the 5-8F cells was significantly lower than that in the control group [(0.42 ± 0.24) vs. (1.00 ± 0.37), t = 2.98, P <0.05]. Conclusion:miR-365-5p can inhibit proliferation of nasopharyngeal carcinoma cells and promote their apoptosis. The negative regulatory effects of miR-363-5p on tumor cells are achieved possibly through inhibiting BRD4 protein expression.

Clinical significance and expression of inhibin βB in nasopharyngeal carcinoma and lung adenocarcinoma / 中国医师杂志

Objective:To investigate the expression of inhibin β B (INHBB) in nasopharyngeal carcinoma (NPC) and lung adenocarcinoma (LUAD) and its relationship with clinicopathological features.Methods:Paraffin-embedded tissue specimens of 39 patients with NPC and 16 patients with chronic nasopharyngitis diagnosed by biopsy, and 30 patients with LUAD after surgical resection collected in Brain Hospital of Hunan Province (the Second People′s Hospital of Hunan Province) were analyzed retrospectively. The expression of INHBB in NPC and LUAD was detected by immunohistochemical streptavidin-perosidase (SP) method and the relationship of INHBB expression level with clinicopathological indicators was analyzed.Results:The expression of INHBB in NPC was lower than that in chronic nasopharyngitis (51.28% vs 81.25%, P=0.039), and the expression of INHBB was related to lymph node metastasis ( P=0.026) and clinical stage ( P=0.039); On the contrary, the expression level of INHBB in LUAD was significantly higher than that in adjacent tissues (86.67% vs 23.33%, P<0.001). The expression level of INHBB in patients with LUAD was only related to clinical stage ( P=0.048). Conclusions:The expression of INHBB might play an important role in the development and progression of NPC and LUAD, and it was expected to be a novel diagnostic biomarker.

Nomogram for predicting the response to chemoradiotherapy in advanced nasopharyngeal carcinoma based on arterial spin-labeled perfusion parameters and clinicopathological features / 中华放射学杂志

Objective:To explore the value of nomogram based on arterial spin labeling (ASL) MRI perfusion parameters and clinicopathological features in predicting the response to chemoradiotherapy (CRT) in advanced nasopharyngeal carcinoma (ANPC, stage Ⅲ and Ⅳ).Methods:From June 2018 to January 2021, 70 patients with ANPC confirmed by pathology were prospectively enrolled in Affiliated Hospital of Jiangnan University. Nasopharyngeal MRI plain scan, ASL and contrast-enhanced scan were performed before CRT, and routine MRI re-examination was performed within 1 week after the end of CRT. The pre-CRT perfusion parameter tumor blood flow (TBF) from ASL and clinicopathological features were recorded, and the maximum diameter (MD) of the tumor on T 1WI images was measured. The patients were divided into CRT effective group (48 cases) and ineffective group (22 cases) according to the response evaluation criteria in solid tumors. The independent sample t test was used to compare the differences of TBF, age and MD between effective group and ineffective group. The χ 2 test was used to compare the differences of gender, clinical stage and pathological type between the 2 groups. Using binary logistic regression analysis, clinicopathological model and TBF combined clinicopathological model were constructed, and the nomogram of combined model was constructed. The diagnostic efficacy of the models was obtained by receiver operating characteristic (ROC) curve analysis, and the area under the ROC curves (AUC) of the 3 models were compared by DeLong method. The calibration curve for the nomogram was generated, and the concordance index (C index) was acquired. Results:The TBF of the effective group and the ineffective group were (113±9) and (97±14) ml·100 g -1·min -1, with a statistical difference ( t=5.17, P<0.001). The MD value of the effective group was smaller than that of the ineffective group, with a statistical difference ( t=-2.24, P=0.028). There were statistical differences in clinical stage and pathological type between the 2 groups (χ 2 values were 12.21 and 12.95, respectively, both P<0.001). Three independent predictors, including TBF (OR=7.749), clinical stage (OR=0.129) and pathological type (OR=5.228), were included in logistic regression analysis. The AUC, sensitivity and specificity of TBF model in predicting the response to CRT were 0.843, 87.5% and 72.7%, of clinicopathological model were 0.822, 80.2% and 59.1%, of the nomogram model were 0.893, 81.2% and 90.9%. There was no statistical difference of AUC between the nomogram model and TBF model ( Z=1.23, P=0.215). However, the AUC of the nomogram model was greater than that of the clinicopathological model ( Z=2.47, P=0.031). The calibration curve showed that there was a good concordance index (C index=0.892) between the predicted value of nomogram and the actual clinical observation value. Conclusion:TBF, clinical stage and pathological type are independent predictors of the response to CRT in ANPC patients, and the nomogram based on these three factors has a good ability in predicting the response to CRT.

