Chinese Journal of Radiation Oncology

中华放射肿瘤学杂志

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Chinese Journal of Radiation Oncology

	2021 Vol.30 Issue.5 Published 2021-05-15

	Head and Neck Tumors Abdominal Tumors Thoracic Tumors Review Articles Investigation Research Physics·Technique·Biology

Investigation Research

	429	Enlightenment and reference of training and certification mode of radiation therapist in the United States
		Liu Jiping, Xu Junliang, Zhang Yin, Zhong Renming, Shan Guoping, Chen Wei
		The training program of radiation therapists in the United States has been established early, and the mode of training, qualification and continuing education are relatively complete. Literature review was conducted at home and abroad and United States Department of Labor, American Registry of Radiologic Technologists, American Society of Radiologic Technologists as well as Joint Review Committee on Education in Radiologic Technology websites were reviewed. The training mode, qualification, work content, continuing education and employment situation of American radiotherapists were analyzed, aiming to provide some reference and enlightenment for the establishment of a new model for the training of professional radiologists suitable for the national conditions of China Mainland.
		2021 Vol. 30 (5): 429-433 [Abstract] ( 256 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Head and Neck Tumors

	434	Effect of different induction chemotherapy on clinical prognosis of patients with non-endemic locally-advanced nasopharyngeal carcinoma after concurrent chemotherapy with IMRT
		Sun Xueming, Lu Xiaoxu, Huang Rong, Wu Hui
		Objective To evaluate effect of different induction chemotherapy on the clinical efficacy of concurrent intensity-modulated radiotherapy (IMRT) and chemotherapy and identify the prognostic factors in non-endemic locally-advanced nasopharyngeal carcinoma patients. Methods Clinical data of 210 patients with stage Ⅲ-ⅣB(excluding stage T3-4N0M0) nasopharyngeal carcinoma treated in our hospital from 2012 to 2017 were retrospectively analyzed. According to the efficacy of different induction chemotherapy, all patients were divided into the effective group (14 cases of complete remission and 165 cases of partial remission) and ineffective group (31 cases of stability and 0 case of progression). Survival analysis was performed by Kaplan-Meier method. Multivariate analysis was conducted by using Cox′s regression model. Results Compared with the ineffective group, the 3-year overall survival (OS)(89.2% vs. 74.2%, P=0.005), recurrence-free survival (RFS)(93.0% vs. 81.9%, P=0.010) and progression-free survival (PFS)(80.2% vs. 58.1%, P=0.005) were significantly higher in the effective group, whereas the distant metastasis-free survival did not significantly differ between two groups (84.1% vs.69.7%, P=0.070). Multivariate analysis showed that the tumor response to induction chemotherapy was an independent prognostic factor for OS, RFS and PFS. Conclusions Tumor response to induction chemotherapy might be a prognostic factor for non-endemic locally-advanced nasopharyngeal carcinoma patients. Clinical prognosis of patients with poor response to induction chemotherapy is even worse. More intensive treatment and closer follow-up may be needed for these patients.
		2021 Vol. 30 (5): 434-439 [Abstract] ( 249 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	440	Effect of CTV dose optimization in upper and middle neck on protecting the main midline structures in intensity-modulated radiotherapy for nasopharyngeal carcinoma
		Xu Wenjing, Chen Zhenzhang, Wang Lijun, Wen Jing, Liu Degan, Yu Jianhe, Huang Shengfu, He Xia
		Objective To explore the significance of the clinical target volume (CTV) dose optimization in the upper and middle neck in protecting the laryngopharynx, anterior and posterior rings during intensity-modulated radiotherapy (IMRT) and multimodal imaging system for nasopharyngeal carcinoma. Methods Clinical data of 298 nasopharyngeal carcinoma patients admitted to Jiangsu Cancer Hospital from 2016 to 2018 were retrospectively analyzed. According to the following five strategies of CTV dose optimization in the upper and middle neck:group A, complete optimization of bilateral cervical lymph nodes (CLNs), that is, the CTV doses of bilateral CLNs were 50.4Gy;group B, complete optimization of unilateral CLNs, that is, the CTV dose of unilateral CLNs was 50.4Gy and the contralateral CLNs was 60Gy;group C, incomplete optimization of bilateral CLNs, that is, the CTV doses of bilateral CLNs were 50.4Gy, while the suspicious positive CLNs were selectively boosted to 60Gy;group D, incomplete optimization of unilateral CLNs, that is, the CTV dose of unilateral CLNs was 50.4Gy and the suspicious positive CLNs were selectively boosted to 60Gy, and the CTV dose of contralateral side was 60Gy;group E:no optimization, that is, the CTV doses of bilateral CLNs were 60Gy. Results Among 298 patients, 215 patients received dose optimization and 83 cases did not receive dose optimization. In the dose optimization schemes, 114 cases were assigned in group A, 36 cases in group B, 60 cases in group C and 5 cases in group D. The median (range) follow-up time was 28.5(6.0-46.3) months. The overall survival rate was 95.6%, the progression-free