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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 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 build a systemic and automatic importing scheme for importing CT images and structures into the treatment planning systems (TPSs) of Eclipse and Monaco.Methods:Based on two TPSs of Eclipse and Monaco, the files of CT images and structures were automatically transported from OAR auto-delineation system to the importing directory of these two TPSs using batch script in Windows system. Following the standard importing procedures of these two TPSs, the automatically importing script of CT images and structures were developed using the application of UiBot. Finally, the CT images and structures were imported into these two TPSs opportunely.Results:By comparing the importing time using script and manual methods, the script not only achieved auto-importing CT images and structures into TPSs, but also yielded almost the same efficiency to manual method. The number of imaging layers in most patients was between 130 and 180, and the average manual and automatic importing time within this interval was 76 s and 75 s.Conclusions:Automatic scripts can be developed by using the automation function of UiBot combined with the actual problems of radiotherapy and repeated workflow. The efficiency of radiotherapy work can be significantly improved. Manual and time costs can be saved. It provides a novel alternative for the automation of radiotherapy procedures.
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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:In this paper, based on the 4D dose distribution of the treatment plan, the effects of respiratory movement on the dose distribution of three-dimensional conformal radiation therapy (3DCRT) and sliding window intensity-modulated radiation therapy (SW-IMRT) techniques were analyzed, and the dose errors caused by respiratory movement based on the 4D dose distribution were evaluated.Methods:In this study, the dynamic thoracic phantom (CIRS-008A) was used to simulate the patient with a 3 cm spherical insert as the tumor. Four motion patterns were simulated with cos 4( x) and sin ( x) wave forms of 10 mm and 5 mm amplitudes. The 4DCT scans with the phantom were performed in different breathing modes, and the maximum intensity projection (MIP), average intensity projection (AIP) and 10 separate 4DCT phase images were transferred to the Eclipse treatment planning system. The targets were contoured on MIP, with corresponding 3DCRT and SW-IMRT plans designed and dose calculated on AIP. By copying the plan designed on the AIP to each phase image of the 4DCT set, the MATLAB software package was employed to register and superimpose all the phase-specific doses onto one of the reference phase to create a 4D-accumulated dose distribution. Both films (EBT2) and optically stimulated luminescence (OSLD) detectors were inserted in and around the target area of the phantom to measure the delivered doses. The calculated 4D-accumulated doses were compared to the measured doses and their differences were evaluated using Gamma analysis. Results:Under different respiration modes, the average Gamma index (3%/3 mm) passing rates between the 4D-accumulated doses and EBT2-measured doses for 3DCRT and SW-IMRT plans were (98.8±0.78)% and (96.4±1.89)%, respectively. The absolute measurements of OSLDs both inside and outside of the target area well matched the 4D-accumulated doses.Conclusions:4DCT can be effectively applied to evaluate the treatment plan dose distribution through 4D dose accumulation, which can potentially avoid cold spots and target under-coverage. Under different respiration modes, both 3DCRT and SW-IMRT plans provide dose measurements consistent with those predicted by the 4D-accumulated dose of treatment plan.
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Objective:To propose an automatic planning platform of the Raystation planning system suitable for multi-disease and multi-plan technique by using the Raystation built-in script function.Methods:IronPython and WPF user interface framework were utilized for programming and resolving the differences in the design of different types of plans for different diseases. The program was designed from prescription identification, visual plan parameter input and cost-function setting. The efficiency of automatic planning and manual planning was compared when applied in whole brain irradiation, nasopharyngeal carcinoma, cervical cancer, esophageal cancer and breast cancer, including IMRT and VMAT. The dosimetric parameters of the whole brain irradiation were chosen.Results:Physicists were only required to enter and select the necessary parameters to achieve the plan design by using the program. Compared with the five types of diseases, the maximum efficiency of automatic planning was 1.4 times higher than that of manual planning. In the dosimetric evaluation of the whole brain irradiation plan, both manual and automatic planning could meet the clinical needs, and the D 2%, CI and HI of the target area did not significantly differ (all P>0.05). The mean D 98% of the target area and the D max of lens in the manual plan were significantly higher than those in the automatic plan by 0.4% and 7.1%(both P<0.05). Conclusion:The developed program has the function of automatic planning system, which can realize the automatic planning of multi-disease and multi-type radiotherapy, significantly improve the efficiency of plan design and has important clinical application value.
