Chinese Journal of Radiation Oncology

中华放射肿瘤学杂志

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Chinese Journal of Radiation Oncology

	2022 Vol.31 Issue.5 Published 2022-05-15

	Abdominal Tumors Thoracic Tumors Review Articles Investigation Research Consensus Guidelines Physics·Technique·Biology

Investigation Research

	405	Infrastructure of radiation oncology in China:a national survey for development and allocation of radiotherapy equipment during the 14^th Five-Year Plan period
		Expert Group for the 14-Five-Year Plan of Radiotherapy Equipments Development and Allocation, Qiu Jie, Yang Bo, Chai Shuang, Wang Lyuhua, Zhang Fuquan
		Objective To investigate the current status of radiotherapy personnel and equipment in China, and to provide data basis for scientific allocation and effective use of radiotherapy equipment during the 14^th Five-year Plan period. Methods From October to December 2020, a group of experts from China Association of Medical Equipment carried out an online questionnaire investigating the basic situation of radiotherapy in China, and the contents of the survey include radiotherapy centers, professional personnel, equipment, technology, equipment utilization rate, forecast of personnel and equipment in the next five years, etc. The data were reviewed by provincial medical societies/associations. Results There were 1538 radiotherapy centers and 32978 radiotherapy professionals in Mainland China, including 18966 radiotherapy physicians, 4475 physicists and 9537 technicians. There were 2139 linear accelerators, 57 cobalt 60 accelerators, 457 afterloaders, 6 proton/heavy ion machines, 1034 conventional 2D simulators, 1208 CT simulators, and 89 MR simulators. 1459 centers can provide 3D conformal radiotherapy, 1256 centers can deliver intensity-modulated radiotherapy, 514 centers can offer volumetric modulated arc therapy, 422 centers can provide brachytherapy. According to the estimated data reported by the participating centers, in the next five years, the demand of professionals and machines will be increased by 4868 radiotherapy physicians, 2078 physicists and 3796 technicians, and 994 linacs, 896 CT simulators, 313 MR simulators and 54 proton heavy ions. Conclusions The radiotherapy industry in China grows fast. During the 14^th Five-Year Plan period, the radiotherapy industry still has strong market demand as well as increase demand of personnel and equipment. Strengthening the market competitiveness of domestic radiotherapy enterprises, improving the equipment utilization rate in primary hospitals, providing comprehensive and systematic training and promoting standardized clinical application can resolve the issues of the lack and unbalanced distribution of radiotherapy resources, and maintain the fast and sustainable development of radiotherapy in China.
		2022 Vol. 31 (5): 405-409 [Abstract] ( 184 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Guidelines

	410	Absorbed dose determination in high-energy photon beams and electron beams based on standards of absorbed dose to water
		National Cancer Center/National Cancer Quality Control Center
		The calibration of absorbed dose of medical electronic linear accelerator is one of the most important contents of radiotherapy quality control. In particular, the widespread application of precision radiotherapy puts forward higher requirements for the accuracy of radiotherapy dosimetry. Compared with the absorbed dose dosimetry procedure based on calibration factor in terms of air kerma/exposure, the advantages of the absorbed dose dosimetry based on calibration factor in terms of absorbed dose to water are:reduced uncertainty, no quantity conversion factors, simpler physical concept and simpler calculation formula, etc. According to relevant existing standards, this guideline specifies the dosimetry procedures and relevant requirements for high-energy beams of medical linac based on calibration factor of absorbed dose to water, provides guidance for domestic medical institutions to determine the absorbed dose of high-energy photon and electron beams, and provides support for the development of precision radiotherapy.
		2022 Vol. 31 (5): 410-420 [Abstract] ( 91 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Consensus

	421	Consensus on taxonomy of planning automation for radiotherapy
		Men Kuo, Hu Weigang, Zhang Yibao, Wang Pei, Yin Yong, Dai Jianrong
		Powered by big data and artificial intelligence, the research and clinical application of treatment planning automation for radiation therapy are rapidly growing. The application and supervision of planning automation systems necessitate careful consideration of different levels of automation, as well as the context for use. For autonomous vehicles, the levels of automation have been defined at home and abroad. Nevertheless, no such definitions exist for radiotherapy planning automation. To promote and standardize the development of radiotherapy planning automation and initiate discussion within the community, we developed this recommendation with reference to the taxonomy of driving automation for vehicles and divided the radiotherapy planning automation into six levels (level 1 to 6).
		2022 Vol. 31 (5): 421-424 [Abstract] ( 118 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Thoracic Tumors