survival rate was 84.2% and the locoregional control rate of CLNs was 98.0%. Local relapse of CLNs occurred in six patients, including 1 case of retropharyngeal lymph node, 4 cases of Ⅱ area and 1 case of Ⅳ area. The P values of average dose of laryngopharynx in group A, group B, group C and group D compared with that in group E were<0.001, 0.016, 0.001 and 0.572, respectively. The P values of the average dose of the anterior ring in group A, group B, group C and group D compared with that in group E were<0.001, 0.011,<0.001 and 0.805, respectively. The P values of the average dose of the posterior ring in group A, group B, group C and group D compared with that in group E were<0.001, 0.004,<0.001 and 0.252, respectively. Conclusions Combined with the metastatic rules of CLNs and multimodal imaging system, it is safe to optimize the CTV dose of the upper and middle neck during IMRT in nasopharyngeal carcinoma patients, which can significantly reduce the doses of laryngopharynx, anterior and posterior rings, thereby providing evidence for reducing the CTV dose in the upper and middle neck.
		2021 Vol. 30 (5): 440-445 [Abstract] ( 255 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	446	Effect of MGMT gene methylation status on chemoradiotherapy and prognosis in elderly patients with glioblastoma
		Sun Yafang, Wang Zheng, Shi Xiangyu, Du Fangfang, Jiang Wei
		Objective To investigate the effect of O-6-methylguananine-DNA methyltransferase (MGMT) gene promoter methylation status on the treatment and prognosis of elderly patients newly-diagnosed with glioblastoma (GBM). Methods Clinical data of 65 newly-diagnosed GBM patients admitted to Tianjin Huanhu Hospital from January 2012 to December 2018 were retrospectively analyzed. All patients received intensity-modulated radiotherapy after surgery and 49 patients received temozolomide (TMZ) monotherapy. All patients were divided into the MGMT(+) group and MGMT(-) group according to the methylation status of MGMT promoter. Kaplan-Meier method and log-rank test were used for univariate survival analysis, and Cox regression model was used for multivariate prognostic analysis. Results The median overall survival (OS) for all patients was 18.0 months. The median OS was 27.0 months and 15.3 months in the MGMT(+) group and MGMT(-) group, respectively. Univariate analysis revealed that tumor number, MGMT promoter methylation, postoperative concurrent chemoradiotherapy were significantly related to clinical prognosis (P=0.029, P=0.001 and P<0.001). In multivariate analysis, tumor number and postoperative concurrent chemoradiotherapy were identified as significant prognostic factors for OS (P=0.037,P=0.004). In the MGMT(+) group, the median OS was 27.0 months for patients receiving concurrent chemoradiotherapy and 12.0 months for radiotherapy alone (P=0.040). In the MGMT(-) group, the median OS was 17.0 months for concurrent chemoradiotherapy patients and 10.0 months for radiotherapy alone (P=0.122). Conclusions MGMT promoter methylation status is significantly associated with longer OS in elderly GBM patients. Conventional fractional radiotherapy combined with concurrent and sequential TMZ chemotherapy probably yields better survival benefits.
		2021 Vol. 30 (5): 446-450 [Abstract] ( 262 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Thoracic Tumors

	451	Efficacy of postoperative radiotherapy and prognosis in patients with completely resected stage Ⅲ(pN2) lung adenocarcinoma with EGFR wild-type receiving adjuvant chemotherapy
		He Chunyu, Ma Cong, Chen Huijing, Nie Xin, Li Peng, Wu Xiaoyuan, Zhang Chengjuan, Wang Zongfei, Liu Baoxing, Liu Ru, Ge Hong
		Objective To evaluate the value and identify the prognosic factors of postoperative radiotherapy (PORT) in completely resected stage Ⅲ(pN2) lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) wild-type who received adjuvant chemotherapy. Methods Clinical data of 172 patients with stage Ⅲ(pN2) EGFR wild-type lung adenocarcinoma who underwent radical resection and adjuvant chemotherapy from 2009 to 2016 were retrospectively analyzed. All patients received platinum-based adjuvant chemotherapy combining two drugs for>4 cycles, and divided into the PORT group and the non-PORT group. The survival rate was calculated by Kaplan-Meier method and log-rank test, and multivariate prognostic analysis was performed by Cox’s regression model. Results Among 172 patients, the median overall survival (OS), 3-year and 5-year OS rates were 40 months, 55.9% and 28.3%, respectively. The median disease-free survival (DFS), 3-year and 5-year DFS rates were 17 months, 24.5% and 13.0%, respectively. DFS was significantly improved in the PORT group (29 months vs. 13 months, P=0.001), whereas OS did not significantly differ between two groups (51 months vs. 38 months,P=0.151). In subgroup analysis,DFS of patients with multistation N2 or the number of N2 metastases of≥3 or skip N2 in the PORT group was significantly longer (P<0.05), whereas PORT exerted no significant effect on OS (P>0.05). Conclusions For patients with completely resected stage Ⅲ(N2) EGFR wild-type lung adenocarcinoma receiving adjuvant chemotherapy, PORT might increase DFS and have a trend toward longer OS. However, these findings remain to be validated by large sample size investigations.