Quantitative evaluation of sternocleidomastoid muscle fibrosis after radiotherapy for nasopharyngeal carcinoma based on mapping technique of MRI / 中华放射学杂志

Objective:To investigate the feasibility and clinical value of MRI quantitative evaluation technique in detecting sternocleidomastoid muscle fibrosis in patients with nasopharyngeal carcinoma (NPC) after radiotherapy.Methods:From August 2019 to March 2021, 45 patients with clinically confirmed NPC after radiotherapy and 30 healthy controls who underwent physical examination in Lishui Hospital of Zhejiang University were enrolled in our study. According to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) classification criteria of late radiation reactions respectively, the sternocleidomastoid muscle injury in the NPC group was divided into grade Ⅰ, Ⅱ and Ⅲ, which included 8, 32 and 5 patients respectively. All patients underwent T 1 mapping and T 2 mapping imaging of the neck. Firstly, the mapping images of sternocleidomastoid muscle between the two groups were analyzed and compared. Using NUMARIS/4 software of Siemens image post-processing workstation, the region of interest was manually drawn along the edge of sternocleidomastoid muscle at the level of laryngeal chamber in axial mapping diagram. Then, T 1 and T 2 values and the long and short diameters of sternocleidomastoid muscle were measured respectively. Finally, the differences of the parameters between the two groups were compared by independent sample t-test, Spearman rank correlation was used to analyze the relationship between the average T 1 and T 2 values of bilateral sternocleidomastoid muscles and the grade of late radiation injury. Results:Compared with the control group, the shape of sternocleidomastoid muscle in the NPC group was smaller in shape, with irregular edge and uneven increase of T 1 mapping color scale. There was no significant difference in muscle signal in T 2 mapping. The T 1 values of left and right sternocleidomastoid muscles in the NPC group were (1 524.7±97.6) and (1 496.5±93.2) ms respectively, which were significantly higher than those in the normal control group [(1 231.5±85.3) and (1 275.9±90.9) ms] ( P<0.05), and the T 2 values of left and right sternocleidomastoid muscles in the NPC group were (28.4±4.8) and (28.4±3.6) ms respectively, which were lower than those in the normal control group [(30.4±3.5) and (30.4±3.5) ms] ( P<0.05). The long and short diameters of bilateral sternocleidomastoid muscles in the NPC group were shorter than those in the control group ( P<0.05). The average T 1 and T 2 values of bilateral sternocleidomastoid muscles in NPC patients after radiotherapy were (1 510.6±95.4) and (28.4±4.2) ms respectively, The T 1 value was positively correlated with the classification of advanced radiation injury ( r=0.78, P<0.001), and T 2 value was negatively correlated with the level of advanced radiation injury ( r=-0.87, P<0.001). Conclusion:Mapping quantitative evaluation technique can noninvasively and objectively detect and evaluate sternocleidomastoid muscle fibrosis after NPC radiotherapy, which has potential clinical application value.

Value of plasma Epstein-Barr virus DNA detection in the screening of nasopharyngeal carcinoma and its clinical application in non-high-risk areas / 中华检验医学杂志

Objective:To investigate the value of plasma Epstein-Barr virus (EBV) DNA detection in the screening of nasopharyngeal carcinoma (NPC) and its clinical application in non-high-risk areas.Methods:Plasma EBV DNA results in 1 153 newly diagnosed nasopharyngeal carcinoma patients who were treated in Sichuan Cancer Hospital from 2015 to 2020 and 244 healthy control cases with matched sex and age were retrospectively analyzed. EBV DNA were detected by quantitative real-time PCR. Positive rate of EBV DNA was determined by the cutoff value of 400 (≥400 copies/ml as positive) and optimization threshold method (presence of S amplification curve as positive). Further analyses were conducted to compare EBV DNA load in different clinical stage, TNM stage and regions distribution characteristics. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of the cutoff value of 400 and optimization threshold method for NPC.Results:Compared with healthy controls, EBV DNA increased significantly in newly diagnosed NPC patients ( P<0.001). Both evaluation methods revealed that the EBV DNA positive percentage increased with TNM and clinical stage ( P<0.001). With 400 copies/ml as cutoff value, the diagnostic sensitivity and specificity were 40.85% and 100%, respectively. The area under the curve was 0.704 (95% CI 0.676-0.733, P<0.001). Evaluated by the optimization threshold method, the sensitivity and specificity could improve to 82.0% and 99.2%, respectively, and the area under the curve reached 0.910 (95% CI 0.894-0.924, P<0.001). Conclusions:In the low prevalence area of nasopharyngeal carcinoma, the sensitivity for diagnosis of nasopharyngeal carcinoma is only 40.9% by the 400 copies/ml cutoff value method. The optimization threshold method is a better choice to improve the diagnostic sensitivity without lowering the diagnostic specificity.

