Gastric Cancer Radiotherapy Affect The Target Uncertainty Factors And Their Impact On The Dose Distribution Analysis

PartⅠ:Quantify the Set-upUncertainties Associatedwith Gastro-Intestinal Cancer TreatmentPurpose:It is often a trade-off between the adequate target coverage and normal tissue sparing when expanding CTV to PTV by a proper margin.The margin should be sufficient to account for all geometric uncertainties to ensure that CTV receives the prescribed dose during the treatment.Set-up uncertainties can be categorized into two components:systematic error and random error.It is essential to quantify the set-up uncertainties in post-operative gastric cancer radiotherapy as it will provide the clinical baseline for the PTV margin expension.Material and methods:From Jan.2005 to Nov.2006,22 patients with post-operatively confirmed gastric cancer were enrolled in this study.All patients were T3/N+,stagingⅡ-Ⅳ.Surgical clips were implanted in the surgical bed as fiducial marks.Patients were immobilized with a vac-lock, and were CT scanned and treated with Active Breathing Control(ABC).For each patient,a pair of anterior and lateral images were taken and compared to the computer-generated setup DRR to derive the R-L,A-P and S-I set up errors. The maximum,minimum,mean shift and standard deviation along R-L,A-P and S-I directions were calculated.The absolute shift from the intended targeting isocenter location,3D shift vector,was also calculated based on the shift along three axis.The frequency of the shift occurrences was then calculated and plotted.The proper margin was estimated based on the obtained dataResults:For all patients,systematic setup error is the mean of the standard deviations of each individual patient' s setup error.The random setup error for the entire group is the standard deviation of the mean setup errors of each individual in that group.The largest shift observed was along the superior-inferior direction, while the lateral direction has the smallest shift.To ensure that CTV is covered at least 95%of the times,the margin in x-,y-and z-axis should be 3.2mm,8.3mm and 6.4mm,respectively.The asymmetrical appearance of the frequency distribution curves of S-I shift implies that there is a systematic setup error along S-I direction.3D shift vector is calculated and shows at least 10 mm is needed to achieve 92%probability of CTV coverage.Conclusion:In the post-operative radiation of gastric cancer,the set up error along x-,y-and z-axis are independent from each other.The shift along the superior-inferior direction is the most significant.A non-uniform margin should be used in CTV expansion.A possible reduction in setup margin can be achieved with Image-guided radiotherapy(IGRT)with on-line or off-line correction while maintain the target coverage. PartⅡ:Organ Motion Related UncertaintiesPurpose:The 3D conformal radiotherapy and intensity modulated radiotherapy (IMRT)have provided us tools to shape radiation dose to highly conform to the target.Any organ motion of during the treatment has a detrimental effect on the delivered dose,especially when the dose is very conformal to the clinical target volume.Respiratory motion affects tumor in the abdomen region.Managing the respiratory motion with ABC(Active Breathing Control) in the post-operative radiation of gastric cancer is the subject of this project.Material and methods:Patient selection,immobilization,image acquisition and treatment method is the same as in PartⅠ.All patients were trained with steady breath hold as long as 40 seconds.Training can be up to 5 days.Image J software was used in image processing,motion measurement and data analysis. Images were processed with AHE and clips are marked in each APand lateral view fluoroscopy movies.Clips identified in fluro images were used for tracking and measurement in free breathing and ABC motion range study.All image frames were superimposed along time-axis to generate z-projection images in Image-J to show the motion range of each clip.And the motion range of each clip was measured in the resultant z-projection image.Results:For each patient,the max,min,mean and standard deviation of the motion range of each clip identified in the fluoro movies(with free breathing or with ABC)are calculated For free breathing,S-I motion is the largest: 10.0 mm and R-L motion is the smallest:5.8 mm.The average motion range for all clips for all images are 11.0 mm(S-I),5.5 mm(A-P)and 2.0mm(R-L). With ABC to minimize the motion caused by free breathing,the motion range reduced significantly in the S-I and A-P directions(p＜0.01).The average motion range along three axes is 2.2mm(S-I),1.1mm(R-L)and 1.7mm(A-P). However,residual motion existing under ABC,and intra-fraction and inter-fraction clip position variation were observed.For all the patients, the intra-fraction motion