	425	*Simultaneous integrated boost vs.* routine IMRT in limited-stage small-cell lung cancer:an open-label,non-inferiority,randomized, phase 3 trial**
		Zhan Tianyou, Zhang Tao, Zhou Zongmei, Yan Wenbin, Zhai Yirui, Deng Lei, Wang Wenqing, Bi Nan, Wang Jianyang, Wang Xin, Liu Wenyang, Xiao Zefen, Feng Qinfu, Chen Dongfu, Lyu Jima, Hui Zhouguang, Liang Jun, Wang Lyuhua
		Objective Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy. Methods Patients diagnosed with treatment-naiveand confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1:1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2Gy/2.15Gy/28F,PTV 50.4Gy/1.8Gy/28F) or conventional fractionated radiotherapy (PTV 60Gy/2Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity. Results Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95%CI:35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%(HR=1.22,95%CI:0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%(HR=1.35,95%CI:0.90-2.04,P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%(HR=0.98,95%CI:0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups (HR=1.69,95%CI:1.18-2.41,P=0.003;HR=1.72,95%CI:1.09-2.70,P=0.018;HR=1.66,95%CI:1.01-2.73,P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64,95%CI:1.15-11.57,P=0.028). The most common grade 3–4 adverse events were myelosuppression (21.7% vs. 15.4%,P=0.83),radiation pneumonitis (4.7% vs. 2.7%,P=0.44) and radiation esophagitis (3.8% vs. 1.8%,P=0.51). Conclusions Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.
		2022 Vol. 31 (5): 425-430 [Abstract] ( 104 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	431	Precision thoracic radiotherapy in limited-stage small cell lung cancer:a network meta-analysis
		Yang Tao, Cao Lijuan, Jiang Xiaodong, Fan Yuwei, Li Jia, Wu Dan, Chen Hanbo, Xia Youyou
		Objective To systematically evaluate the efficacy and safety of precision thoracic radiotherapy (TRT) in the limited-stage small cell lung cancer (LS-SCLC) patients by network meta-analysis. Methods Randomized controlled trials (RCTs) of TRT regimes in the LS-SCLC were electronically searched from PubMed, Web of Science, The Cochrane Library, CNKI and Wanfang Data from inception to September 1^st, 2021. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Statistical analysis was performed by Stata 17 and R 4.1.1software. Results A total of 6 RCTs involving 1730 patients with six radiation regimens including hyperfractionated radiotherapy (HFRT):HFRT₄₅(45Gy/30 F) and HFRT₆₀(60Gy/40 F);conventional fractionated radiotherapy (CFRT):CFRT₇₀(70Gy/35 F) and CFRT₆₆(66Gy/33 F);moderately hypofractionated radiotherapy (MHFRT):MHFRT₆₅(65Gy/26 F) and MHFRT₄₂(42Gy/15 F) were included. The network meta-analysis showed that:in terms of improving progression-free survival and overall survival, there was no statistically significant difference among the six radiotherapy regimens. The probabilistic ranking results were:MHFRT₆₅ > HFRT₆₀ > CFRT₆₆ > CFRT₇₀ > MHFRT₄₂ > HFRT₄₅, and HFRT₆₀ > MHFRT₆₅ > CFRT₆₆ > CFRT₇₀ > HFRT₄₅ > MHFRT₄₂, respectively. The HFRT₆₀ regimen was superior to other regimens in reducing the incidence of grade ≥3 pneumonia, and there was no difference between the regimens in causing grade ≥3 radiation esophagitis, and the results of ranking probability were:HFRT₆₀ > MHFRT₄₂ > CFRT₆₆ > CFRT₇₀ > HFRT₄₅ > MHFRT₆₅, and HFRT₆₀ > CFRT₇₀ > CFRT₆₆ > HFRT₄₅ > MHFRT₄₂ > MHFRT₆₅, respectively. Conclusions HFRT₆₀ radiotherapy regimen may be more effective and safer in the treatment of LS-SCLC patients as a priority choice for LS-SCLC TRT. Limited by the number and quality of included studies, the above conclusions need to be verified by more high-quality studies.
		2022 Vol. 31 (5): 431-437 [Abstract] ( 103 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Abdominal Tumors

