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.

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.

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.

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.

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.

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.

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.

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.

Objective:To compare the radiation chemistry effects on water molecules after ultra-high dose rate (FLASH) and conventional irradiation.Methods:Both FLASH and conventional irradiation were applied to ultrapure water, with the hydroxyl radical yield in the homogeneous phase detected using electron paramagnetic resonance (EPR) and the hydrogen peroxide (H 2O 2) yield in the diffusion phase analyzed uuxing fluorescence probe. The liposome model was then established to investigate the radiation chemistry effect of FLASH and conventional irradiation in inducing lipid peroxidation. Results:Radiation chemistry reactions were observed in water molecules after irradiation. In the homogeneous phase, the yield of free radicals using FLASH irradiation is similar to those from conventional irradiation ( P>0.05). In the diffusion phase, the amount of H 2O 2 produced by FLASH irradiation was significantly lower than those from conventional irradiation ( t=0.49-12.81, P<0.05). The liposome model confirmed that conventional irradiation could significantly induce lipid peroxidation through the radiation chemistry effect in water molecules as compared with FLASH irradiation ( t=0.31-11.73, P<0.05). Conclusions:The radiation chemistry effect in water molecules after FLASH irradiation was significantly lower than that from conventional irradiation. This could be one of the mechanisms of FLASH effect.

Objective:To conduct a comparative analysis of the radiation damage to zebrafish embryos and the associated biological mechanism after ultra-high dose rate (FLASH) and conventional dose rate irradiation.Methods:Zebrafish embryos at 4 h post-fertilization were exposed to conventional and FLASH irradiation (9 MeV electron beam). The mortality and hatchability of zebrafish after radiation exposure were recorded. Larvae at 96 h post-irradiation underwent morphological scoring, testing of reactive oxygen species (ROS) levels, and analysis of changes in oxidative stress indicators.Results:Electron beam irradiation at doses of 2-12 Gy exerted subtle effects on the mortality and hatchability of zebrafish embryos. However, single high-dose irradiation (≥ 6 Gy) could lead to developmental malformation of larvae, with conventional irradiation showing the most significant effects ( t = 0.87-9.75, P < 0.05). In contrast, after FLASH irradiation (≥ 6 Gy), the ROS levels in zebrafish and its oxidative stress indicators including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were significantly reduced ( t = 0.42-15.19, P < 0.05). There was no statistically significant difference in ROS levels in incubating solutions after conventional and FLASH irradiation ( P > 0.05). Conclusions:Compared to conventional irradiation, FLASH irradiation can reduce radiation damage to zebrafish embryos, and this is in a dose-dependent manner. The two irradiation modes lead to different oxidative stress levels in zebrafish, which might be a significant factor in the reduction of radiation damage with FLASH irradiation.