Chinese Journal of Radiation Oncology

中华放射肿瘤学杂志

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Chinese Journal of Radiation Oncology

	2023 Vol.32 Issue.8 Published 2023-08-15

	Thoracic Tumors Review Articles Abdominal tumor Guideline Physics·Technique·Biology Head and Neck Tumor

Guideline

	665	Quality assurance guideline of radiotherapy treatment planning system for high energy photon external beam irradiation
		National Cancer Center / National Cancer Quality Control Center
		The radiotherapy treatment planning system (RTPS) is one of the core equipment used in implementing radiotherapy. With the advancement of radiotherapy technology, the functionality of the RTPS has become increasingly complex. According to the reports from the International Atomic Energy Agency (IAEA) regarding errors and accidents in radiotherapy, a significant proportion of them are caused by inadequate quality assurance or improper use of the RTPS. The quality assurance of the radiotherapy RTPS is the responsibility of medical physicists, which is essential for ensuring the safety and quality of radiotherapy. This guideline primarily provides guidance to medical physicists in carrying out their work and fulfilling their responsibilities. The content of the guideline covers the requirements on institutions, organizations, personnel involved in the quality assurance of the RTPS, and equipment, acceptance testing, commissioning, routine quality assurance of the RTPS, as well as general requirements for system management and safety. It is recommended that each institution refers to this guideline and develops its own programs for quality assurance practices of the radiotherapy RTPS to ensure proper application.
		2023 Vol. 32 (8): 665-674 [Abstract] ( 111 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Head and Neck Tumor

	675	The feasibility of individualized primary CTV for lateralized nasopharyngeal carcinoma
		Zhang Siyu, Huang Wenxuan, Wang Lijun, Liu Juying, Zhao Lijun, Wu Lirong, Wang Dejun, Xu Wenjing, Guo Yesong, Yan Pengwei, Zhang Lanfang, Zhai Zhenyu, Huang Shengfu, Hexia
		Objective To investigate the feasibility of individualized primary clinical target volume (CTV) delineation in intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC). Methods Clinical data of 87 consecutive patients newly diagnosed with lateralized NPC in Jiangsu Cancer Hospital between October 2016 and February 2018 were retrospectively analyzed. Lateralized NPC is defined as tumor invasion not exceeding the contralateral wall. According to the tumor spread, the primary CTV was optimized as follows: CTV2 only covered the medial part of the contralateral pterygopalatine fossa, whereas the contralateral foramen oval was not included; on the level of parapharyngeal space, the contralateral side of CTV only covered the posterior lateral lymph nodes, whereas the contralateral internal jugular vein was not regularly covered. Failure patterns and 5-year survival [local control rate (LCR), progression-free survival (PFS) and overall survival (OS)] were evaluated by Kaplan-Meier method. Paired t-test and rank-sum test were used to analyze the dose variation in the optimized region and adverse reactions. Results The median follow-up time was 59.5 months. The 5-year LCR, PFS, and OS were 98.9%, 86.5% and 92.1%, respectively. There was no local recurrence in the optimized area of CTV. Dosimetric comparison results showed that the doses of parotid gland, temporal lobe, cochlea and middle ear on the contralateral side were reduced by 13.45%, 9.14%, 38.83%, and 29.36%, respectively. Four cases (4.6%) developed grade 3 hearing loss, all on the ipsilateral side. The optimized scheme significantly alleviated the hearing loss on the contralateral side compared to that on the ipsilateral side (P<0.001). Other grade 3 late adverse reactions included cranial nerve injury, subcutaneous fibrosis in the neck and visual impairment, with 1 case each. Conclusion Individualized primary CTV for lateralized NPC is feasible and safe, with obvious dosimetric advantages and reduced adverse reaction rate, which is worthy of clinical promotion.
		2023 Vol. 32 (8): 675-682 [Abstract] ( 107 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Thoracic Tumors

