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.9 Published 2021-09-15

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

Investigation Research

	871	Investigation of the basic situation of radiotherapy in Xinjiang in 2020
		Liu Kai, Zhao Min, Wang Ruozheng
		Objective To investigate the application of radiotherapy and the basic situation of teaching and scientific research in Xinjiang. Methods A unified questionnaire was adopted, distributed and collected by mail, instant messaging software and telephone. The basic situation of all radiotherapy affiliations in the whole region was counted. Results The questionnaire coverage rate was 100% with a recovery rate of 100%. In 2020, 17 affiliations operated radiotherapy in Xinjiang, including 23 linear accelerators, 1 cobalt-60 therapeutic machine, 3 gamma knives, 6 post-installed therapeutic machines, 13 special analogue positioning machines, 46 treatment planning systems, and 103 sets of radiotherapy quality control equipment. It was estimated that the number of radiotherapy equipment for one million people in the whole region was approximately 0.84. In Xinjiang, 359 radiotherapy personnel were registered, including 220 physicians, 49 physicists and 90 technicians. A total of 1270 beds were available, with an average daily treatment volume of approximately 1255 person-times. From 2016 to 2021, 17 affiliations have undertaken 9 National Natural Science Foundation of China and 49 provincial and ministerial projects. Nineteen doctoral degrees and 87 master's degrees were accredited. These affiliations participated in the publication of 25 articles in Chinese Journal of Radiation Oncology, of which 18 were published as the first authors and/or corresponding authors. Conclusions The radiotherapy work in Xinjiang has developed rapidly in recent years, but there is still a certain gap with the national average level. At the same time, several problems still exist in the whole region, such as regional differences, unbalanced allocation of radiotherapy resources and scientific research and teaching resources, which need further improvement.
		2021 Vol. 30 (9): 871-875 [Abstract] ( 104 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Head and Neck Tumors

	876	Comparison between HyperArc and conventional VMAT approach for brain metastases
		Yang Bo, Yu Lang, Wang Zhiqun, Wang Bei, Li Wenbo, Zhang Jie, Wang Xingliu, Zhu Hao, Wang Xiaoshen, Lan Maoying, Zhu Feng, Zhang Zhen, Hu Ke, Zhang Fuquan, Qiu Jie
		Objective To compare the dosimetric parameters and plan complexity between newly-delicated HyperArc (HA) and conventional volumetric-modulated arc therapy (VMAT) in the treatment of brain metastases. Methods For 26 patients with brain metastases, HA, conventional coplanar (Cop) and non-coplanar (Non-cop) VMAT plans with a prescription dose of 9Gy 3fx or 6Gy 5fx were generated. The dosimetric parameters for planning target volume (PTV), RTOG conformity index (RTOG CI), Paddick CI, homogeneity index (HI), gradient index (GI), maximum dose (Dmax) of brainstem and dose-volume parameters of brain-PTV(V2Gy-V26Gy) were statisticaly compared among these three approaches. In addition, the monitor unit (MU) and the plan complexity parameters (including MCSv and AlPO) were statistically compared. Results To prevent missed targets during treatment, all plans were established with RTOG CI of greater than 1.1. For Paddick CI, HA provided significantly higher conformity (0.89±0.019) than Non-cop (0.87±0.036, P=0.001) and Cop (0.88±0.017, P=0.003) VMAT. For GI, the fastest dose fall-off was noted in HA (3.35±0.64), followed by conventional Non-cop VMAT of (3.70±0.80), and conventional Cop VMAT of (4.90±1.85)(all P<0.05). For the brainstem sparing, HA plan performed better than Non-cop plan[(604.14±531.61) cGy vs.(682.75±558.22) cGy, P<0.05)]. For normal brain tissue sparing, HA approach showed significant reduction than conventional Cop and Non-cop VMAT (both P<0.05). For MU, HA approach (2872.60 ± 566.93) was significantly lower than those of Non-cop VMAT (3771.28 ± 1022.38, P<0.05) and Cop VMAT (4494.08 ± 1323.09, P<0.05). In terms of plan complexity, the MCSv of Cop plan was the lowest, indicating that the complexity was the highest (P<0.05). The AlPO of HA was significantly higher than that of Non-cop VMAT (P<0.05), suggesting that the complexity of HA plan was lower (P<0.05). Conclusion For the treatment of brain metastases, HA provides better conformity, more rapid dose fall-off, better sparing of brainstem and normal brain tissues and less plan complexity compared with conventional VMAT.
