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Objective:To evaluate the usability of Gafchromic HD-V2 film for dose dosimetry in the ultra-high dose-rate (UD) electron beam from a modified medical linac, and to investigate the response between the energy and dose-rate dependence to the film.Methods:The HD-V2 film was utilized to measure the average dose-rate of the UD electron beam. The measured result was compared with those by advanced Markus chamber and alanine pellets. And characteristics of the UD electron beam were also measured by HD-V2 film. Energy dependence of HD-V2 film at three beam energies (6 MV X-ray, 9 MeV and 16 MeV electron beam) was investigated by obtaining and comparing the calibration curves based on the clinical linear accelerator in the dose range of 10-300 Gy. The dose-rate dependence of HD-V2 film was also studied by varying the dose rate among 0.03 Gy/s, 0.06 Gy/s and 0.1 Gy/s, and range of 100-200 Gy/s.Results:The measured average maximum dose-rate of 9 MeV UD electron beam at source skin distance (SSD) 100 cm was approximately 121 Gy/s using HD-V2 film, consistent with the results by advanced Markus chamber and alanine pellets. The measured percentage depth dose (PDD) curve parameters of the UD electron beam were similar to the conventional 9 MeV beam. The off-axis dose distribution of the UD electron beam showed the highest central axis, and the dose was gradually decreased with the increase of off-axis distance. The energy dependence of HD-V2 film had no dependency of 6 MV and 9, 16 MeV while measuring the dose in the range from 20 to 300 Gy. The HD-V2 film had no significant dose-rate dependency at the dose rate of 0.03 Gy/s, 0.06 Gy/s and 0.1 Gy/s for the clinical linear accelerator. Likewise, there was also no dose-rate dependence in the range 100-200 Gy/s in the modified machine.Conclusion:HD-V2 film is suitable for measuring ultra-high dose rate electron beam, independent of energy and dose rate.
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Objective:To compare the effects on DNA strand break induced by ultra-high dose rate (FLASH) electron beam and conventional irradiation, and investigate whether FLASH effect was correlated with a reduction of radiation response.Methods:Aqueous pBR322 plasmid was treated with FLASH (125 Gy/s) and conventional irradiation (0.05 Gy/s) under physioxia (4% O 2) and normoxia (21% O 2). Open circle DNA and linear DNA were detected by agarose gel electrophoresis, and the plasmid DNA damage was quantified with an established mathematical model to calculate the relative biological effect (RBE) of DNA damage. In some experiments, Samwirin A (SW) was applied to scavenge free radicals generated by ionizing radiation. Results:Under physioxia, the yields of DNA strand breakage induced by both FLASH and conventional irradiation had a dose-dependent manner. FLASH irradiation could significantly decrease radiation-induced linear DNA compared with conventional irradiation ( t=5.28, 5.79, 7.01, 7.66, P<0.05). However, when the aqueous plasmid was pretreated with SW, there was no difference of DNA strand breakage between FLASH and conventional irradiation ( P>0.05). Both of the yields of open circle DNA and linear DNA had no difference caused by FLASH and conventional radiotherapy at normoxia, but were significantly higher than those under physioxia. In addition, the yields of linear DNA and open circle DNA induced by FLASH irradiation per Gy were (2.78±0.03) and (1.85±0.17) times higher than those of conventional irradiation, respectively. Conclusions:FLASH irradiation attenuated radiation-induced DNA damage since a low production yield of free radical in comparison with conventional irradiation, and hence the FLASH effect was correlated with oxygen content.
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Objective:To investigate the feasibility of transforming conventional medical accelerator to achieve ultra-high dose rate required to achieve Flash radiotherapy (Flash-RT), and to understand the physical properties of the Flash-RT beam.Methods:By transforming the Varian 23CX medical accelerator, the radiation average dose rate at the isocenter was not less than 40 Gy/s. The relevant physical measurement scheme was designed to accurately measure the actual radiation dose rate of different source skin distance (SSD) conditions, the percent depth dose (PDD) curve and the off-axis dose distribution of the beam.Results:The average dose rate of 9 MeV electron beam after the transformation was measured using the HD-V2 type film, the average dose rate of 3 s was 97.9 Gy/s, and the average dose rate of 6 s was 99.27 Gy/s. When the SSD was 100 cm, 80 cm and 60 cm, the average dose rate of 9 MeV electron beam after the transformation was 99.3 Gy/s, 168 Gy/s and 297.5 Gy/s, respectively. After the transformation, the R100 of the 9 MeV beam was 2.2 cm underwater, R50 was 3.87 cm underwater, the electron range Rp was 4.58 cm, and the maximum possible energy Ep,0 on the phantom surface was 9.28 MeV. These parameters were slightly higher than those of the conventional 9 MeV beam, manifested with slight increase in the surface dose and widening high dose flat area. The overall deposit dose distribution exhibited the highest central axis and the increase in dose declines from the axis distance. Under the condition that the field size was 20 cm×20 cm and the SSD was 100 cm, the FWHM of the vertical and horizontal off-axis dose distribution curves were 16.6 cm and 16.4 cm, respectively. Conclusion:By transforming conventional medical accelerator, the average dose rate of the beam at the isocycle meets the requirement of Flash-RT, and the average dose rate under the condition of 60 cm SSD is much higher than the requirement of at least 40 Gy/s for Flash-RT.