		2021 Vol. 30 (5): 451-456 [Abstract] ( 186 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Abdominal Tumors

	457	Changes of multimodality therapeutic patterns of care study for resectable gastric cancer
		Xing Pengfei, Zhou Ning, Yang Yongqiang, Zhang liyuan, Tian Ye
		Objective To investigate and analyze the current status of multimodality therapy for resectable gastric cancer, aiming to provide reference for optimizing the multimodality treatment strategy for gastric cancer. Methods Clinical data of patients diagnosed with gastric adenocarcinoma undergoing radical gastrectomy in the Second Affiliated Hospital of Soochow University were retrospectively analyzed. Clinical characteristics, preoperative medical comorbidities,pathological features, surgical and perioperative status and clinical efficacy were recorded. The gap between the diagnosis and treatment procedures and the standard guidelines was analyzed. The changes in the multimodality treatment patterns for gastric cancer were understood. Results A total of 265 patients were included in this study. All patients were divided into two cohorts:early[2008] and late[2013] cohorts. In the early cohort, 127 patients were assigned, and 138 cases in the late cohort. In the early cohort, 67 patients (52.8%) underwent D2 lymph node dissection, significantly less than 83 patients (60.1%) in the late cohort (P<0.01). In the early and late cohorts, the proportion of patients with the number of lymph node dissection of ≥15 was 5.5% and 52.8%(P<0.01). The median number of lymph node dissection was increased from 6 to 16. The proportion of patients receiving neoadjuvant chemotherapy in the early and late cohorts was 2.4% and 3.6%(P=0.55). In the early cohort,the proportion of patients treated with postoperative chemotherapy and postoperative adjuvant chemoradiotherapy was 62.6% and 2.4%, significantly higher compared with 58.0% and 8.0% in the late cohort (P=0.04). In addition, the proportion of patients receiving postoperative chemotherapy in the early cohort was 62.2%(n=79) and 58.0%(n=80) in the late cohort (P=0.48). Conclusions Although the level of radical gastrectomy has been continuously improved and standardized in China, which still lags behind the standard D2 radical gastrectomy in Japan and South Korea. Adjuvant therapies including postoperative adjuvant radiotherapy can bring clinical benefits. However, the proportion of patients receiving adjuvant therapy is still low, and the multimodality therapy of gastric cancer should be widely applied.
		2021 Vol. 30 (5): 457-461 [Abstract] ( 161 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	462	Comparison of different local treatment patterns in breast cancer with ipsilateral supraclavicular lymph node metastasis
		Liu Zhikun, Li Xiaohong, Zhu Longyu, Han Huina, Zhang Andu, Duan Xuejuan, Shang Yuguang, Shen Dongxing, Pei Ling, Jia Sicong, Zhu Li, Zhang Jun
		Objective To explore the optimal local treatment pattern of supraclavicular lymph node in breast cancer patients with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM). Methods Clinical data of 128 breast cancer patients with sISLM admitted to the Fourth Hospital of Hebei Medical University from 2010 to 2015 were retrospectively analyzed. Among them, 68 cases were treated with supraclavicular lymph node dissection combined with radiotherapy, and 60 cases received radiotherapy alone. The locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were statistically compared between two groups. Results Univariate analysis demonstrated that the 5-year LRFS,DMFS,PFS and OS did not significantly differ between two groups (all P>0.05). Multivariate analysis revealed that the local treatment pattern of supraclavicular lymph node was an independent prognostic factor for the 5-year DMFS, PFS and OS (all P<0.05). Subgroup analysis showed that when radiotherapy alone was performed, the 5-year OS of patients in the supraclavicular region radiation doseof>50Gy group were significantly better than that in the 50Gy group (P=0.047). When supraclavicular lymph node dissection combined with radiotherapy was delivered, if the number of dissection was less than 10, the 5-year LRFS, DMFS, PFS, OS of patients in the>50Gy group were all better than those in the 50Gy group numerically without statistical significance (all P>0.05). If the number of dissection was ≥10, the 5-year LRFS, DMFS, PFS, OS in the 50Gy group were better than those in the>50Gy group numerically, whereas significant difference was only found in the 5-year DMFS (P=0.028). Conclusions Supraclavicular lymph node dissection combined with radiotherapy may be the optimal local treatment pattern for supraclavicular lymph node. When radiotherapy alone is performed, a radiation boost to the supraclavicular region may improve OS. When supraclavicular lymph node dissection combined with radiotherapy is performed, if the degree of dissection is low, a radiation boost to the supraclavicular region may bring clinical benefits. However, if the degree of dissection is high, a radiation boost to the supraclavicular region may not bring significant clinical benefits.