		2021 Vol. 30 (9): 876-881 [Abstract] ( 129 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	882	The value of automatic segmentation of target volume and organs at risk for nasopharngeal carcinoma
		Liu Yang, Zhang Ye, Yi Junlin
		Objective To evaluate the application value of deep deconvolutional neural network (DDNN) model for automatic segmentation of target volume and organs at risk (OARs) in patients with nasopharngeal carcinoma (NPC). Methods Based on the CT images of 800 NPC patients,an end-to-end automatic segmentation model was established based on DDNN algorithm. Ten newly diagnosed with NPC were allocated into the test set. Using this DDNN model, 10 junior physicians contoured the region of interest (ROI) on 10 patients by using both manual contour (MC) and DDNN deep learning-assisted contour (DLAC) methods independently. The accuracy of ROI contouring was evaluated by using the DICE coefficient and mean distance to agreement (MDTA). The coefficient of variation (CV) and standard distance deviation (SDD) were rendered to measure the inter-observer variability or consistency. The time consumed for each of the two contouring methods was also compared. Results DICE values of gross target volume (GTV) and clinical target volume (CTV), MDTA of GTV and CTV by using DLAC were 0.67±0.15 and 0.841±0.032,(0.315±0.23)mm and (0.032±0.098)mm, respectively, which were significantly better than those in the MC group (all P<0.001). Except for the spinal cord, lens and mandible, DLAC improved the DICE values of the other OARs, in which mandible had the highest DICE value and optic chiasm had the lowest DICE value. Compared with the MC group, GTV, CTV, CV and SDD of OAR were significantly reduced (all P<0.001), and the total contouring time was significantly shortened by 63.7% in the DLAC group (P<0.001). Conclusion Compared with MC, DLAC is a promising method to obtain superior accuracy, consistency, and efficiency for the GTV, CTV and OAR in NPC patients.
		2021 Vol. 30 (9): 882-887 [Abstract] ( 114 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	888	Preliminary survival analysis of postoperative simultaneous radiochemotherapy with hyperthermia in glioblastoma patients
		Zhao Jingyi, Li Bingyan, Chen Linhui, Liang Tiansong, Zheng Yingjuan, Yang Daoke
		Objective To initially investigate whether simultaneous radiochemotherapy with hyperthermia can prolong the survival of glioblastoma (GBM) patients. Methods Clinical data of 61 GBM patients undergoing surgery in our hospital from September 2016 to June 2019 were retrospectively analyzed. According to different treatment methods, all patients were divided into the control group (n=34) and observation group (n=27). In the control group, three-dimensional radiotherapy with a dose of 60Gy combined with temoazolamine chemotherapy was delivered. In the observation group, simultaneous radiochemotherapy with 15-20 cycles of hyperthermia at 40-41℃ was supplemented. The survival time was calculated by Kaplan-Meier method, and the survival time was compared with log-rank test between two groups. Results The median progression-free survival in the observation group was significantly longer than that in the control group (14.33 months vs.9.94 months, P<0.05). The median overall survival in the observation group was also remarkably higher than that in the control group (18 months vs. 14 months, P<0.05). Conclusions Simultaneous radiochemotherapy with hyperthermia is innovatively applied to treat GBM after surgical resection. Preliminary findings demonstrate that compared with chemoradiotherapy, simultaneous radiochemotherapy with hyperthermia can prolong the survival time of GBM patients.
		2021 Vol. 30 (9): 888-891 [Abstract] ( 101 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Thoracic Tumors

	892	Efficacy and safety of salvage radiotherapy for recurrent esophageal cancer after chemoradiotherapy:a Meta-analysis
		Yu Wenhui, Zhang Ping, Zhen Chanjun, Bai Wenwen, Liu Sihan, Chen Mingyue, Zhou Zhiguo
		Objective To compare the efficacy and adverse events of salvage radiotherapy and other treatments for recurrent esophageal cancer after chemoradiotherapy in this Meta-analysis. Methods Databases including PubMed, Embase, Cochrane Library, CNKI and Wanfang data were searched from the inception to April 2020 to collect the clinical trials which comparatively analyzed the efficacy and safety between radiotherapy and other treatments for recurrent esophageal cancer after chemoradiotherapy. Meta-analysis was performed using RevMan 5.1 software. RR and 95%CI were used to describe the differences among different groups. Results According to the inclusion and exclusion criteria, a total of 11 clinical trials involving 842 patients were included. Meta-analysis showed that the overall survival in the salvage radiotherapy group was significantly lower than that in the salvage esophagectomy group (RR=0.40,95%CI:0.27-0.61,P<0.001), whereas significantly higher than that in the chemotherapy group (RR=2.91,95%CI:1.43-5.95,P=0.003). There was no significant difference in the treatment-related mortality between the salvage radiotherapy and salvage esophagectomy groups (RR=0.53,95%CI:0.14-1.98,P=0.350), but the incidence was significantly higher in the salvage esophagectomy group (1.7%-11.4% vs. 1.9%-2.8%). Conclusion Salvage radiotherapy is an effective treatment for recurrent esophageal cancer after chemoradiotherapy, which can be regarded as one choice for clinical patients.