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Objective To study the effect of PinXl on radiosensitivity and ROS level of esophageal cancer cells.Methods Esophageal cancer cells were divided into control group (no cell transfection),radiation group (8 Gy of X-rays),PinX1 group (pDsRed1-PinX1 transfect to overexpression,radiation+PinX1 group (8 Gy X-rays after pDsRed1-PinX1 transfection).Cell proliferation was measured by MTT assay,cell apoptosis was measured by flow cytometry,the activation levels of Caspase-3 and Caspase-9 in cells were measured by Western blot,the cellular ROS level was determined using DCFH-DA probe,and the cell radiosensitivity was evaluated by the colony formation assay.The subcutaneous xenograft tumor model of EC9706 cells was established with nude mice,and each group received local irradiation every 4 days 8 Gy five fractions γ-rays.The nude mice bearing PinX1-transfected cells were implanted with PinX1 plasmid into tumor before radiotherapy to investigate the relationship between PinX1 overexpression and radiosensitivity in xenotransplantation mice models.Results Compared with control group cells,the survival rate of EC9706 cells of radiation group or PinX1 group decreased significantly from 100％ to (67.92±4.71) ％ and (83.14 ±4.01) ％ (t =9.433,4.957,P＜0.05),the apoptosis rate increased significantly from (6.47± 1.46) ％ to (44.38±4.16) ％ and (25.42 ±2.78) ％ (t =12.882,6.439,P ＜ 0.05),Caspase-3 activation level increased (t =6.655,2.531,P ＜0.05),and the activation level of Caspase-9 and cellular ROS was also significantly increased.Compared with radiation group cells,the cell viability of radiation+PinX1 group decreased from (67.92 ±4.71) ％ to (52.73 ±5.58) ％ (t =8.942,P＜0.05),the apoptosis rate increased from (44.38±4.16) ％ to (55.29±4.98)％ (t=3.707,P＜0.05),the activation levels of Caspase-3,-9,and the level of ROS in cells was increased (t =15.435,17.990,4.526,P＜0.05).The radiosensitivity of EC9706 cells was increased after PinX1 transfection with a sensitization ratio of 1.408.The volume of xenograft tumor with PinX1 overexpression cells in nude mice was significantly smaller than control.Conclusions Overexpression of PinX1 could inhibit the proliferation,induce apoptosis and increase the radiosensitivity of esophageal cancer cells.
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Objective To investigate the effect of respiratory motion on inadvertent irradiation dose (ⅡD)to the microscopic disease(MD)and expanding margin of target volume in stereotactic body radiotherapy for lung cancer. Methods Based on the pattern of respiration-induced tumor motion during lung radiotherapy, a probability model of MD entry into or exit from internal target volume(ITV)was established and the theoretical dose to MD was calculated according to the static dose distribution by four-dimensional computed tomography. The experimental dose to MD during respiratory motion was measured using a respiration simulation phantom and optically stimulated luminescence(OSL)and then compared with the theoretical value for model validation.Results For the target volume in periodic motion,the deviation of the theoretical dose to MD from the experimental value measured by OSL was less than 5%. A 10-mm margin around ITV received a biological dose higher than 80 Gy. Conclusions The dose model established in this study can accurately predict the irradiation dose to MD in the target volume in periodic motion. Respiratory motion increases ⅡD to MD and there is no need to expand clinical target volume.