during one breath hold(ABC breath hold residual motion)in the S-I direction is the largest(2.2 mm)and R-L direction is the smallest(1.1 mm).The maximum intra-fraction clips shift for different breath hold in the same treatment fraction include the residual motion.The average maximum motion range along the three axes is S-I:3.7 mm,R-L:1.6mm and A-P 2.8mm.The inter-fx clips motions are measured by first registering the vertebral bodies on two images taken on different days to eliminate the set up errors.The average intra-fraction motion as clips mean position center-to-center along the three axis is S-I:2.7 mm,R-L:1.7mm and A-P 2.5 mm.Conclusion:In the treatment of post-operative gastric cancer,organ motion induced by respiration is measured by surgical clips displacement under free breathing and with ABC.For free breathing,S-I motion is the largest and R-L motion is the smallest.With the use of active breath control,motion can be reduced significantly in the S-I and A-P direction.The ABC residual motion is small during one breath hold.The variation between each breath hold within the same fraction and that between different fractions can change from day to day or from one breath hold to another.This posed the potential problems for ABC without IGRT.IGRT can improve the effectiveness of ABC technique greatly. PartⅢ:Uncertainties Associated with Target DelineationPurpose:Radiotherapy requires high accuracy in dose delivered to intended target.However,there are many error sources associated with the treatment preparation and execution that limit the overall treatment accuracy.The main sources of uncertainty are tumor delineation inaccuracies of the gross tumor volume(GTV),unknown extent of microscopic tumor(CTV),organ motion and patient setup variations.Variation in target delineation is the component of systematic uncertainties.Target delineation variation can arise from image acquisition,different imaging modalities,inter-and intra-observer variations.Although sometimes CT with contrast and other imaging modalities such as MRI,PET,etc are used in target delineation,conventionally only one planning CT is acquired for the treatment planning purpose.This CT data set can be considered as a "snapshot" of patient' s anatomical structure. Material and methods:Patient selection,treatment method,immobilization and image acquisition are the same as in the partⅠ.Three CT scans were acquired at different time on varies days.The time interval between CT simulation and food intake is more than 3 hours.These 3 CT data sets were first registered based on the vertebral bodies before one physician outlined the CTV,kidneys,liver and other structures on the three registered CT images. CTV1,CTV2 and CTV3 are compared in terms of volume,shape and position.The overlapping CTVs were generated using Boolean operator in ADAC.Results:The volumes of each CTV and the overlapping CTVs were calculated. Consistence of the CTV delineation is measured by calculating the percentage of overlapping of individual CTV.The average percentage of overlapping for the same physician is 80.3%.The inconsistence mostly lies at the edge of target.Conclusion:Target delineation variation is an important source of geometrical errors in radiotherapy and must be accounted for in margin design. Three CT images were acquired and used to study target delineation variation. The percentage of overlapping ranges from 89%to 68%.The results of this study show that taking multiple CT may improve the consistency of target delineation. PartⅣ:Uncertainties Induced by Organ DeformationPurpose:Organ deformation is an issue that is becoming increasingly import in the era of image-guided radiotherapy.We attempt to evaluate the extent of organ deformation in the post-operative gastric cancer treatment under free breathing and with active breath control.Material and methods:Patient selection,treatment method,immobilization, image acquisition is the same as in the partⅠ.A polygon was drawn to connect the identified clips in each captured image frame.18 or 19 polygons on 18 or 19 frames for each fluoro movie were superimposed to depict the organ deformation during free breathing and ABC.Results:The standard deviation(SD)of area variation is within 10%and SD of perimeter is within 5%for free breathing,while the SD of area variation with ABC is within 6%and the SD of perimeter is within 3%.That means the organ deformation during free breathing is usually minimal,however it is larger than that with ABC as ABC can effectively reduce the organ motion greatly,therefore minimizes the organ deformation.Conclusion:Our data suggests that polygon area change is a better measurement of organ deformation than polygon perimeter.Organ deformation can be quantified by the variation of the area and the perimeter.The organ deformation with ABC breath hold is