		2021 Vol. 30 (9): 892-897 [Abstract] ( 120 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Abdominal Tumors

	898	Radiotherapy for and prognosis of breast cancer patients with isolated chest wall recurrence after mastectomy
		Xuan Liang, Zhao Xuran, Sun Huiru, Yin Jun, Tang Yu, Jing Hao, Fang Hui, Song Yongwen, Jin Jing, Liu Yueping, Ren Hua, Chen Bo, Qi Shunan, Li Ning, Tang Yuan, Lu Ningning, Yang Yong, Wu Shikai, Li Yexiong, Wang Shulian, Sun Bing
		Objective To investigate the radiation field and dose selection of patients with isolated chest wall recurrence (ICWR) after modified radical mastectomy, and analyze the prognostic factors related to subsequent chest wall recurrence. Methods Clinical data of 201 patients with ICWR after mastectomy admitted to the Fifth Medical Center, Chinese PLA General Hospital from 1998 to 2018 were retrospectively analyzed. None of the patients received postoperative adjuvant radiotherapy. After ICWR, 48 patients (73.6%) underwent surgery and 155 patients (77.1%) received radiotherapy. Kaplan-Meier method was used to calculate the post-recurrence progression-free survival (PFS) rates and the difference was compared by log-rank test. Multivariate analysis was performed using Cox regression model. Competing risk model was adopted to estimate the subsequent local recurrence (sLR) rates after ICWR and the difference was compared with Gray test. Multivariate analysis was conducted using F&G analysis. Results With a median follow up of 92.8 months after ICWR, the 5-year PFS rate was 23.2%, and the 5-year sLR rate was 35.7%. Multivariate analysis showed that patients with surgery plus radiotherapy and recurrence interval oF>12 months had a lower sLR rate. Patients with recurrence interval oF>48 months, local plus systemic treatment and surgery plus radiotherapy had a higher PFS rate. Among the 155 patients who received chest wall radiotherapy after ICWR, total chest wall irradiation plus local boost could improve the 5-year PFS rate compared with total chest wall irradiation alone (34.0% vs. 15.4%, P=0.004). Chest wall radiation dose (≤60Gy vs.>60Gy) exerted no significant effect upon the sLR and PFS rates (both P>0.05). In the 53 patients without surgery, the 5-year PFS rates were 9.1% and 20.5%(P=0.061) with tumor bed dose ≤60Gy and>60Gy, respectively. Conclusions Local radiotherapy is recommended for patients with ICWR after modified radical mastectomy of breast cancer, including total chest wall radiation plus local boost. The radiation dose for recurrence should be increased to 60Gy, and it should be above 60Gy for those who have not undergone surgical resection. In addition, patients with ICWR still have a high risk of sLR, and more effective treatments need to be explored.
		2021 Vol. 30 (9): 898-902 [Abstract] ( 183 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	903	Efficacy of prophylactic irradiation of internal mammary lymph nodes in breast cancer:a Meta-analysis
		Jia Sicong, Liu Zhikun, Zhang Jun, Zhao Chenguang, Zhu Longyu, Kong Jie, Han Huina, Shang Yuguang, Shen Dongxing, Duan Xuejuan
		Objective To evaluate the effect of prophylactic irradiation of internal mammary lymph nodes in patients with breast cancer in this Meta-analysis. Methods CNKI, Wanfang Medical network, CBM, PubMed, EMBASE and Web of Science were searched by computer. The controlled clinical studies comparing whether or not internal mammary lymph node irradiation as an intervention were included and the quality of the included literature was evaluated according to Newcastle-Ottawa Scale (NOS). RevMan 5.3 software and Stata 14 software were used for Meta-analysis. Results A total of 11 original articles were included, and 13181 patients were included for Meta-analysis. There was no statistically significant difference in the overall survival (OS) between patients with and without internal mammary lymph node irradiation (P=0.490). The subgroup analysis using the date of treatment and the degree of risk in the enrolled population as criteria showed that 5-year OS was significantly increased after internal mammary area irradiation in high-risk stage Ⅱ-Ⅲ patients (N+, T3-T4 stage) with the date of treatment of after 2000(P=0.003, 0.006). Compared with patients without internal mammary area irradiation, internal mammary irradiation significantly increased the 5-year disease-free survival (DFS)(P<0.001). Conclusion Under the modern radiotherapy technology, internal mammary lymph node irradiation improves the DFS of patients, and may bring OS benefits to high-risk stage Ⅱ-Ⅲ breast cancer patients (N+, T3-T4 stage).