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Objective To investigate the efficacy and toxicity of stereotactic ablative radiotherapy for stage Ⅰ peripheral non-small cell lung cancers.Methods Thirty six patients of stage Ⅰ peripheral non-small cell lung cancers were treated with stereotactic ablative radiotherapy.The prescription dose was 12 Gy per fraction ×4 fraction in one to two weeks.The 100％ planning target volume (PTV) was covered by the isodose curve of 95％ prescription dose.Organs at risk and their respective tolerance doses used during treatment planning were developed from the research scheme of the Radiation Therapy Oncology Group 0236.Before the radiation delivery,all patients were scanned by the fan beam CT or the cone beam CT for image guidance and registration.The follow-up for the patients was given to observe the toxicity and efficacy of stereotactic ablative radiotherapy (SABR).Results The median follow-up time was 18.7 months (range of 4 to 36 months).After treatment,the overall response rate was 88.9％,with complete response (CR) 17 cases(47.2％),partial response (PR) 15 cases(41.7％),and stable disease (SD) 4 cases(11.1％).The estimated overall survival rate at 1 and 3 years was 92.3％ (95％ confidence interval [CI],86.3％ ～97.1％) and 85.3％ (95％ CI,80.5％ ～90.6％).The estimated local control rate at 3 years was 90.2％ (95％ CI,85.7％ ～94.8％).There was no gradeⅢ or above toxicity related to treatment.Conclusions The stereotactic ablative radiotherapy attains good local control and survival efficacy for the stage Ⅰ peripheral non-small lung cancer patients.It is well tolerated owing to low toxicity.
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Objective To investigate the accuracy of CTVision image-guided stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC).Methods 10 lung SBRT patients were imaged with CTVision before and after irradiation for acquiring and analyzing the three-dimensional set-up error data sets in our department from October 2010 to May 2012.Gross tumor volumes (GTVs) were contoured on pre-and post-SBRT CT sets and combined for generating internal gross tumor volumes (IGTVs).Planning target volume (PTV) margin was calculated,and IGTVs and PTVs were compared for off-line verification of accuracy of SBRT.A paired t-test statistical analysis was conducted with the datasets using SPSS 17.0.Results 80 CT image sets were totally obtained.Setup errors was significant difference before and after radiotherapy in the left-right,superior-inferior and anterior-posterior directions,that were (-0.10±1.30) mmand (-0.15±1.31) mm (P=0.720),(0.18±1.32) mm and (0.18±1.43) mm (P =1.000) and (-0.08 ± 1.19) mm and (-0.13 ± 1.18) mm (P =0.750),respectively.IGTVs of ten patients were smaller than corresponding PTVs (13.53 cm3 and 37.84 cm3,P =0.000).Conclusion Accuracy and safety of SBRT could be verified by imaging with CTVision before and after delivery for non-small cell lung cancer.
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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.
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ObjectiveTo quantitatively characterize the inter-fractional anatomy variations and advantages of dosimetry for the adaptive radiotherapy in pancreatic cancer.MethodsA total of 226 daily CT images acquired from 10 patients with pancreatic cancer treated with image-guided radiotherapy were analyzed retrospectively.Targets and organs at risk (OARs) were delineated by the atlas-based automatic segmentation and modified by the skilled physician.Various parameters,including the center of mass (COM) distance,the maximal overlap ratio (MOR) and the Dice coefficient (DC),were used to quantify the inter-fractional organ displacement and deformation.The adaptive radiation therapy (ART) was applied to handle the daily GT images.The dose distributions parameters from the ART plan were compared with those from the repositioning plan.ResultsThe inter-fractional anatomy variations of pancreas head were obvious in the pancreatic cancer irradiation.The mean COM distance,MOR and DC of pancreas head after the bony or soft tissue alignment and registration was ( 7.8 ± 1.3 ) mm,( 87.2 ± 8.4 )％ and ( 77.2 ±7.9)％ respectively.Compared with the repositioning plan,the ART plan had better target coverage and OARs sparing.For example,the mean V100 of PTV was improved from (93.32 ± 2.89) ％ for repositioning plan to ( 96.03 ± 1.42) ％ for ART plan with t =2.79,P =0.008 and the mean V50.4 for duodenum was reduced from (43.4 ± 12.71 )％ for the repositioning plan to (15.6 ± 6.25)％ for the ART plan with t =3.52,P=0.000.ConclusionsThe ART can effectively account for the obvious inter-fractional anatomy variations in pancreatic cancer irradiation and be used to escalate the radiotherapy dose for the pancreatic cancer,which will lead to a promising higher local control rate.