		2021 Vol. 30 (5): 462-467 [Abstract] ( 169 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Physics·Technique·Biology

	468	Different receptive fields-based automatic segmentation network for gross target volume and organs at risk of patients with nasopharyngeal carcinoma
		Liu Yuliang, Li Yongbao, Qi Mengke, Wu Aiqian, Lu Xingyu, Song Ting, Zhou Linghong
		Objective To establish an automatic segmentation network based on different receptive fields for gross target volume (GTV) and organs at risk in patients with nasopharyngeal carcinoma. Methods Radiotherapy data of 100 cases of nasopharyngeal carcinoma including CT images and GTV and organs at risk delineated by the physicians were collected. Ninety plans were randomly selected as the training dataset, and the other 10 plans as the validation dataset. Firstly, the images were subject to three data augmentation methods including center cropping, vertical flipping and rotation (-30°to 30°), and then input into MA_net networks proposed in this study for training. The model performance of networks was assessed by the number of network parameters (NP), floating-point number (FPN), the running memory (RM) and Dice index (DI), and eventually compared with DeeplabV3+, PSP_net, UNet++ and U_Net networks. Results When the input image was in the size of 240×240, MA_net had a NP of 23.20%, 20.10%, 25.55% and 27.11% of these 4 networks, 50.02%, 19.86%, 6.37% and 13.44% for the FPN, 40.63%, 23.60%, 11.58% and 14.99% for the RM, respectively. For the DI of GTV, MA_net was 1.16%, 2.28%, 1.27% and 3.59% higher than these 4 networks. For the average DI of GTV and OAR, MA_net was 0.16%, 1.37%, 0.30% and 0.97% higher than these 4 networks. Conclusion Compared with those four networks, the proposed MA_net network has slightly higher Dice index with fewer parameters, lower FPN and smaller RM.
		2021 Vol. 30 (5): 468-474 [Abstract] ( 264 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	475	Effect of different cone-beam CT image-guidance strategies on the accumulated dose of radiotherapy for spine metastases
		Jia Chenghao, Zhao Bo, Gao Xianshu, Zhang Min, Gao Yan, Liu Siwei, Shang Zhaocai, Li Yue, Liu Peilin
		Objective To evaluate the effect of setup errors from daily cone-beam computed tomography (CBCT) on the accumulated dose under different image-guidance (IG) strategies, aiming to investigate the appropriate IG strategies during radiotherapy for the spine metastases. Methods A total of 720 CBCT scans of 36 vertebral lesions were obtained. All 36 lesions were divided into the simultaneous boosting (PTV 40Gy/20f, GTV 60Gy/20f, n=20) and conventional radiotherapy groups (PTV 40Gy/20f, n=16). The actual fractionated plan was recalculated simulatively after transferring the isocenter of the initial plan according to the interfraction setup error. Under no daily image-guidance (no-DIG) strategies including twice imaging guidance weekly (TIG), initial 5 days then weekly imaging guidance (5D+WIG), WIG and no imaging guidance (NIG), the dose deviation was calculated between the delivered dose accumulated by each actual fractionated plan and the dose distribution under DIG. The tolerance of dose deviation for the target was within ±5% and the Dmax of the spinal cord was limited below 45Gy. Results Under different image-guidance strategies of TIG, 5D+WIG, WIG and NIG, the median dose deviation was approximately ±1% for the CTV D95% and Dmax of spinal cord. However, the median dose deviation wasbeyond-5% for the PTV D95% when conventional radiotherapy was given. The median dose deviation was approximately 10% for the Dmax of spinal cord and the proportion of cases whose maximum irradiated dose of spinal cord was more than 4500 cGy was ≥70%. Also, the median dose deviation was beyond -5% for the GTV D95% and PTV D95% when simultaneous boosting was delivered. Conclusions Because the dose deviation of CTVand spinal cord is within the tolerance limit, the image-guidance strategies could be chosen according to the clinical practice when conventional radiotherapy is delivered. However, the dose deviation of spinal cord, GTV and PTV exceeds the tolerance limit under no-DIG strategieswhen simultaneous boosting is delivered. Hence, it is necessary to perform daily IGRT for the spine metastases.