		2021 Vol. 30 (9): 903-909 [Abstract] ( 128 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	910	The value of circulating miR-143 level in predicting early response to concurrent chemoradiotherapy in cervical cancer patients
		Chen Cuiyun, Wang Meiyun, Zhu Qingyao, Fu Fangfang, Li Xiaodong, Wen Zejun, Zhu Shaocheng, Liu Jie, Liang Feifei, Lian Lixia
		Objective To investigate the value of serum miR-143 level combined with MRI in predicting the early response to concurrent chemoradiotherapy (CCRT) in cervical cancer. Methods A total of 85 patients with pathologically confirmed cervical cancer underwent conventional MRI, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), and dynamic contrast-enhanced MRI (DCE-MRI) before CCRT. The biopsy tissues and serum samples were collected. The differential expression of miRNA in the biopsy tissues was determined by microarray chip. The expression level of miR-143 in the serum samples was analyzed by qRT-PCR. All patients were divided into the non-residual and residual tumor groups according to post-treatment MRI. Pre-treatment clinical factors, MRI parameters and miR-143 between two groups were statistically analyzed by the univariate and multivariate analyses. The optimal thresholds and predictive performance for post-treatment incidence of residual tumors were estimated by drawing the ROC curve. Results At one month after CCRT, there were 52 patients in the non-residual tumor group and 33 patients in the residual tumor group. In the residual tumor group, pre-treatment FIGO staging, apparent diffusion coefficient (ADC), D and V^e were significantly higher (all P<0.05), whereas K^trans value was significantly lower (P<0.001) when compared to those in the non-residual tumor group. The miRNA array analysis showed that there were 16 miRNAs with differential expression levels between two groups (all P<0.05). Among them, the increase of miR-143 was the most significant in the residual tumor group. Compared with the residual tumor group, the expression level of serum miR-143 was significantly down-regulated in the non-residual tumor group (P=0.002). Compared with the SiHa cells, the expression level of miR-143 in the SiHa-R cells was significantly up-regulated (P<0.05). Multivariate analysis showed that only miR-143, D, K^trans and V^e were the independent prognostic factors. The combination of multi-parametric MRI and miR-143 exhibited the highest predictive performance (AUC=0.975), with a sensitivity of 84.8% and a specificity of 96.2%. Conclusion The combination of multi-parametric MRI with miR-143 further improves the predictive performance for residual tumors after CCRT, which contributes to the personalized treatment of cervical cancer.
		2021 Vol. 30 (9): 910-916 [Abstract] ( 105 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Physics·Technique·Biology

	917	Application of a multi-task learning-based light-weight convolution neural network for the automatic segmentation of organs at risk in thorax
		Zhang Jie, Yang Yiwei, Shao Kainan, Bai Xue, Fang Min, Shan Guoping, Chen Ming
		Objective To evaluate the application of a multi-task learning-based light-weight convolution neural network (MTLW-CNN) for the automatic segmentation of organs at risk (OARs) in thorax. Methods MTLW-CNN consisted of several layers for sharing features and 3 branches for segmenting 3 OARs. 497 cases with thoracic tumors were collected. Among them, the computed tomography (CT) images encompassing lung, heart and spinal cord were included in this study. The corresponding contours delineated by experienced radiation oncologists were ground truth. All cases were randomly categorized into the training and validation set (n=300) and test set (n=197). By applying MTLW-CNN on the test set, the Dice similarity coefficients (DSCs) of 3 OARs,training and testing time and space complexity (S)were calculated and compared with those of Unet and DeepLabv3+. To evaluate the effect of multi-task learning on the generalization performance of the model, 3 single-task light-weight CNNs (STLW-CNNs) were built. Their structures were totally the same as the corresponding branches in MTLW-CNN. After using the same data and algorithm to train STLW-CNN, the DSCs were statistically compared with MTLW-CNN on the testing set. Results For MTLW-CNN, the averages (μ) of lung, heart and spinal cord DSCs were 0.954, 0.921 and 0.904, respectively. The differences of μ between MTLW-CNN and other two models (Unet and DeepLabv3+) were less than 0.020. The training and testing time of MTLW-CNN were 1/3 to 1/30 of that of Unet and DeepLabv3+. S of MTLW-CNN was 1/42 of that of Unet and 1/1220 of that of DeepLabv3+. The differences of μ and standard deviation (σ) of lung and heart between MTLW-CNN and STLW-CNN were approximately 0.005 and 0.002. The difference of μ of spinal cord was 0.001, but σ of STLW-CNN was 0.014higher than that of MTLW-CNN. Conclusions MTLW-CNN spends less time and space on high-precision automatic segmentation of thoracic OARs. It can improve the application efficiency and generalization performance of the models.