	438	Analysis of patterns of recurrence and prognostic factors in 171 locally advanced gastric cancer patients with radiotherapy and concurrent chemotherapy after radical gastrectomy
		Ma Yifu, Yang Yongqiang, Xing Pengfei, Wu Yongyou, Zhang Liyuan
		Objective To retrospectively analyze prognostic factors and patterns of recurrence in locally advanced gastric cancer patients receiving chemoradiotherapy (CRT) after radical gastrectomy, aiming to provide reference for postoperative CRT of locally advanced gastric cancer. Methods Clinical data of 171 patients with curatively resected gastric carcinoma who received postoperative CRT in our hospital between 2008 and 2020 were retrospectively analyzed. The disease-free survival and overall survival (OS) rates were calculated by Kaplan-Meier method. Univariate prognostic analysis was performed by log-rank test. Multivariate prognostic analysis was conducted by Cox model. Results The median follow-up duration was 63 months. The follow-up rate was 93.6%. 31.0% and 66.7% of the enrolled patients were classified in pathological stage Ⅱ and Ⅲ. The acute grade 3 or 4 gastrointestinal and hematological toxicity rates were 8.8% and 9.9%, respectively. In total, 166 patients completed the entire CRT regimen. No toxicity-related death occurred. Regarding patterns of recurrence, 17 patients had locoregional recurrence, 29had distant metastasis and 12had peritoneal metastasis. The 1-, 3-and 5-year overall survival (OS) rates were 83.7%, 66.3%, and 60.0%, while the 1-, 3-and 5-year disease-free survival rates were 75.5%, 62.7%, and 56.5%, respectively. In the multivariate analysis, pathological T stage, perineural invasion and lymph node ratio (LNR) were found to be the independent predictors of OS. Conclusions Postoperative intensity-modulated radiation therapy and chemotherapy are well tolerated, with acceptable toxicities and encouraging locoregional tumor control and long-term survival. LNR can be used as an independent prognostic indicator for OS. Adjuvant CRT should be considered for all patients with a high risk of locoregional recurrence.
		2022 Vol. 31 (5): 438-444 [Abstract] ( 93 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	445	Study of 3D-printed multi-channel applicator in patients treated with brachytherapy after cervical cancer surgery
		Tang Chengqiong, Liu Jiangping,Gulina Kuerban, Liu Hao, Cao Yaofeng, Zhang Xiaofang, Zhong Wei
		Objective To compare the dosimetric difference between 3D-printed multi-channel applicator and conventional vaginal single-channel applicator for brachytherapy, aiming to provide guidance for patients receiving brachytherapy after cervical cancer surgery. Methods From January 2019 to November 2020, 25 cervical cancer patients complicated with VAIN Ⅲ receiving ¹⁹²Ir high-dose-rate brachytherapy after cervical cancer surgery were selected. Each patient was located by CT scanning with 3D-printed multi-channel applicator and conventional vaginal single-channel applicator, and corresponding plan and evaluation were carried out. The dose volume histogram (DVH) was obtained by inverse dose optimization algorithm. The dosimetric differences of high-risk clinical target volume (HRCTV), bladder and rectum during brachytherapy were compared with those of source applicators. The optimal treatment plan was selected. Results D90%, D100%, V100% and V150% of the plans designed by 3D-printed individual multi-channel applicator had no significant differences compared with those designed by conventional single-channel applicator (all P>0.05). The bladder and rectal D2cm³designed by 3D-printed multi-channel applicator were significantly lower than those using conventional single-channel applicator, and the differences were statistically significant (both P<0.05). Conclusion The multi-channel individual applicator target made by 3D-printing technology has good conformal property, properly protects the bladder and rectum and possesses treatment advantages over conventional single-channel applicator.
		2022 Vol. 31 (5): 445-449 [Abstract] ( 124 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Physics·Technique·Biology