		2021 Vol. 30 (5): 475-480 [Abstract] ( 235 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	481	Kidney motion in each direction and influencing factors derived from four dimensional computed tomography under free-breathing condition
		Ma Mingwei, Gao Xianshu, Li Hongzhen, Zhao Bo, Zhang Min, Liu Siwei, Qin Shangbin, Qi Xin, Bai Yun
		Objective To explore the amplitude of normal kidney motion in the 3D direction and its influencing factors under free-breathing condition. Methods Clinical data of 28 patients with a KPS score≥80 who received 4D CT scan from March 2018 to March 2019 were collected. All patients were diagnosed with liver, pancreatic or lung tumors. The kidney was outlined and the geometric center and 3D coordinate values were recorded. The motion of bilateral kidneys in each direction and the 3D direction was calculated. The volume of kidney and surrounding organs, age, sex, height and body mass index (BMI) were recorded. Clinical data were statistically compared by t-test or nonparametric test. Results The motion of the left and right kidneys in the the sup-inf (SI) direction were the largest up to (8.39±3.18) mm and (7.71±3.55) mm. The motion amplitudes of bilateral kidneys in male patients were significantly larger than those of the female counterparts in the left-right (LR), SI and 3D directions (all P<0.05). The motion amplitudes of bilateral kidneys in patients taller than 165cm were significantly larger than those of their counterparts with a height of ≤165cm (all P<0.05). Patients with a BMI≥25kg/m²had significantly larger motion amplitudes of the left kidney in the LR and ant-post (AP) directions compared with those of normal weight counterparts (all P<0.05). The motion amplitude of the left kidney in the AP direction in patients with the left kidney volume of >180cm³ was significantly larger than that of patients with smaller left kidney volume (P=0.014). Age was not significantly associated with kidney motion in each direction (P>0.05). Conclusions Kidney motion mainly occurs in the SI direction. The kidney motion amplitudes in male and taller patients are larger. Special attention should be paid to the use of breath motion control device to decrease the normal tissue damage.
		2021 Vol. 30 (5): 481-485 [Abstract] ( 162 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	486	Research on 2D-3D registration method combining improved mutual information and image pyramid
		Qiu Yingchi, Yao Yunping, Zhang Peng
		Objective To evaluate the value of 2D-3D registration method which combines improved mutual information and image pyramid. Methods The continuous image representation of the cubic B-spline curve and Parzen histogram estimation were fused into the algorithm. The chest was used as the research object. The reconstruction of the orthogonal X-ray image generated by the radiographic image and the image after a certain transformation with itself were used for registration experiments to study the registration accuracy and time. Results After 50 sets of controlled experiments, compared with the traditional registration method, the displacement accuracy of this method in the X and Y directions was improved by 53.39% and 21.33%, and the registration time was shortened by 91.93%. Compared with the modified algorithms in recent years, the displacement accuracy of the improved algorithm in the X and Y directions was increased by 17.65% and 13.79%. And the registration time was further increased by 19.64%. Conclusions This method can effectively improve the registration accuracy and efficiency of 2D and 3D images, and both meet the requirements of image registration within 2 mm during surgery. The high efficiency and accuracy of this method provide beneficial information for clinical diagnosis and radiotherapy automation, which also lays the foundation for tumor position error correction and automatic positioning of medical robotic arms.