		2021 Vol. 30 (9): 917-923 [Abstract] ( 126 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	924	Dosimetric comparison of three techniques in radiotherapy for breast cancer after modified mastectomy
		Miao Junjie, Xu Yingjie, Zhai Yirui, Men Kuo, Wang Shulian, Dai Jianrong
		Objective To analyze and compare the dosimetric differences based on volumetric-modulated arc therapy (VMAT), fixed field intensity-modulated radiotherapy (F_IMRT), and electron irradiation combined with VMAT (E&VMAT) in radiotherapy for breast cancer after modified mastectomy, aiming to provide reference for clinical selection of treatment plan. Methods Ten patients with the left breast cancer who received radiotherapy after modified mastectomy were randomly selected. The target areas included chest wall and supraclavicular region, and the prescribed dose was 43.5Gy in 15 fractions (2.9Gy/F). Based on the Pinnacle³ planning system, the VMAT, F_IMRT and E&VMAT plans (electron beam for chest wall, VMAT for supraclavicular area) were designed for each patient. The conformity and homogeneity of the target areas, the dose of organs at risk and treatment time were compared. Results The VMAT plan could improve the dose distribution of the target areas. The conformity index and homogeneity index of the target dose were significantly better than those of the F_IMRT and E&VMAT plans (all P<0.05). The average dose, V30Gy, V20Gy, V10Gy of the left lung in the VMAT plan were significantly better than those in the F_IMRT and E&VMAT plans (all P<0.05). The V5Gy of the left lung in the VMAT plan was significantly better than that in the F_IMRT plan (P<0.05). There was no statistical difference in the V5Gy of the left lung between the VMAT and E&VMAT plans (P>0.05). The heart, right breast and right lung of the VMAT plan could meet the clinical dose limit requirements. The treatment time of the VMAT, F_IMRT and E&VMAT plans was (326±27) s,(1 082±169) s, and (562±48) s, respectively. Conclusions Compared with the F_IMRT and E&VMAT plans, the VMAT plan has better quality and shorter treatment time. VMAT plan has higher value in clinical application compared with the F_IMRT and E&VMAT plans.
		2021 Vol. 30 (9): 924-929 [Abstract] ( 115 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	930	Dosimetric effect of Varian high-definition multi-leaf collimator leaf position error on stereotactic body radiation therapy for lung tumors
		Zheng Jiajun, Zhai Zhenyu, Sun Li
		Objective To evaluate the effect of leaf position error of Varian high-definition multi-leaf collimator (HD120) on the dosimetry of stereotactic body radiation therapy (SBRT) for lung tumors. Methods Nine SBRT plans based on HD120 for lung tumors were selected as the reference plans. The parameters of the plans were modified by the in-house program based on the Varian Eclipse 15.6 scripting application program interface to generate the simulation plans with three types of leaf position errors including the isotropic systematic error, the anisotropic systematic error and the random error, respectively. Then, the dosimetric metric deviation between each simulation plan and the corresponding reference plan was calculated and regression analysis was performed to evaluate the dosimetric effect of three types of leaf position errors of HD120 on SBRT. Results The planning target volume (PTV) D99%, D2cm and V5Gy of double lungs were decreased quadraticly with the increase of the absolute value of the isotropic systematic error. The first-order sensitivity was -0.06%/mm to -0.26%/mm, and the second-order sensitivity was -0.55%/mm² to -1.17%/mm² (R²=0.96-0.99, P<0.01). The maximum change of PTV D99% was -3.13%. The linear regression analysis of the effects of the anisotropic systematic error and random error showed that the sensitivity of CI was 25.16%/mm (R²=0.98,P<0.01) and -4.84%/mm(R²=0.99, P<0.01), and the sensitivity of other dosimetric deviations with the anisotropic systematic error was 4.80%/mm to 5.12%/mm (R²=0.96-0.98, P<0.01), whereas the sensitivity with the random error was -0.47%/mm to -1.01%/mm (R²=0.96-0.99, P=0-0.02). Conclusions The dosimetric deviation of SBRT plan based on HD120 for lung cancer is highly sensitive to the anisotropic systematic error of leaf position, but less sensitive to the random error. In addition, the isotropic systematic error of leaf position will lead to the decrease of target coverage to a certain extent. Consequently, it is necessary to strictly control the systematic error of HD120 leaf position in the implementation of SBRT plan in clinical work.