	450	The application and correlation study of γ rule and DVH evaluation for VMAT dose verification evaluation of cervical cancer patients
		Ma YangGuang, Mai Rizhen, Pei Yuntong, Wang Fangna, Liu Lele, Guo Yuexin
		Objective To evaluate the volumetric modulated arc therapy (VMAT) dose verification of cervical cancer based on γ rule and dose volume histogram (DVH) and to perform correlation analysis between the evaluation results and the dose differences. Methods Twenty cervical cancer VMAT plans were selected and performed on TrueBeam Linac. The delivered point and surface dose was measured by FC-65G and ArcCheck and the results were compared to those calculated by Eclipse. The dose of patients was reconstructed by 3DVH. Then, differences between the reconstructed and plan value of Dmean,D95%,D98% and D2% of PTV, V20Gy of left and right femoral head, V40Gy of rectum, D1cm³ of cord, D98%,D2% and D50% of the 50% prescription iso-dose volume (IDV), were evaluated and 3-dimensional (3D) γ was assessed for each organ. Lastly, Pearson’s correlation coefficient was used to analyze the relationship between point dose difference, 2D γ pass-rate (γ%), γmean and 3D γ% of each organ and the dose difference. Results Small differences were found between the point dose measured, reconstructed and the plan value. Differences between Dmean of PTV, all dose parameters of IDV and plan values were all within 3% and V40Gy of rectum showed the largest difference. As for the 3D γ%, the maximum pass rate was found for the left and right femoral head and the maximum variance for cord D1cm³. There was a moderate correlation between measured and reconstructed point dose deviation and dose difference of each organ, while no significant correlation was found for 2D γ%. Strong correlation was found between 3D γ% of target and D50% of PTV/IDV and no correlation was found for other organs. Conclusion The performance of both γ-and DVH-based evaluation can reveal dose error for dose verification, but both of them have some limitations and should be combined in clinical practice.
		2022 Vol. 31 (5): 450-455 [Abstract] ( 91 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	456	*Effect of upregulated HuR* gene on radiosensitivity of esophageal squamous cell carcinoma cell Kyse450**
		Han Dan, Li Lu, Kan Zhiwen, Tao Zhenchao, Qian Liting
		Objective To evaluate the effect of upregulation of HuR gene on the radiosensitivity of esophageal squamous cell carcinoma cell Kyse450. Methods The HuR gene of Kyse450 cells was upregulated by lentivirus. At the same time, X-ray irradiation at a dose of 6Gy was selected as the intervention condition. Western blot and qPCR were used to detect the expression levels of protein and RNA after Kyse450 transfection, respectively. CCK8 kit was employed to determine the cell proliferation rate. Clone formation assay was adopted to evaluate the ability of cell clone formation. Wound healing experiment and the Transwell test were performed to detect changes in cell migration. Results CCK8 assay showed that the proliferation ability of cells was enhanced after upregulation of HuR gene, and this enhancement trend was more obvious after radiation. The plate cloning experiment showed that with the increase of radiation dose, the clone formation rates were decreased in both groups, but the clone formation rate in the overexpression group was higher than that in the control group. Wound healing experiment and Transwell test demonstrated that the wound healing rate and migration ability in the overexpression group were higher than those in the control group, and the difference was more significant after radiotherapy. Western blot showed that the levels of MMP9 and MMP2 at 24h after radiotherapy in the overexpression group were higher than those in the control group. Conclusion The upregulation of HuR can enhance the proliferation, cloning, migration capabilities and decrease the radiosensitivity of esophageal squamous cell carcinoma cells.
		2022 Vol. 31 (5): 456-461 [Abstract] ( 100 ) [HTML 1KB] [ PDF 0KB] ( 0 )