		2021 Vol. 30 (5): 486-491 [Abstract] ( 164 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	492	Sensitivity evaluation of ArcCheck in detecting leaf open time errors of helical tomotherapy delivery
		Yue Qi, Duan Jimei, Xiao Bin, Wang Zhiwei, Zhang Yue, Yang Xiumei, Gu Dan
		Objective To evaluate the sensitivity of the ArcCheck dosimetry system in detecting the leaf open time errors during the center and off-center helical tomotheray delivery quality assurance (DQA). Methods Nine nasopharyngeal carcinoma (NPC) patients were selected in this study. Two DQA plans were created for each patient:the"center" plan was created by moving the image of the ArcCheck phantom to place the high dose region on the phantom center and the "off-center" plan was created by offsetting the phantom and putting several diodes through a higher does region. Leaf open time errors of 2, 4, 6, 8 and 10 ms were introduced to the Sinogram which was modified using Matlab. Each intentional error plan and original (no error) plan for each patient were measured using both "center" and "off-center" DQA methods, the γ analysis was performed to evaluate the DQA results. The different dose and distance error criteria of 3%/3 mm,3%/2 mm and 2%/2 mm were selected, and different thresholds of 5%,10% and 15% were selected for γ analysis. The gradient and the minimum detectable error approach were taken to quantitatively analyze the sensitivity. The correlation between different dose distance error criteria and different thresholds was also evaluated by Pearson correlation analysis. Results The absolute value of γ gradient of the "center" DQA plans were larger than those of the "off-center" plans in all different γ criteria (all P<0.05). The stricter the γ criteria were adopted, the more sensitive DQA results of leaf open time error were obtained. The minimum detectable error was 2 ms in all different γ criteria for the "center" DQA plan. The minimum error detectability of the "off-center" DQA plan was weaker than that of the "center" DQA plan. The γ passing rates of three different dose distance error criteria were significantlystronglycorrelated for the "center" DQA plan (R²>0.9). For the "off-center " DQA plan, only the 3%/3 mm and 3%/2 mm criteria were significantlystrongly correlated (R²>0.9). Significantstrongcorrelation was observed in the γ passing rate at different thresholds between the "off-center" and "center" DQA plans. Conclusions The "center" DQA plan method is more sensitive than the "off-center" DQA plan method in all γ criteria, and the γ passing rates in different γ criteria are strongly correlated for the "center" DQA plan. The "center" DQA plan method is recommended.
		2021 Vol. 30 (5): 492-497 [Abstract] ( 162 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	498	Regulation of glutathione S-transferase P1 on the radiosensitivity of mouse Lewis lung cancer cells
		Liang Yanjie, Zhang Pei, Du Lehui, Ma Na, Lei Xiao, Han Yanan, Zhao Xinyao, Qu Baolin
		Objective To explore the regulatory effect of glutathione S-transferase P1(GSTP1) on the radiosensitivity of mouse Lewis lung cancer (LLC) cells. Methods GSTP1-shRNA lentivirus and negative control lentivirus were used to respectively infect the LLC cells, and stable transgenic strains were selected. Real-time PCR and Western blot were conducted to quantitatively measure the expression levels of GSTP1 mRNA and protein in the LLC cells to verify the knockdown effect. The cell counting kit-8(CCK-8) assay was used to detect cell viability after irradiation. The colony formation assay was utilized to assess the cell proliferation ability after irradiation. Flow cytometry was performed to assess the level of cell apoptosis after irradiation. The tumor-bearing mice were established and irradiated to detect the changes in the tumor volume after irradiation. TUNEL staining was employed to detect the level of tumor apoptosis after irradiation. Immunofluorescence was used to detect the number of CD⁺₄CD⁺₈ T cells in the tumor after irradiation. Results Real-time PCR and Western blot showed that after shRNA lentivirus interference, the expression levels of GSTP1 mRNA and protein were significantly down-regulated. Down-regulation of GSTP1 reduced cell viability and proliferation, and increased the rate of cell apoptosis after irradiation. The tumor volume of the tumor-bearing mice after irradiation in the GSTP1 knockdown group was significantly smaller than that in the NC group, whereas the tumor apoptosis rate was significantly higher and the number of infiltrating CD⁺₄CD⁺₈ T cells in the tumor was remarkably higher compared with those in the control group. Conclusion Knockdown of GSTP1 can significantly increase the radiosensitivity of LLC cells and enhance the infiltration of lymphocytes in tumor tissues.