		2021 Vol. 30 (9): 930-935 [Abstract] ( 136 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	936	Application of image similarity measure based on structure information and intuitionistic fuzzy set in radiotherapy setup verification
		Zhong Jiajian, Qiu Minmin, Huang Taiming, Xiao Zhenhua, Deng Yongjin
		Objective To propose a method of image similarity measurement based on structure information and intuitionistic fuzzy set and measure the similarity between CT image and CBCT image of radiotherapy plan positioning, aiming to objectively measure the setup errors. Methods A total of four pre-registration images of a nasopharyngeal carcinoma patient on the cross-sectional and sagittal planes and a pelvic tumor patient on the cross-sectional and coronal planes were randomly selected. Five methods were used to quantify the setup errors, including correlation coefficient, mean square error, image joint entropy, mutual information and similarity measure method. Results All five methods could describe the deviation to a certain extent. Compared with other methods, the similarity measure method showed a stronger upward trend with the increase of errors. After normalization, the results of five types of error increase on the cross-sectional plane of the nasopharyngeal carcinoma patient were 0.553, 0.683, 1.055, 1.995, 5.151, and 1.171, 1.618, 1.962, 1.790, 3.572 on the sagittal plane, respectively. The results of other methods were between 0 and 2 after normalization, and the results of different errors of the same method slightly changed. In addition, the method was more sensitive to the soft tissue errors. Conclusions The image similarity measurement method based on structure information and intuitionistic fuzzy set is more consistent with human eye perception than the existing evaluation methods. The errors between bone markers and soft tissues can be objectively quantified to certain extent. The soft tissue deviation reflected by the setup errors is of significance for individualized precision radiotherapy.
		2021 Vol. 30 (9): 936-941 [Abstract] ( 107 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	942	Preliminary study of the detection of genes related to sensitivity to concurrent chemoradiotherapy based on circulating free DNA in locally advanced esophageal squamous cell carcinoma
		Wang Xiaofeng, Liang Jun
		Objective To explore the genes and molecular markers related to the sensitivity to concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. Methods The peripheral blood sample of 31 patients with locally advanced esophageal squamous cell carcinoma receiving radical concurrent chemoradiotherapy was collected and the plasma circulating free DNA (cf-DNA) was extracted before treatment. The target gene capture sequencing technology based on NovaseQ6000high-throughput sequencing platform was employed to detect the changes of target genes and tumor mutation burden (TMB). According to the short-term efficacy of chemoradiotherapy, all patients were divided into the chemoradiotherapy-sensitive group (CR+PR) and chemoradiotherapy-resistant group (SD+PD). Bioinformatics and clinical data were adopted to analyze the differences of gene mutation and TMB between two groups. Results In the sequencing data of 31 patients, the tumor-related genes with a mutation frequency above 10% were Tp53, Notch1, BRAF, FGFR4, CDKN2A, ATRX and Axin2, which were almost equally distributed between the CR+PR and SD+PD groups. High-frequency mutant genes were associated with 7 signaling pathways, mainly involved in the RTK/RAS signaling pathways. The TMB value in the CR+PR group was higher than that in the SD+PD group (P=0.04), however, the mutation rate of GXYLT1 and KRT18 genes in the SD+PD group was higher than that in the CR+PR group (P<0.05). Conclusions Tp53, Notch1 and CDKN2A may be the high-frequency mutant genes associated with the incidence and progression of esophageal squamous cell carcinoma. KRT18, GXYLT1 and TMB are closely correlated with the sensitivity to concurrent chemoradiotherapy of patients with locally advanced esophageal squamous cell carcinoma.
		2021 Vol. 30 (9): 942-948 [Abstract] ( 106 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	949	Regulation and mechanism of Myosin X on radiosensitivity of non-small cell lung cancer cell line H1975 in vitro
		Shen Hui, Ou Haibin, Shao Jin, Jiang Yaofei, Liu Yu, Zhang Junhong, Xie Conghua
		Objective To investigate the effect and mechanism of Myosin X on the radiosensitivity of non-small cell lung cancer (NSCLC) cell line H1975 in vitro. Methods Western blot was applied to detect the expression level of Myosin X expression. The H1975 cell line with stable knockout of Myosin X (KO group) and infected with control virus (NC group) were constucted by using CRISPR/Cas9 technique. The knockout efficiency was validated. The radiosensitivity of two cell lines was measured by colony formation assay and single-hit multi-target model. γ-H2AX focus formation test and RNA sequencing (RNAseq) analysis were employed to identify the regulatory mechanism of the radiosensitivity of lung cancer cell lines mediated by Myosin X. Results The expression level of Myosin X in the H1975 cells was significantly up-regulated than those in other NSCLC cell lines (all P<0.01). The lentiviral vector of Myosin X sgRNA-Lenti-CRISPR v2 was successfully constructed. After the puromycin screening, H1975 cell lines with complete knockout of Myosin X and control cell lines (NC group) were obtained. Colony formation assay demonstrated that compared with the NC group, the radiosensitivity in the KO group was significantly higher (The D0 value was decreased from 1.28Gy to 1.03Gy, SF2decreased from 0.29 to 0.21, and the sensitization ratio was 1.24). The γ-H2AX focus formation test showed that the number of damage focus formed at 1h and 6h after irradiation in the KO group was significantly larger than that in the NC group (P<0.05. RNAseq analysis indicated that the expression level of ISLR in the KO group was significantly down-regulated than that IN the NC group (P<0.05). Conclusion Knockout of Myosin X can increase the radiosensitivity of H1975 cells probably by interfering the repair of DNA double-strand damage and down-regulating the expression level of ISLR.