Prognostic differences of nasopharyngeal carcinoma patients treated with intensity-modulated radiothe-rapy with different T staging of the seventh and eighth edition of the UICC staging system / 国际肿瘤学杂志

Objective:To compare the differences in population distribution and prognosis of patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) in T staging of the Union for International Cancer Control (UICC) 7th edition and UICC 8th edition, and to analyze the prognostic factors in patients with NPC.Methods:The clinicopathologic date of 184 patients with newly diagnosed NPC treated with IMRT at the Department of Radiation Oncology of Weifang People′s Hospital of Shandong Province from June 1, 2005 to December 31, 2017 were retrospectively analyzed. All patients were restaged according to the 7th and 8th edition of the UICC staging system. The distribution of T staging of patients in the two staging systems was analyzed, and the consistency of the two staging systems was compared using the Kappa consistency test. Kaplan-Meier method was used for survival analysis, and log-rank test was used to compare the prognostic differences among T stages. Cox regression model was used to analyze the prognostic factors of patients with NPC.Results:Of all 184 patients with NPC, stage T 1, T 2, T 3 and T 4 respectively accounted for 18.5% (34/184), 16.8% (31/184), 15.2% (28/184) and 49.5% (91/184) according to the 7th edition UICC staging system. However, stage T 1, T 2, T 3 and T 4 respectively accounted for 18.5% (34/184), 34.2% (63/184), 30.4% (56/184) and 16.8% (31/184) according to the 8th edition UICC staging system. The T staging population distribution of the two staging systems showed moderate consistency (Kappa=0.58). There was a statistically significant difference in overall survival (OS) among patients with stage T 1, T 2, T 3, T 4 according to the 7th edition UICC staging system ( χ2=10.606, P=0.014). There were statistically significant differences in OS between stage T 1 and stage T 2, T 3, T 4 ( χ2=4.866, P=0.027; χ2=11.965, P=0.001; χ2=4.351, P=0.037). The OS curves of stage T 2 and T 4 could not be separated. Moreover, the OS curves of stage T 3 and T 4 were distributed in reverse order. There was a statistically significant difference in OS among patients with stage T 1, T 2, T 3, T 4 according to the 8th edition staging system ( χ2=8.663, P=0.034). There were statistically significant differences in OS between stage T 1 and stage T 3, T 4( χ2=8.746, P=0.003; χ2=7.580, P=0.006). The OS curves of stage T 1 to T 4 were distributed in order, but the curves of stage T 3 and T 4 could not be separated. There was a statistically significant difference in progression-free survival (PFS) among patients with stage T 1, T 2, T 3, T 4 according to the 7th edition UICC staging system ( χ2=11.289, P=0.010). There were statistically significant differences in PFS between stage T 1 and stage T 2, T 3, T 4 ( χ2=8.209, P=0.004; χ2=13.302, P<0.001; χ2=6.550, P=0.010). The PFS curves of stage T 2 and T 4 could not be separated. Moreover, the PFS curves of stage T 3 and T 4 were distributed in reverse order. There was a statistically significant difference in PFS among patients with stage T 1, T 2, T 3, T 4 according to the 8th edition staging system ( χ2=12.074, P=0.007). There were statistically significant differences in PFS between stage T 1 and stage T 2, T 3, T 4( χ2=5.182, P=0.023; χ2=11.217, P=0.001; χ2=10.174, P=0.001). The PFS curves of stage T 1 to T 4 were distributed in order, but the curves of stage T 3 and T 4 could not be separated. The results of Cox multivariate analysis showed that T staging of both staging systems were the independent prognostic factors of the OS ( P=0.013; P=0.026) and PFS ( P=0.031; P=0.012). However, T staging of the two editions were not the independent prognostic factors of the local recurrence-free survival (LRFS) ( P=0.351; P=0.167) and distant metastasis-free survival (DMFS) ( P=0.059; P=0.052). The age was the independent prognostic factor of the OS ( HR=2.70, 95% CI: 1.53-4.76, P=0.001; HR=2.74, 95% CI: 1.55-4.84, P=0.001), PFS ( HR=2.72, 95% CI: 1.46-5.08, P=0.002; HR=2.94, 95% CI: 1.57-5.52, P=0.001), LRFS ( HR=5.87, 95% CI: 1.62-21.27, P=0.007; HR=6.02, 95% CI: 1.61-22.49, P=0.008) and DMFS ( HR=2.40, 95% CI: 1.22-4.72, P=0.011; HR=2.63, 95% CI: 1.34-5.18, P=0.005). N staging was the independent prognostic factor of the OS ( P=0.031; P=0.028). Conclusion:The T staging population distribution of the 7th and 8th edition UICC staging system had moderate consistency, and the T staging of the 8th edition is more advantageous in predicting the prognosis of OS and PFS. In both editions, T staging is an independent prognostic factor for OS and PFS.