		2021 Vol. 30 (5): 498-502 [Abstract] ( 260 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	503	Effect of KAT5/miR-210/TET2 pathway on radioresistance of anaplastic thyroid carcinoma
		Cai Shang, Xu Wenjing, Wei Xi, Xu Bo, Tian Ye
		Objective To investigate the effect and mechanism of lysine acetyltransferase 5(KAT5) on the radio-sensitivity of anaplastic thyroid carcinoma (ATC). Methods The expression levels of endogenous KAT5 in ATC and normal thyroid cells were detected by Western blot and qRT-PCR. The effect of KAT5 specific inhibitor NU9056 on the radio-sensitivity of human ATC cells and normal thyroid cells was evaluated by colony formation assay. TCGA database, JASPAR database, along with Western blot, microRNA sequencing, qRT-PCR and dual-luciferase reporter assay were conducted to unravel the underlying mechanism. Results The expression of endogenous KAT5 at the protein and mRNA levels in human ATC cells was significantly higher than that in normal thyroid cells. NU9056 could significantly enhance the radiosensitivity of human ATC cells to 8505C and CAL-62, whereas showed no sensitization effect on normal thyroid cell Nthy-ori 3-1. Knockdown of KAT5 and NU9056 both down-regulated the expression level of miR-210 in the TC cells, while NU9056 decreased the expression level of transcription factor c-Myc. The putative binding sites of c-Myc in the miR-210 promoter region were predicted, and transfection of c-Myc plasmid significantly enhanced the luciferase activity of miR-210 promoter. Elevated miR-210 level was associated with worse survival of patients with thyroid carcinoma. Down-regulated expression of miR-210 decreased the TET2 mRNA level, while inhibition of miR-210 increased the TET2 mRNA level. Conclusion The aberrantly-activated KAT5/miR-210/TET2 pathway probably causes the radioresistance of ATC, becoming a novel sensitizing target for ATC radiotherapy in clinical practice.
		2021 Vol. 30 (5): 503-508 [Abstract] ( 269 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	509	Effect of GTPBP4 silencing on radiosensitivity of EC9706 cells
		Zhang Cuihong, Lyu Xin, Fan Cai, Ma Bojing, Zhang Yi, Zhang Jianjun
		Objective To investigate the effect of GTPBP4 silencing by RNA interference on the radiosensitivity of esphageal cancer EC9706 cells line. Methods The expression data of GTPBP4 in esophageal cancer tissues was obtained from public Gene Expression Omnibus (GEO) database. Recombinant plasmid-mediated RNA interference (RNAi) was employed to transfect the esophageal cancer EC9706 cell to evaluate the influence of GTPBP4 silencing on the proliferation, apoptosis and radiosensitivity of esphageal cancer EC9706 cells. The expression levels of GTPBP4 mRNA and protein and apoptosis-associated proteins of Bax,cleaved caspase-9,cleaved caspase-3 and Bcl-2 were determined by qRT-PCR and Western blot. The cell proliferation was determined by MTT assay. The changes in cell apoptosis were detected AnnexinⅤ-FITC/PI double staining flow cytometry. The variations in radiosensitivity after radiation exposure were assessed by clone formation assay. Results The expression level of GTPBP4 in the esophageal cancer tissues was significantly higher than that in the normal adjacent esophageal tissues (P<0.001). qRT-PCR and Western blot demonstrated that the expression levels of GTPBP4 mRNA and protein in the GTPBP4-siRNA group were significantly lower than those in the blank and negative control groups (both P<0.001), suggesting that the plasmid was successfully transfected into the EC9706 cells. MTT assay indicated that the EC9706 cell proliferation rate was significantly inhibited (P<0.001). Flow cytometry found that the apoptosis rate was significantly increased in the GTPBP4-siRNA group (P<0.001). After GTPBP4 gene interference combined with radiotherapy, the cell sensitivity enhancement ratio was 1.716. The apoptosis rate of EC9706 cells was significantly increased in the GTPBP4-siRNA group (P<0.001). The expression levels of apoptosis-associated proteins including cleaved caspase-9, cleaved caspase-3 and Bax were significantly up-regulated, whereas that of Bcl-2 was significantly down-regulated in the EC9706 cells in the GTPBP4-siRNA group (P<0.001, P=0.001, P=0.001 and P=0.005). Conclusions GTPBP4 gene is highly expressed in human esophageal cancer tissues. RNAi technology can effectively inhibit the expression of GTPBP4 gene in the EC9706 cells, thereby suppressing cell proliferation, inducing cell apoptosis and enhancing the radiosensitivity of cells.
		2021 Vol. 30 (5): 509-513 [Abstract] ( 245 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Review Articles

	514	Clinical research progress on EGFR-TKI combined with pulmonary SBRT in advanced non-small cell lung cancer with EGFR-sensitive mutations
		Zhu Kuikui, Li Zhenyu, Zhang Sheng, Meng Rui, Wu Gang
		Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has become the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with EGFR-sensitive mutations. However, acquired resistance cannot be avoided during the targeted treatment of EGFR-TKI, which may lead to the progression of NSCLC. Among them, approximately 50% of patients present with primary lung lesions and/or initial metastastic lesion progression. As a major local treatment, radiation therapy plays an irreplaceable role in the management of patients with advanced cancer. Stereotactic body radiation therapy (SBRT), which is implemented with the Cyberknife, is the most advanced radiation therapy technology to better meet clinical needs. In recent years, based on the abovementioned patterns of tumor recurrence, the treatment mode of pulmonary-lesion SBRT combined with EGFR-TKI can improve the tumor-free survival in advanced NSCLC patients, which has attracted widespread attention. In this article, the clinical research progresses on this combined therapeutic strategy were reviewed.