minimal. PartⅤ:Dosimetric Effect of Uncertainties and Methods of Managing These UncertaintiesPurpose:Uncertainties analyzed and quantified in the previous parts including set up,organ motion,target delineation and organ deformation effect the dose delivered to patients.Traditionally,to account for those uncertainties,an adequate margin is added to the target to ensure that CTV actually receives prescribed dose.The conventional way of adding a margin to CTV to form PTV based on a 'rule of thumb' is not optimal to account for various uncertainties.Also,treatment planning is commonly performed on a static patient model,therefore,it dose not reflect the dosimetric effects of motion.With the help of the imaging tools available and with the implanted fiducial markers like clips we used in this study,the uncertainties related to the set-up and organ motion can be quantified.The dosimetric effect of PTV margin and various uncertainties in the treatment process can be therefore studied.Biological models such as TCP/NTCP can be used to predict the outcome and possible complications of the treatment. Image-guided radiation therapy is a effective tool to deliver conformal dose to the target and spare the surrounding normal tissue in the mean time.Material and methods:Treatment plans of eight patients with cardiac and antrum gastric cancer were selected from the whole group to evaluate the dosimetric effects of uncertainties.3D dose convolution,Gaussian PDF generation,dose image manipulation were performed with Image J.The static 3D conformal and IMRT treatment plans with different margins were generated in ADAC.The dose calculation grid resolution was set to 0.2 cm x 0.2 cm x 0.2 cm.Then the static 3D dose volume of each computer plan was exported from ADAC to Image-J,and convoluted with different PDFs to calculate the resultantdose images for free breathing organ motion effect(convolute with 3D free breathing motion PDF),random setup error(convolute with 3D Gaussian PDF),or ABC inter-fraction and/or intra-fraction errors(convolute with 3D Gaussian PDF).Finally the resultant dose images were imported back into ADAC for dose display and DVH calculation.NTCP/TCP and gEUD are also calculated using the biological model provided in ADAC planning system.Results:Currently patients with GI cancer are treated with prescribe dose of 45 Gy to CTV in 25 fractions.Dose distributions and DVHs Comparison for 3D Conformal and IMRT Treatment show that for static plans,theIMRT plans provides better dose coverage that 3D conformal plans with higher mean target dose and smaller dose standard deviation:99%(IMRT)vs 90%(3D conformal) for CTV coverage(p=0.01),90%(IMRT)vs 84%(3D conformal)for PTV coverage (p=0.04);IMRT plans have smaller average liver dose,V40 volume with 15% (IMRT)vs 18%(3D conformal)(p=0.01);and for average left kidney dose, IMRT plans have significantly smaller V15 volumes with 26%vs 41%(p=0.03), no difference on V15 of right kidney.For motion incorporated plans,IMRT plans also showed better CTV coverage with 98%vs 87%for 3DCRT;IMRT plans have lower V40 volumes of liver with 12%vs 3DCRT 16%(p=0.01)and lower V15 volume for left kidney,34%(IMRT)vs 50%(3DCRT)(p=0.03).In order to explore the possibility of dose escalation,we studied three treatment planning and delivery strategies on the same patient:A)treatment plan with free breathing margin,patient treated with normal free breathing; B)plan with 5 to 8 mm margin and treated with ABC with only weekly localization correction;C)plan with 5mm margin and treated with ABC and online correction IGRT.All plans demonstrated similar CTV coverage,better than 98%.Three strategies showed great difference in normal tissue sparing: liver V40 volume reduced with scheme B and C both in the static and motion incorporated plans(p=0.01).For dose to both kidneys,there was no different in the static plans.However,for motion plans,scheme B and C showed significant V15 and V18 volume reduction(p＜0.01).Based on TCP/NTCP model, additional 9Gy could be delivered to CTV,with IGRT online correction combined with ABC and maintain comparable toxicity to liver and kidneys.Conclusions:IMRT is a better treatment option than the conventional 3D conformal plan.We incorporated uncertainties associated with the treatment process such as organ motion,setup errors,inter- and intra-fraction motions into the static dose distributions to study their dosimetric effect. Comparison of three treatment planning and treatment delivery strategies showed that with a proper margin the uncertainties in treatment associated with each delivery option can be accounted for to deliver adequate CTV dose; and different margins and delivery options effect dose to critical structures. We also demonstrated the possibility of dose escalation with ABC combined with IGRT online correction strategy.