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Objective:To analyze the data of ultra-high dose rate (FLASH) radiotherapy in GEO (Gene Expression Omnibus) database by bioinformatics method, in order to find the hub genes involved in flash radiotherapy induced acute T-lymphoblastic leukemia.Methods:The gene expression profiles of malignant tumors receiving FLASH radiotherapy were downloaded from GEO database. The R software was used to screen the differential expressed genes (DEGs) and analyze their biological functions and signal pathways. The protein-protein interaction (PPI) network of DEGs was analyzed by online tool of STRING, and Hub genes were screened by Cytoscape plug-in. The expressions of screened Hub genes in acute T lymphoblastic leukemia were identified with TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) database.Results:Based on the analysis of GSE100718 microarray dataset of GEO database, a total of 12 800 genes were found to be associated with radiosensitivity of acute T lymphoblastic leukemia, of which 61 significantly altered DEGs were selected for further analysis. It was found that these genes were involved in the biological processes of metabolism, stress response, and immune response through the pathways of oxidative phosphorylation, unfolded protein response, fatty acid metabolism, and so on. PPI analysis indicated that HSPA5 and SCD belonged to the Hub genes involved in the regulation of FLASH radiosensitivity, and they were significantly highly expressed in acute T lymphoblastic leukemia combined with TRD/LMO2-fusion gene.Conclusions:Through bioinformatics analysis, the Hub genes involved in regulating the sensitivity of FLASH radiotherapy and conventional radiotherapy can be effectively screened, and thus the gene expression profiles can be used to guide the stratification of cancer patients to achieve a precise radiotherapy.
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Objective:To propose an automatic planning approach for Eclipse15.6 planning system based on Eclipse scripting application programming interface (ESAPI) and evaluate its clinical application.Methods:20 patients with nasopharyngeal carcinoma and 20 cases of rectal cancer were selected in the clinical planning. The developed automatic planning script SmartPlan and RapidPlan were used for automatic planning and dosimetric parameters were compared with manual planning. The differences were compared between two groups by using Wilcoxon signed rank test. Results:The dosimetric results of automatic and manual plans could meet clinical requirements. There was no significant difference in target coverage in nasopharyngeal carcinoma planning between two groups ( P>0.05), and automatic plans were superior to manual plans in organs at risk sparing ( P<0.05). Except for the homogeneity index of PTV and the maximum dose of bowel in rectal cancer plans, the other dosimetric parameters of the automatic plans were better than those of the manual plans (all P<0.05). Conclusions:Compared with the manual plans, the automatic plans have the same or similar target coverage, similar or better protection of organs at risk, and more convenient implementation. The developed SmartPlan based on ESAPI has clinical feasibility and effectiveness.
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Objective:To propose an automatic planning method of intensity-modulated radiotherapy (IMRT) for esophageal cancer based on dose volume histogram prediction and beam angle optimization in Raystation treatment planning system.Methods:50 IMRT plans of esophageal cancer were selected as the training set to establish a dose prediction model for organs at risk. Another 20 testing plans were optimized in Raystation using RuiPlan and manual method, and the beam angle optimization and dose volume histogram prediction functions of RuiPlan were used for automatic planning. Dosimetric differences and planning efficiency between two methods were statistically compared with paired t-test. Results:There were no significant dosimetric differences in the conformity index (CI), homogeneity index (HI) of PTV, V 5Gy of both lungs and D max of the spinal cord between automatic and manual plans (all P>0.05). Compared with those in the manual plans, the V 20Gy and D mean of the left and right lungs generated from automatic plans were reduced by 1.1%, 0.37 Gy and 1.2%, 0.38 Gy (all P<0.05), and the V 30Gy, V 40Gy and D mean of the heart in automatic plans were significantly decreased by 5.1%, 3.0% and 1.41 Gy, respectively (all P<0.05). The labor time, computer working time, and monitor unit (MU) number of automatic plans were significantly decreased by 65.8%, 14.1%, and 17.2%, respectively (all P<0.05). Conclusion:RuiPlan automatic planning scripts can improve the efficiency of esophageal cancer planning by dose prediction and beam angle optimization, providing an alternative for esophageal cancer radiotherapy planning.