		2021 Vol. 30 (9): 949-955 [Abstract] ( 123 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	956	Effect of resveratrol combined with radiotherapy on cervical cancer Hela cell growth and migration by regulating PI3K/Akt/mTOR signaling pathway
		Zhang Jianfu, Zhang Yunjun, Jiang Bengui, Mei Haibing, Zhong Huizhen
		Objective To evaluate the effect of resveratrol combined with γ-ray irradiation on the biological behavior of cervical cancer cells, and to explore its possible mechanism. Methods The proliferation of cell populations after different concentrations of resveratrol solution±γ-ray irradiation was detected by CCK-8 assay. Scratch test and Transwell chamber test were used to detect cell migration and invasion. Flow cytometry and Annexin V-FITC/PI double staining were employed to assess cell apoptosis. Western blot was performed to measure the expression levels of PI3K, Akt, p-Akt, mTOR and p-mTOR proteins. Results Compared with the normal control (NC) group, the resveratrol group±γ-ray irradiation could inhibit the proliferation, migration, and invasion and promote cell apoptosis of human cervical cancer Hela cells, and the combined effect was more obvious. Compared with the NC group, resveratrol and γ-ray irradiation could significantly down-regulate the expression levels of Bcl-2, PI3K, p-Akt and p-mTOR proteins, up-regulate the expression level of Bax protein, but did not significantly alter the expression levels of Akt and mTOR proteins in human cervic1255al cancer Hela cells. Conclusions Resveratrol combined with γ-ray irradiation can dramatically inhibit the proliferation, migration, invasion, and promote the apoptosis of cervical cancer Hela cells. The mechanism may be related to the inhibition of the PI3K/Akt/mTOR signaling pathway and down-regulating the expression levels of downstream related proteins.
		2021 Vol. 30 (9): 956-960 [Abstract] ( 95 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	961	Effect of circ_0001955 targeted regulation of miR-149 on the radiosensitivity of prostate cancer DU145 cells
		Li Zheng, Zhang Tianbiao, Cheng Shuanglei, Wu Xiaoyuan
		Objective To investigate the effect and molecular mechanism of circ_0001955 on the radiosensitivity of prostate cancer DU145 cells. Methods The si-con, si-circ_0001955, miR-con and miR-149 were transfected into DU145 cells and recorded as the si-con group, si-circ_0001955 group, miR-con group, miR-149 group. The miR-149 and pc-circ_0001955 were co-transfected into DU145 cells and recorded as the miR-149+pc-circ_0001955 group. Untreated cells were used as the blank control (NC) group. Real-time quantitative PCR was employed to detect the expression levels of circ_0001955 and miR-149. MTT assay was performed to detect cell viability. Flow cytometry was carried out to detect cell apoptosis. Transwell chamber assay was conducted to observe cell migration and invasion. Western blot was performed to detect the expression levels of MMP-2, MMP-9, Cleaved caspase-3, Cleaved caspase-9 and γ-H2AX proteins. Colony formation assay was employed to determine the cell radiosensitivity. Dual-luciferase reporter assay was conducted to verify the targeting relationship between circ_0001955 and miR-149. Results The circ_0001955 was highly expressed, whereas the miR-149 was lowly expressed in prostate cancer DU145 cells. Silencing circ_0001955 or over-expressing miR-149 could decrease the cell viability, migration and invasion, down-regulate the expression levels of MMP-2 and MMP-9, up-regulate the expression levels of Cleaved caspase-3 and Cleaved caspase-9, and increase the apoptosis rate (all P<0.05). After 4Gy dose irradiation, the expression level of γ-H2AX was up-regulated, the cell survival fraction was decreased, and the sensitivity ratio was 1.38. circ_0001955 could targetedly regulate the expression level of miR-149. After simultaneous overexpression of circ_0001955 and miR-149, cell proliferation activity and the number of migrating and invading cells were increased, cell apoptosis rate was decreased, and cell survival fraction was increased, and the sensitivity ratio was calculated as 0.72. Conclusion Silencing circ_0001955 can targetedly up-regulate the expression level of miR-149, which inhibits the proliferation, migration, and invasion, induces cell cycle arrest, induces cell apoptosis and increases the radiosensitivity of prostate cancer DU145 cells.