Study of plasma matrix metalloproteinase-2 and matrix metalloproteinase-9 level during concurrent chemoradiotherapy and clinicopathologic significance in patients with nasopharyngeal carcinoma / 中国医师杂志

Objective:To investigate the changes of the plasma matrix metalloproteinase (MMP)-2 and MMP-9 levels and their clinical significances during the course of concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients.Methods:From January 2018 to June 2019, 46 patients with nasopharyngeal carcinoma were treated in the department of oncology, Changsha Central Hospital Affiliated to Nanhua University. All patients were confirmed by pathology. They were divided into early NPC group ( n=32) and invasive NPC group ( n=16) according to the degree of invasion. The early NPC group was treated with concurrent chemoradiotherapy alone, and the invasive NPC group was treated with neoadjuvant chemotherapy combined with concurrent chemoradiotherapy. Blood samples were collected at four stages of the treatment, and the concentrations of MMP-2 and MMP-9 were detected by enzyme linked immunosorbent assay (ELISA). Results:The longer the treatment time, the lower the concentration of MMP-9 ( P=0.007) in early NPC group; There was no significant difference in MMP-9 level before treatment, after neoadjuvant chemotherapy, after concurrent chemoradiotherapy, at the end of treatment and the first follow-up ( P>0.05) in invasive NPC group. There was no significant difference in the content of MMP-2 between the two groups before and after treatment ( P>0.05). There was no correlation between serum MMP-2 and MMP-9 levels and tumor stage, lymph node metastasis, tumor invasion and response rate ( P>0.05) in invasive NPC patients, while the level of MMP-9 was positively correlated with white blood count (WBC) and neutrophil count ( r=0.85, P=0.004, r=0.82, P=0.003); The ratio of MMP-9/MMP-2 was positively correlated with WBC and neutrophil count ( r=0.86, P=0.003, r=0.83, P=0.001). Conclusions:Synchronous radiotherapy and chemotherapy can reduce the serum MMP-9 level in early stage NPC patients, but it has no effect on the serum MMP-9 level in patients with invasive NPC, which suggests that synchronous radiotherapy and chemotherapy can not prevent the proliferation and distant metastasis of cancer cells in patients with invasive NPC.

A comparative study on the delineation of gross tumor volume and lymph nodes of nasopharyngeal carcinoma patients using CT/MRI/and PET-CT / 中华放射医学与防护杂志

Objective:To compare the differences in the delineation of the gross tumor volume (GTV) and lymph nodes of nasopharyngeal carcinoma (NPC) patients using computerized tomography (CT), magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT), and to investigate the optimal standard uptake value (SUV; relative to the MRI-based delineation) for the automatic delineation of GTV using PET. Methods:A total of 53 NPC patients proposing to receive radiotherapy were selected for this study. The CT, MRI, and PET images of each patient were obtained before radiotherapy. Then GTV and positive lymph nodes were delineated on these three types of images. They were individually named GTV MRI, GTV CT, GTV PET2.5 (SUV=2.5), Lymph MRI, Lymph CT, and Lymph PET2.5 and compared. The GTV ∩2.5 (overlapped GTV) was obtained through the alignment of MRI and PET/CT images. Meanwhile, GTV was delineated on PET images using thresholds of SUV=4.0, 4.5, 5.0, and 5.6, obtaining GTV PET4.0, GTV PET4.5, GTV PET5.0, and GTV PET5.6. Then their volume and Dice similarity coefficients (DSCs) were compared. Results:Compared to GTV MRI, GTV CT decreased by 1.73% ( P>0.05) and GTV PET2.5 increased by 21.34% ( t=-3.52, P < 0.05) in the three types of images. The volume of Lymph PET2.5 was 1.61 and 1.87 times the volume of Lymph MRI and Lymph CT, respectively ( t=-4.12, -5.18; P< 0.05). The volume of high-SUV lymph nodes was 4.07 times the volume of lymph nodes with low SUVs or SUV=0 ( t=5.50, P< 0.05) on PET images. The DSC between GTV PET4.0and GTV MRI was 0.78 ± 0.27, which was lower than that between GTV PET2.5 and GTV MRI (0.84 ± 0.18). However, GTV PET4.0 approximated to GTV ∩2.5 ( P>0.05). Conclusions:Compared to CT and 18F-FDG PET/CT, MRI shows more accurate boundaries of GTV and lymph nodes. When 18F-FDG PET/CT was adopted to automatically delineate GTV, the GTV delineated using SUV=4.0 was closer to GTV MRI.