Review Articles

	462	The mechanism and clinical research progress on radiotherapy combined with immunotherapy in esophageal cancer
		Gao Linrui, Xiao Zefen
		Radiation therapy (RT) is one of main methods of comprehensive treatment of esophageal cancer (EC). It plays a dual role in the immune system and can activate systemic immune response. However, the effect of tumor cytotoxicity induced by RT is limited, and it can induce abscopal effect in combination with immunotherapy (IT). A number of clinical studies have shown the effect and great potential of immune checkpoint inhibitors (ICIs), such as PD-1/L1 antibodies in advanced EC. Besides, RT and ICIs exert a synergistic effect. Currently, multiple ongoing studies related to concurrent radiochemotherapy combined with IT is expected to determine the efficacy of this comprehensive treatment in EC and elucidate the efficiency and cost-effectiveness.
		2022 Vol. 31 (5): 462-467 [Abstract] ( 98 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	468	Clinical features of patients with EGFR mutation-positive non-small cell lung cancer and brain metastases
		Zhu Yixiang, Zhang Ye
		Advanced non-small cell lung cancer (NSCLC) patients are commonly with brainmetastases, leading to poor survival and quality of life. Epidermal growth factor receptor (EGFR) is common sensitive mutation type in NSCLC. Compared with other molecular types, it has different molecular biological characteristics. For patients with brain metastases and EGFR-mutated advanced NSCLC, EGFR-tyrosine kinase inhibitors can prolong overall survival and improve intracranial and extracranial control rate. To understand the characteristics of brain metastases of patients with sensitively EGFR-mutated NSCLC, the incidence, onset time, site, number and size of lesions, symptoms, targeted treatment effect and disease outcomes were reviewed, which can provide reference for interventional timing and local treatment technology selection of local treatment for brain parenchymal metastases.
		2022 Vol. 31 (5): 468-472 [Abstract] ( 94 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	473	Progress on radiotherapy of primary central nervous system lymphoma
		Li Panpan, Zhang Zhuo
		Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma that occurs in the brain, spinal cord, meninges or eyes. Diffuse large B-cell lymphoma accounts for the vast majority, of which non-GCB subtype is more common. The median survival time of untreated patients is only 3 months. Surgical removal of the tumor alone has no obvious survival benefit. Early single use of whole brain radiation therapy (WBRT) yields a high remission rate, but the duration is short, and delayed neurotoxicity is an important complication, especially for elderly patients. Subsequent studies found that high-dose methotrexate-based chemotherapy combined with WBRT significantly improved the prognosis of this disease. However, combination therapy increases the risk of neurotoxicity, and this strategy has been questioned. In recent years, reduced-dose WBRT and autologous hematopoietic stem cell transplantation have gradually replaced the previous standard-dose WBRT. This article reviews the progress on the radiotherapy for PCNSL.
		2022 Vol. 31 (5): 473-477 [Abstract] ( 79 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	478	Research progress on high-dose-rate brachytherapy of localized prostate cancer
		Guo Wei, Sun Yunchuan
		Brachytherapy has played an important role in localized prostate cancer. High-dose-rate brachytherapy has evolved over the decades, as either monotherapy or in combination with external beam, it offers many advantages over other treatment alternatives. Precise control over dose delivery allows for focal dose escalation while sculpting dose around organs at risk to maintain excellent tolerance. The high dose per fraction exploits the low α/β ratio of prostate cancer and triggers transcriptional changes in the tumor genome, thereby enhancing radiation sensitivity. In this article, the development, patient selection, application of techniques, clinical efficacy and adverse events for high-dose-rate brachytherapy were summarized.
		2022 Vol. 31 (5): 478-482 [Abstract] ( 99 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	483	Progress on basic research and clinical application of hyperthermia combined with immune checkpoint inhibitors
		Liu Pengyuan, Wu Yajun, Wu Zhibing
		Malignant tumor is a persistent disease that perplexes public health. Traditional treatment appears ineffective for patients with advanced metastasis. In recent years, immune checkpoint inhibitor therapy has developed rapidly and has great potential, but the overall clinical efficiency is still low. Carcinoma changes the tumor microenvironment through various mechanisms, resulting in immune resistance, which greatly reduces the efficacy of immune checkpoint inhibitors. Hyperthermia can not only play the anti-tumor advantage of thermal effect, but also play a direct and indirect immune sensitization effect through a variety of ways, transforming"cold tumor" into"hot tumor", to enhance the impact of immune checkpoint inhibitors in many patterns. Numerous basic experiments have proved that hyperthermia combined with immune checkpoint inhibitors has achieved a classy impression in mice. Presently, some ongoing clinical trials of hyperthermia combined with immune checkpoint inhibitors have gained promising progress. In this paper, the merits of combination therapy were analyzed from three aspects:immune checkpoint inhibitors, hyperthermia, hyperthermia combined with immune checkpoint inhibitors, and the future research directions of hyperthermia combined with immune checkpoint inhibitors were prospected.
		2022 Vol. 31 (5): 483-487 [Abstract] ( 126 ) [HTML 1KB] [ PDF 0KB] ( 0 )

	488	Research progress on bolus materials used for radiotherapy
		Lu Ying, Shi Qinying, Wang Yong, Huang Xiaobo
		It is necessary to place bolus on skin to increase the surface dose when using high-energy rays to treat superficial lesions because of its build-up effect. It is well known that the set-up reproducibility of hand-made bolus is poor, and the main concern of commercialized bolus is the inadvertent air gap between the bolus and irregular skin. Owing to the advantage of making individualized and complex-shaped bolus, 3D-printing technology is playing an important role in making the bolus. The aim of this review is to summarize the current research status of hand-made, commercialized and 3D-printed bolus materials and future development trend of the bolus, providing reference for clinical application.
		2022 Vol. 31 (5): 488-492 [Abstract] ( 91 ) [HTML 1KB] [ PDF 0KB] ( 0 )

中华放射肿瘤学杂志

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