		2021 Vol. 30 (5): 514-517 [Abstract] ( 158 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	518	The role and application prospect of cGAS-STING signaling pathway in tumor treatment
		Gao Yanping, Jiang Xueping, Liu Xingyu, Chen Jiarui, Gong Yan, Xie Conghua
		Novel cancer immunotherapy can treat tumors through regulating innate immunity and adaptive immune system. cGMP-AMP synthase (cGAS) is a key regulator of innate immune response to both exogenous and endogenous DNA. After recognizing the cytoplasmic DNA, cGAS produces the second messenger cyclic GMP-AMP (cGAMP), which subsequently combines with the adaptor STING (also known as MITA, MPYS and ERIS) to mediate innate immunity by inducing the production of type I interferons and inflammatory cytokines. Recent studies have revealed that the cGAS/STING signaling pathway can be activated by tumor-derived DNA and by-products of genomic instability and affect the incidence and development of tumors, which plays a critical role in the natural antitumor immunity across cancer types and immune checkpoint blockade therapy. In this article, current understanding of cGAS/STING signaling pathway in tumors was summarized,the pivotal role in tumor immunity and radiotherapy was highlighted, and the potential targeted or alternative therapy of this signaling pathway was reviewed.
		2021 Vol. 30 (5): 518-522 [Abstract] ( 342 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	523	Research progress on radiation-induced hypothyroidism in nasopharyngeal carcinoma
		Zhou Ling, Chen Jia, Tao Changjuan, Chen Ming, Yu Zhonghua, Chen Yuanyuan
		Hypothyroidism is a common complication in patients with nasopharyngeal carcinoma after radiotherapy, and its incidence is mainly associated with clinical factors, such as radiotherapy, chemotherapy, sex, age and clinical stage, etc. The normal tissue complication probability models of radiation-induced hypothyroidism can be established by using related factors, which can be employed to screen the high-risk patients. In this article, clinical factors related to radiation-induced hypothyroidism were summarized, aiming to prevent the early radiation-induced hypothyroidism, reduce the incidence of hypothyroidism and improve the quality of life of patients.
		2021 Vol. 30 (5): 523-526 [Abstract] ( 165 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	527	Research progress on the association between radiation-induced lung injury and ferroptosis
		Zheng Yuming, Jiang Mawei, Zheng Leizhen, Zhu Meiling
		Radiation-induced lung injury (RILI) is a common complication after radiotherapy for lung cancer and alternative thoracic malignant tumors, while ferroptosis is a regulated cell death triggered by iron-dependent membrane lipid peroxidation. In this article, the relationship between RILI and ferroptosis was investigated from oxidative damage induced by reactive oxygen species, antioxidant network and iron homeostasis regulated by nuclear factor erythroid 2-related factor 2(Nrf2) as well as transforming growth factor involved in the inflammatory response, aiming to mitigate or inhibit the occurrence of RILI through regulating ferroptosis, thereby improving clinical prognosis of patients undergoing radiotherapy.
		2021 Vol. 30 (5): 527-530 [Abstract] ( 242 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	531	Research progress on the role of microbiota in radiotherapy-induced injury
		Liu Jingli, Li Lan, Zhou Pengcheng, Yang Juan, Li Xiangrong, Qu Guangqiao
		Human microbiota is composed of bacteria, viruses, fungi and other microorganisms, which are distributed in the oral cavity, nasal cavity, intestine, vagina and skin, etc. Human microbiota plays a pivotal role in the metabolism, immunity, hormones and homeostasis of the host. It can protect the host and maintain the homeostasis, and provoke the incidence of inflammation and tumors. Microbiota has been found to modulate the efficacy and toxicity of chemotherapy and immunotherapy for certain types of tumors. Nevertheless, large-scale studies in the context of radiation therapy have not been performed. In this article, the relationship between the microbiota and the radiotherapy response and toxicity changes of cancer patients was summarized, aiming to develop the optimal treatment plan for patients, and provide evidence for the prevention and treatment of radiotherapy-induced injury.
		2021 Vol. 30 (5): 531-534 [Abstract] ( 152 ) [HTML 1KB] [ PDF 0KB] ( 0 )

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Cancer Hospital of Chinese
　Academy of Medical
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Chinese Journal of Lung
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