	683	Analysis of failure patterns and survival after SBRT for 147 cases of T_1-2N₀M₀stage non-small cell lung cancer
		Wang Lin, Wang Ruiqi, Dong Baiqiang, Hu Xiao, Ma Honglian, Wang Zhun, Lai Xiaojing, Feng Wei, Lin Xiao, Jiang Youhua, Wang Changchun, Zhao Qiang, Jiang Haitao, Li Pu, Du Xianghui, Chen Ming, Chen Qixun, Xu Yujin
		Objective To analyze the failure patterns and survival after stereotactic body radiotherapy (SBRT) in patients with T_1-2N₀M₀ non-small cell lung carcinoma (NSCLC). Methods Clinical data of early-stage NSCLC patients who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary observed endpoint was the pattern of disease progression, which was divided into intra-field recurrence, regional lymph node recurrence and distant metastasis. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox's model. Results A total of 147 patients with 156 lesions were included. The median follow-up time was 44.0 months (16.5-95.5 months). A total of 57 patients (38.8%) progressed: 14 patients (24.5%) had recurrence with the 1-, 3-, and 5-year local recurrence rates of 2.0%, 10.9%, and 14.3%, respectively; 36 patients (63.2%) had Distant metastasis with the 1-, 3- and 5-year distant metastasis rates of 12.2%, 22.4% and 28.6%, respectively; and 7 patients (12.3%) had recurrence complicated with distant metastasis. The 3-, 5- and 7-year OS rates were 80.5%, 64.2% and 49.9% for all patients, respectively. The median OS was 78.4 months. The 3-, 5- and 7-year PFS rates were 64.8%,49.5% and 41.5%, with a median PFS of 57.9 months (95%CI: 42.3-73.5 months). Univariate and multivariate analyses showed that biologically equivalent dose and age were the factors affecting the efficacy of SBRT (both P<0.05). Conclusion Distant metastasis is the main failure pattern in patients with T_1-2N₀M₀ NSCLC after SBRT. High-risk population should be selected for further systematic treatment to improve the efficacy.
		2023 Vol. 32 (8): 683-688 [Abstract] ( 107 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	689	Prognostic value of pre-treatment prognostic nutrition index in patients with cervical and thoracic upper esophageal squamous cell carcinoma and radiation induced esophagitis
		Li Shuguang, Chen Junqiang, Li Youmei, Guo Xuehan, Deng Wenzhao, Wang Xiaobin, Zhu Shuchai, Shen Wenbin
		Objective To investigate the prognostic value of Onodera's prognostic nutrition index (PNI) before treatment in patients with cervical and upper thoracic esophageal squamous cell carcinoma (CUTESCC) undergoing definitive chemoradiotherapy (dCRT) and its predictive value in the occurrence of ≥ grade 2 radiation esophagitis (RE). Methods The data of 163 CUTESCC patients eligible for inclusion criteria admitted to the Fourth Hospital of Hebei Medical University from January 2012 to December 2017 were retrospectively analyzed. The receiver operating characteristic (ROC) curve was used to calculate the best cut-off value of PNI for predicting the prognosis of patients. The prognosis of patients was analyzed by univariate and Cox multivariate analyses. Logistics binary regression model was adopted to analyze the risk factors of ≥ grade 2 RE in univariate and multivariate analyses. The significant factors in logistic multivariate analysis were used to construct nomogram for predicting ≥ grade 2 RE. Results The optimal cut-off value of PNI was 48.57 [area under the curve (AUC): 0.653, P<0.001]. The median overall survival (OS) and progression-free survival (PFS) were 26.1 and 19.4 months, respectively. The OS (χ²=6.900, P=0.009) and PFS (χ²=9.902, P=0.003) of patients in the PNI ≥ 48.57 group (n=47) were significantly better than those in the PNI < 48.57 group (n=116). Cox multivariate analysis showed that cTNM stage and PNI were the independent predictors of OS (HR=1.513, 95%CI: 1.193-1.920, P=0.001; HR=1.807, 95%CI: 1.164-2.807, P=0.008) and PFS (HR=1.595, 95%CI: 1.247-2.039, P<0.001; HR=2.260, 95%CI: 1.439-3.550, P<0.001). Short-term efficacy was another independent index affecting PFS (HR=2.072, 95%CI: 1.072-4.003, P=0.030). Logistic multivariate analysis showed that the maximum transverse diameter of the lesion (OR=3.026, 95%CI: 1.266-7.229, P=0.013), gross tumor volume (GTV) (OR=3.456, 95%CI: 1.373-8.699, P=0.008), prescription dose (OR=3.124, 95%CI: 1.346-7.246, P=0.009) and PNI (OR=2.072, 95%CI: 1.072-4.003, P=0.030) were the independent factors affecting the occurrence of ≥ grade 2 RE. These four indicators were included in the nomogram model, and ROC curve analysis showed that the model could properly predict the occurrence of ≥ grade 2 RE (AUC=0.686, 95%CI: 0.585-0.787). The calibration curve indicated that the actually observed values were in good agreement with the predicted RE. Decision curve analysis (DCA) demonstrated satisfactory nomogram positive net returns in most threshold probabilities. Conclusions PNI before treatment is an independent prognostic factor for patients with CUTESCC who received definitive chemoradiotherapy. The maximum transverse diameter of the lesion, GTV, prescription dose and PNI are the risk factors for ≥ grade 2 RE in this cohort. Establishing a prediction model including these factors has greater predictive value.
		2023 Vol. 32 (8): 689-696 [Abstract] ( 85 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Abdominal Tumor