		2021 Vol. 30 (9): 961-967 [Abstract] ( 108 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Review Articles

	968	Proton FLASH radiotherapy
		Huang Xin, Zhang Guoliang, Zhang Chunli, Jin Jing, Wang Lyuhua, Peng Hao
		FLASH radiotherapy (FLASH-RT) is a treatment modality that delivers ultra-high dose rate and ultra-fast radiation for cancer treatment. Compared to conventional dose rate radiotherapy, FLASH-RT can yield similar efficacy for tumors and achieve normal tissue protection, translating to an increased therapeutic window. Due to this unique feature, FLASH-RT is attracting increasing attention from the radiotherapy community, both academia and industry. Due to its unique Bragg peak as well as intrinsic high dose rate, application of FLASH has more value and profound significance in proton therapy while achieving highly conformal dose deposition simultaneously. This article reviews research progress on FLASH-RT, relevant cell and animal studies, experimental conditions and results. Moreover, this article also investigates the potential biological mechanisms, technical challenges for implementation and potential clinical applications of FLASH-RT.
		2021 Vol. 30 (9): 968-974 [Abstract] ( 200 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	975	Research progress on combined treatment of radiotherapy and anti-CTLA-4 antibody
		Zhang Zhiyuan, Xia Fan, Zhang Zhen
		Radiotherapy (RT) is one of the three prevailing therapeutics for tumors. With rapid development of immunotherapy (IM), the combination of IM and RT has gainned increasingly widespread attention. Cytotoxic T lymphocyte associated protein-4(CTLA-4) inhibitor is an important checkpoint target in immune activation and regulation, which exerts significant anti-tumor effects in melanoma and non-small cell lung cancer, etc. Accordingly, the combination of RT and anti-CTLA-4 antibody has become a hot spot. This article reviews research progress on pre-clinical and clinical evidences of RT combined with anti-CTLA-4 antibody, which provides evidence for further exploration in this field.
		2021 Vol. 30 (9): 975-978 [Abstract] ( 124 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	979	Current status and prospects of treatment of newly-diagnosed nasopharyngeal carcinoma with distant metastasis
		Ni Mengshan, Ying Hongmei
		From synchronous metastasis to metachronous metastasis and from oligometastasis to disseminated metastasis, distant metastatic nasopharyngeal carcinoma (stage IVB) has great heterogeneity. The prognosis of stage IVB nasopharyngeal carcinoma patients with distant metastases is closely related to the anatomical characteristics of metastases. Therefore, it is necessary to subdivide M1 stage to lay the foundation for individualized treatment of patients with metastatic nasopharyngeal carcinoma. In addition to systemic chemotherapy, the primary tumors and metastatic lesions should be considered during the treatment of newly-diagnosed metastatic nasopharyngeal carcinoma. Currently, there is a lack of recognized treatment modes for newly-diagnosed stageⅣB nasopharyngeal carcinoma, and more studies are needed to evaluate the clinical benefits of different treatment methods.
		2021 Vol. 30 (9): 979-983 [Abstract] ( 113 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	984	Research progress on application of radiotherapy to sensitize PD-1/PD-L1 inhibitors
		Kong Yuehong, Ma Yifu, Zhao Xiangrong, Zhang Liyuan
		Programmed cell death-1/programmed cell death-ligand 1(PD-1/PD-L1) inhibitors have been approved for a variety of tumors, whereas the efficacy as monotherapy is low. How to sensitize the efficacy of PD-1/PD-L1 inhibitors through combined radiotherapy is the current research focus. Multiple studies have demonstrated that the combination of radiotherapy and anti-PD-1/PD-L1 therapy has yielded survival benefits. Nevertheless, ionizing radiation is a double-edged sword for anti-PD-1/PD-L1 therapy. For patients with metastatic cancers, radiotherapy should be fully exerted as a sensitizer to systemic anti-PD-1/PD-L1 therapy and the immunosuppressive effects should be avoided as much as possible. It is closely correlated with the selection of radiation dose, fraction size, treatment timing and irradiated numbers and sites. Therefore, this article reviews how to optimize radiotherapy combined with anti-PD-1/PD-L1 treatment scheduled for advanced stage metastatic cancers.
		2021 Vol. 30 (9): 984-988 [Abstract] ( 90 ) [HTML 1KB] [ PDF 0KB] ( 0 )

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