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Objective:To validate the accuracy of physical model of in-vivo 3D dose verification based on electronic portal imaging device (EPID) using the phantom and preliminarily analyze the clinical application.Methods:Two phantoms (uniform and non-uniform phantoms) were involved in this study. The system of in-vivo 3D dose verification based on EPID was employed to acquire the images of square fields (SF) and combined fields of intensity-modulated radiotherapy (CFIMRT). The physical model of different media was constructed using the system. The factor of γ passing rate under different dose/distance criteria was statistically compared. For clinical cases, the dose-volume histograms were adopted to analyze the dose distribution of target volume and organs at risk (OARs).Results:For the SF in the uniform phantom, the average γ passing rate (3%/3 mm) was (97.49±1.11)%, and (94.06±5.11)% for the SF in the non-uniform phantom ( P>0.05). No statistical significance was noted in IMRT using different delivery methods (all P>0.05). For clinical cases, the average γ passing rate (3%/2 mm) was (97.96±1.84)% in the pre-treatment dose verification, and (90.51±6.96)%(3%/3 mm) for the in-vivo 3D dose verification. For clinical cases, significant dose deviation was observed in OARs with small size and large volume changes. Conclusion:The in-vivo 3D dose verification model based on EPID can be effectively applied in inter-fraction dose verification, providing technical support for adaptive radiotherapy in clinical practice.
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Objective:Based on the AAPM-TG218 report, the dose verification of intensity-modulated radiotherapy (IMRT) plans were classified to understand the current status, establish the process and determine the limits of dose verification in our hospital.Methods:Different combinations of tumor locations, accelerators, treatment planning systems and verification devices in our hospital were verified and compared to determine the tolerance limits and action limits of each combination. The measurement requirement was adopted according to the AAPM-TG218 report, and 80 cases were selected for each measurement. The measurement procedures were implemented based upon the AAPM-TG218 report and clinical experience of our hospital.Results:The clinical action limits of IMRT plans in our hospital could meet the recommended range of the AAPM-TG218 report, and the tolerance limits were slightly lower than the AAPM-TG218 report′s recommendation (93.94% for 3%/2 mm). The measurement of verification devices was related to the sensitivity. The tolerance limits measured by EPID were higher than ArcCHECK, especially when the dose/distance requirements were more stringent (94.12% and 92.03% for 3%/2 mm, P=0.074; 86.82% and 74.61% for 2%/2 mm, P=0.017). Conclusion:Through the AAPM-TG218 report, the work flow of IMRT dose verification and the limit range are established in our hospital, providing guidance for subsequent clinical dosimetric measurement.
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As a method for local treatment, radiotherapy plays a key role in the management of tumors. In the past few decades, great progress has been made in radiotherapy technology, with improvements in conformity, homogeneity, and radiotherapy efficiency, and the results are encouraging. Nevertheless, the maximum tolerated dose of normal tissue has limited the further increase in radiotherapy dose in the tumor area. If radiation-induced toxicities can be reduced, a higher radiotherapy dose can be delivered to tumor tissue, so as to achieve a better treatment response. In recent years, the unique FLASH effect of ultra-high-dose-rate radiotherapy (FLASH-RT) is capable of maintaining a consistent tumor response whilst reducing radiation-induced toxicities in normal tissue, and therefore, FLASH-RT has become a research hotspot in the field of radiotherapy across the world. At present, some scholars tend to explain the FLASH effect using the theory of acute oxygen depletion, but the protective effect of FLASH-RT on normal tissue remains to be clarified. In addition, preliminary clinical studies have been conducted for FLASH-RT, and the results are promising. Based on existing evidence, this article elaborates on the research advances in FLASH-RT in the treatment of malignant tumor, so as to provide a reference for the translation and application of this new technique.
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Objective To compare the clinical target volume (CTV) expanding margins in the mid-and upper-thoracic esophageal carcinoma during radiotherapy measured with and without online image guidance technique by CT on rail.Methods 100 patients with mid-and upper-thoracic esophageal carcinoma undergoing intensity modulated radiotherapy received CT scanning.Image registration was conducted between the scanning results and the planned CT images,thus set-up error data were acquired and got on-line correction.Fifty patients were randomly selected to undergo additional post-treatment CT scanningso as to analyze the revised residuals,displacement during treatment,and infra-fraction GTV shifts.Results Compared to the radiotherapy without CT-based image guidance,the CTV expanding margins obtained with CT-based image guidance was reduced significantly from 9.1,8.8 and 6.1 mm to 4.1,4.5 and 4.3 mm in the left-right,head-feet,and belly-back directions respectively.Conclusions The on-line image-guided technology significantly improves the accuracy of target and reduces the CTV expanding margins.