	697	CT radiomics model for predicting progression-free survival of locally advanced cervical cancer after concurrent chemoradiotherapy
		Liu Huiling, Cui Yongbin, Chang Cheng, Qiu Qingtao, Yin Yong, Wang Ruozheng
		Objective To construct machine learning models based on CT imaging and clinical parameters for predicting progression-free survival (PFS) of locally advanced cervical cancer (LACC) patients after concurrent chemoradiotherapy (CCRT). Methods Clinical data of 167 LACC patients treated with CCRT at Shandong Cancer Hospital from September 2015 to October 2021 were retrospectively analyzed. All patients were randomly divided into the training and validation cohorts according to the ratio of 7 vs. 3. Clinical features were selected by univariate and multivariate Cox proportional hazards model (P<0.1). Radiomics models and nomograms were constructed by radiomics features which were selected by least absolute shrinkage and selection operator (LASSO) Cox regression model to predict the 1-, 3- and 5-year PFS. Combined models and nomogram models were developed by selected clinical and radiomics features. The Kaplan Meier-curve, receiver operating characteristic (ROC) curve, C-index and calibration curve were used to evaluate the model performance. Results A total of 1 409 radiomics features were extracted based on the region of interest (ROI) in CT images. CT radiomics models showed better performance for predicting 1-, 3-and 5-year PFS than the clinical model in the training and validation cohorts. The combined model displayed the optimal performance in predicting 1-, 3-and 5-year PFS in the training cohort [area under the curve (AUC): 0.760, 0.648, 0.661, C-index: 0.740, 0.667, 0.709] and verification cohort (AUC: 0.763, 0.677, 0.648, C-index: 0.748, 0.668, 0.678). Conclusions Combined model constructed based on CT radiomics and clinical features yield better prediction performance than that based on radiomics or clinical features alone. As an objective image analysis approach, it possesses high prediction efficiency for PFS of LACC patients after CCRT, which can provide reference for clinical decision-making.
		2023 Vol. 32 (8): 697-703 [Abstract] ( 89 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Physics·Technique·Biology

	704	Dose reconstruction of volumetric modulated arc therapy for nasopharyngeal carcinoma based on log files and CBCT
		Zhu Xiang, Liu Hongyuan, Nie Xin, Yang Zhiyong, Liang Zhiwen, Liu Gang, Quan Hong
		Objective To reconstruct the dose of nasopharyngeal carcinoma and verify the results of the whole-process radiotherapy plan based on log files and cone beam CT (CBCT). Methods A total of 15 patients with nasopharyngeal carcinoma who received volumetric modulated arc therapy (VMAT) with Halcyon accelerator in the Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from February to September 2022 were retrospectively selected. Log files and CBCT for all fractionated radiotherapy were recorded. The errors of monitor unit (MU), gantry angle, and multi-leaf collimator (MLC) leaf position per control point were analyzed. The adaptive CT (aCT) were generated according to CBCT and planned CT (pCT) using a commercial software Velocity^TM, and the similarities among aCT, pCT and CBCT were analyzed. The original plan was modified from the log files and imported into the treatment planning system to calculate the delivered dose on the corresponding fractionated aCT to reconstruct the fractionated dose. And all the reconstructed doses were mapped back to pCT to obtain the cumulative dose. Theγpass ratios with criteria of 2 mm/2% and 2 mm/3% and the dose differences between the planned dose and the cumulative dose in the planning target volume (PTV) and organs at risk (OAR) were compared. Results The root mean square (RMS) and the 95th percentile of the errors of MU, gantry angle and MLC leaf position errors were within an acceptable range. The aCT generated by Velocity^TM had the anatomical structure of CBCT and the resolution, contrast, noise characteristics of pCT, which could be directly used for dose calculation. Compared with the planned dose, the changes of V_{70 Gy} of nasopharyngeal primary tumor (PTV_nx), V_{68 Gy} of cervical glands (PTV_nd) and V_{60 Gy} of planning target volume (PTV1) were -0.88%±1.91%, -2.99%±2.99% and -0.63%±0.93%, respectively, and V_{40 Gy} of parotid gland was increased to 2.65%±2.63%. Cumulative dose showed different degrees of PTV dose decrease (P<0.05) and parotid dose was increased (P<0.05). The γ pass ratio (2 mm/3%) between the cumulative dose and planned dose was 97.3%±2.7% and >95.0% in 86.7% of patients. Conclusions Based on the log files and CBCT, the whole-process dose reconstruction of nasopharyngeal carcinoma patients can be carried out. According to the results of dose reconstruction, the radiotherapy effect of the target area and OAR can be quantitatively evaluated. In the case of high dose coverage and conformity of the original plan, the reconstruction results show that the cumulative dose coverage of the target area is decreased, whereas that of the parotid gland is increased.
		2023 Vol. 32 (8): 704-710 [Abstract] ( 88 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	711	Effect of dwell time deviation constraint on the three-dimensional brachytherapy plans for cervical cancer
		Cao Ying, Yang Zhen, Tang Du, Yang Xiaoyu
		Objective To investigate the effect of dwell time deviation constraint of inverse optimization on the quality and position error robustness of three-dimensional (3D) brachytherapy plans for cervical cancer. Methods A total of 20 patients with cervical cancer receiving 3D brachytherapy treatment in Xiangya Hospital Central South University from August 2020 to August 2021 were retrospectively selected. All plans were designed using the Eclipse treatment planning system, and the dwell time deviation constraint parameter smooth value in the system were set to 0.00, 0.25, 0.50, 0.75, and 1.00, respectively. An inverse dose volume optimization algorithm was used to generate plans with various smooth values, and the optimization conditions were the same as the original clinical plans. Key dosimetric metrics and total dwell time differences were comparatively analyzed. The applicators were intentionally subjected to position errors (0.2-1.0 cm) in 6 directions (left-right, anterior-posterior, head-foot), and the effect of various smooth values on plan quality and robustness was assessed. There were 133 plans per case and 2 660 plans for 20 patients. The results were statistically analyzed using the Wilcoxon signed-rank nonparametric test. Results As the smooth value was increased, the modulation factor was gradually decreased and the D_{2 cm3} of the bladder and rectum was increased. Plans with smooth values of 0.25, 0.50, 0.75, 1.00 had modulation factors of 0.72±0.09, 0.63±0.08, 0.55±0.08, 0.51±0.06, respectively, lower than 0.75±0.05 of the plan with the smooth value of 0.00, and all differences were statistically significant (P=0.004, 0.002, 0.002, 0.002). The bladder D_{2 cm3} of plans with smooth values of 0.50, 0.75, 1.00 were (475.4±41.0) cGy, (483.7±46.2) cGy, and (489.0±46.8) cGy, respectively, higher than (469.8±41.8) cGy of the plan with the smooth value of 0.00, with statistically significant differences (all P=0.002). The rectum D_{2 cm3} of plans with smooth values of 0.50 and 0.75 plans were (413.2±93.3) cGy and (418.6±96.4) cGy, both higher than (410.2±91.5) cGy of the plan with the smooth value of 0.00, with statistically significant differences (P=0.006, 0.010). When positional errors were introduced, the high risk clinical target volume (HR-CTV) D_90%was close for different smooth plans at most positional errors, and the differences were not statistically significant. The organs at risk D_{2 cm3} of plans with the smooth value of 0.00 was lower than those of plans with other smooth values, and for the bladder and rectum, the differences were statistically significant at most positional errors (all P<0.01). Conclusions The dwell time deviation constraint parameter exerts significant effect on the plan quality, and the smaller the value of the constraint parameter, the higher quality of the plan. The dwell time deviation constraint parameter has slight impact on the positional error robustness of dosimetric indices of targets and key organs at risk.
		2023 Vol. 32 (8): 711-718 [Abstract] ( 94 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	719	Effects of niraparib on the radiosensitivity of human esophageal cancer cells and its mechanism
		Zhao Fuzhen, Feng Yue, Ma Zhaoming, Hu Lijun, Sun Fei, Wang Jianlin, Yu Jingping
		Objective To evaluate the effect of niraparib, the poly (ADP-ribose) polymerase (PARP) inhibitor, on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) and to preliminarily investigate its mechanism. Methods Human esophageal squamous cell carcinoma cells ECA-109 and KYSE-150 were divided into the control, niraparib, single irradiation, combined (niraparib+irradiation) groups. Cell proliferation was measured by CCK-8 assay. The changes of cell survival rate were detected by colony formation assay. The changes of cell cycle and apoptosis were analyzed by flow cytometry. The number of γH2AX foci was detected by immunofluorescence, and the expression levels of PARP-1, cleaved-PARP, RAD51, mitogen-activated protein kinase (MAPK) [extracellular signal-regulated kinase 1 and 2 (ERK1/2) ] and p-MAPK (ERK1/2) proteins were determined by Western blot. All data were expressed as Mean±SD. Data between two groups conforming to normal distribution through the normality test were subject to independent sample t-test and multiple groups were analyzed using one-way ANOVA. Results In human ESCC cells ECA-109 and KYSE-150, the proliferation of ESCC cells was significantly inhibited by niraparib combined with irradiation, and the values of average lethal dose (D₀), quasi-threshould dose(D_q), survival fraction after 2 Gy irradiation (SF₂) in the combined group were decreased compared with those in the single irradiation group. The effect of irradiation alone on apoptosis of ECA-109 and KYSE-150 cells was limited. Compared to single irradiation group, irradiation combined with niraparib further increased the apoptosis rate in ESCC cells (P=0.015, P=0.006). In ECA-109 cells, G₂/M phase arrest was significantly increased in combined group compared with irradiation alone group (P<0.001). In ECA-109 cells, the number of γH2AX foci in combined group was higher than that in the single irradiation group after 2 h, and showed a significantly slower decay of γH2AX foci (P<0.001). Moreover, niraparib combined with irradiation enhanced the radiation-induced cleavage of PARP-1 and down-regulated the expression of Rad51 and p-MAPK(ERK1/2). Conclusion Niraparib can increase the radiosensitivity of esophageal cancer cells by inhibiting cell proliferation, promoting cell apoptosis, inhibiting the repair of DNA damage and regulating the MARK-ERK signaling pathway.
		2023 Vol. 32 (8): 719-725 [Abstract] ( 84 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Review Articles

	726	Immunotherapy in the neoadjuvant chemoradiotherapy for locally advanced rectal cancer
		Li Haoyue, Jin Jing
		Long-course concurrent chemoradiotherapy (CCRT) or short-course radiotherapy (SCRT) prior to surgery and postoperative chemotherapy is one of the main standard therapies for patients with locally advanced rectal cancer (LARC). On this basis, total neoadjuvant therapy (TNT) has been shown to improve disease-free survival, distant metastasis-free survival and complete response rates, whereas the 3-year distant recurrence rate is still above 20% and pathological complete response (pCR) is less than 30%. Long-term survival and adverse reactions remain to be improved. Currently, significant achivement has been obtained in immunotherapy. Application of immunotherapy in the treatment of rectal cancer remains to be urgently validated. In recent years, immunotherapy combined with preoperative chemoradiotherapy has been adopted for LARC in clinical trials. Besides, immunotherapy alone, especially programmed death-1 (PD-1) / programmed death ligand-1 (PD-L1) inhibitor, has also been utilized to treat colon rectal cancer. Relevant research progress was reviewed in this article.
		2023 Vol. 32 (8): 726-731 [Abstract] ( 90 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	732	Research progress on the bone-marrow sparing intensity-modulated radiotherapy for cervical cancer
		Wang Jia'nan, Yu Xi, Su Qiuyue, Liu Dongmei, Xia Jingqi, Yang Shanshan
		The cisplatin-based concurrent chemoradiotherapy (CCRT) has been accepted as a standard treatment for most locally advanced cervical cancer. Compared with radiation therapy alone, CCRT can increase tumor control and survival rates, whereas it also can increase the incidence of acute hematological toxicity, which results in the treatment interruption or delay, and may even affect clinical efficacy and prognosis of patients. Therefore, how to reduce the incidence and severity of acute hematological toxicity induced by CCRT is a hot spot of clinical research. Previous studies have demonstrated that the occurrence of hematological toxicity is associated with the volume and dose of irradiated pelvic bone marrow. With the development of modern radiotherapy technology, precise radiotherapy technologies, such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), not only guaranteed the enough dose for tumor, but also realized the protection of normal tissues. This article will focus on the feasibility of bone marrow sparing during CCRT for cervical cancer, and summarize the research progress in recent years.
		2023 Vol. 32 (8): 732-736 [Abstract] ( 86 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	737	Research progress on the effect of hyperthermia on vascular endothelial growth factor in tumor microenvironment
		Cong Yuan, Shao Yun, Zhou Xuexiao, Shen Pei, Wang Shengzhi
		Vascular endothelial growth factor (VEGF) plays an important role in promoting tumor vascular growth and changing vascular wall permeability. With the in-depth study of tumor hyperthermia and tumor microenvironment, more and more studies have shown that hyperthermia exerts multiple regulatory effects on VEGF in tumor microenvironment. Combined with current research progress in China and abroad, this article reviews the effect of hyperthermia on VEGF and its related cells and factors in tumor microenvironment, aiming to provide new ideas for the clinical application of tumor hyperthermia combined with immune or targeted therapy.
		2023 Vol. 32 (8): 737-742 [Abstract] ( 89 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	743	Research progress on radiobiological effects of ferroptosis in cancer
		Wang Tianxiang, Du Mingyu, Zhang Pingchuan, Yin Li, He Xia
		Ferroptosis is a new form of regulated cell death discovered in recent years, which is iron-dependent cell death characterized by peroxidation of polyunsaturated fatty acid phospholipids. Recent studies have shown that radiotherapy can induce ferroptosis in cancer cells via ionizing radiation. Targeting ferroptosis plays a synergistic role in tumor suppression with radiation, which not only further deepens the connotation of radiobiology, but also provides a new perspective for tumor radiosensitization. This review systematically summarizes the occurrence and defense of ferroptosis, focusing on the key role of ferroptosis in the radiobiological effects of tumor cells and the potential application of ferroptosis in radiosensitization.
		2023 Vol. 32 (8): 743-747 [Abstract] ( 102 ) [HTML 1KB] [ PDF 0KB] ( 0 )

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