Image-guided Stereotactic Radiotherapy For Lung Cancer: Technique Aspects & Clinical Application

ⅠEstablishment of Image-guided Radiation Therapy(IGRT) Technique1.Quality Assurance Program for a Kilovoitage Cone-beam CT Guided Radiation Therapy SystemPurpose To establish the quality assurance(QA) program for a kilovoltage cone-beam computer tomography(kVCBCT) guided radiation therapy system.Materials and Methods The QA program of this study included three parts:safety and functionality,geometrical accuracy of the system and imaging performance of the kVCBCT.During the 4 months,we evaluated the functionality of safety features and the clinical operation of the entire system during the tube warm-up process.We assessed the displacement between the center of the kV X-ray volume image and the MV treatment center using the Ball-Bearing phantom.Qualitative evaluation of imaging performance was performed using the Catphan^?500 phantom.The test items of the imaging performance included low contrast resolutions,spatial resolutions and the Hounsfield Unit(HU) uniformity.Results All safety and functionality tests passed on a daily basis.Geometrical accuracy of the system was tested four times.The displacement between the center of the kV X-ray volume image and the MV treatment center was all less than 0.5mm. The maximal difference is 0.43 mm,0.43 mm and 0.28 mm in the lateral,longitudinal and vertical direction,respectively.The low contrast resolutions of the imaging ranged between 1.3%and 1.8%,and the HU uniformity ranged between 0.7%and 1.6%.The spatial resolutions of the four tests were all 71p/cm.Conclusions We have developed a comprehensive,yet practical,set of QA tests for the kVCBCT guided radiation therapy system.Use of the tests over extended periods show that the kVCBCT guided radiation therapy system can work safety and functionality with reliable mechanical accuracy and stable image quality. 2.Image Alignment Methods Evaluation of the Image-guided Lung Cancer Radiotherapy2.1 Reproducibility evaluation of the manual image alignment method for kilovoltage cone-beam CT guided lung cancer radiationPurpose To evaluate reproducibility of the manual image alignment method for kilovoltage cone-beam CT(kVCBCT) guided lung cancer radiotherapy.Materials and Methods Sixteen non-small cell lung cancer patients entered into this study.Weekly on-line kVCBCT guided set-up error correction was performed.A total of ninety-six pretreatment kVCBCT images were available for analysis.The landmarks of the manual alignment included the cranial part of the lung and spine. Images were aligned in three dimensions,and the LR(left-right),SI (superior-inferior),and AP(anterior-posterior) components of translation of the target isocenter were documented and analyzed for each registration.Intra-observer variability was investigated:at least one week after treatment all kVCBCT studies were reexamined by the same physician.Additionally,all kVCBCT studies were examined by a second physician,a radiation therapist and inter-observer variability was tested.Results The intra-observer variability of the manual registration method was investigated.All kVCBCT scans were re-evaluated by the same physician.Compared with the original results,the percentage of the more than 3 mm differences in LR,SI, and AP directions are 0,13%and 6%,respectively.The percentage of the more than 3 mm differences in LR,SI,and AP directions between two physicians are 11%,19% and 14%.The difference of the registration results between radiation therapist and physician in LR,SI,and AP directions are 16%,27%and 27%.Conclusions The reproducibility of the manual alignment method was poor, especially in the inter-observer evaluation.The optimal alignment method for kVCBCT guided lung cancer radiation needs further research.2.2 Impact of the Clipbox size on the image registration results for image-guided radiotherapy:a phantom studyPurpose To investigate the impact of the Clipbox size(region of interesting for automatic image registration) on the results of gray value based automatic image alignment method for kilovoltage cone-beam CT(kVCBCT)guided radiotherapy.Materials and methods The CIRS Thorax phantom Model was used in this study. Three fiducial markers were attached on the phantom.And the phantom was aligned with the laser using attached fiducial markers.This setup assumes that a laser-based phantom alignment represents an accurate alignment.After setup,kVCBCT of the phantom was acquired.The procedure was repeated ten times and ten kVCBCT scans of the phantom were acquired.A reference model for the image alignment comparison was made before the evaluation.The acquired ten kVCBCT scans of the phantom were retrospectively matched with planning CT using gray value based automatic image registration method with four different Clipbox.Four groups of registration result with different Clipbox were compared with the reference model,respectively.Results There is only one Clipbox,which include the whole region of the thoracic, can get the exact image registration result when compared with the reference model, but it take more time than any other three Clipboxes to complete the image alignment.Conclusions Based on the phantom study,the Clipbox,which include the whole region of the thoracic,was selected as the optimal regions for automatic image registration.2.3 Study of different registration methods for on-line kilovoltage cone-beam CT guided lung cancer radiation:selection and evaluationPurpose To select the optimal registration method for on-line kilovoltage cone-beam CT(kVCBCT) guided lung cancer radiation and evaluate the reproducibility of the selected method.Materials and Methods Sixteen non-small cell lung cancer patients were entered into this study.A total of ninety-six pretreatment KVCBCT images from sixteen patients were available for analysis.Bone-based automatic registration,gray-based automatic registration,annual registration and semi-automatic registration method were used for image registration.All registrations were accomplished by one physician.Another physician evaluated the results of each registration and selected the optimal registration method in blind.Intra-observer and inter-observer variability of this selected image registration protocol were investigated. Results The score of the bone-based automatic registration,gray-based automatic registration,annual registration and semi-automatic registration method was 2.4,2.7, 3.0 and 3.7,respectively.The score of the four different groups has statistics significant difference(F=42.197,P＜0.001).The intra-observer variability of the selected registration method was investigated.Compared with the original results,the differences in LR(left-right),SI(superior-inferior),and AP(anterior-posterior) directions have no statistics significant difference.The inter-observer variability of the SI directions has statistics significant difference(t=-2.790,P=0.008).The difference of the registration results between radiation therapist and physician in SI(t=-2.490, P=0.018) and AP(t=-2.425,P=0.021) directions both have statistics significant difference.Conclusions Because of the highest score and accepted reproducibility, semi-automatic registration method was selected for kVCBCT guided lung cancer radiation. ⅡEstablishment of Image-guided Stereotactic Body Radiation Therapy(IG-SBRT) Technique for Lung Cancer3.The Comparison of CBCT and Slow CT in Determining the ITV for Lung Cancer PatientPurpose To compare the role of kilovoltage cone-beam CT(kVCBCT) and slow CT in determining the internal target volume(ITV) for lung cancer patient.Materials and Methods Fourteen patients with pathologically confirmed peripheral non-small cell lung cancer were entered into this study.There were two females and twelve males.The median age of these patients was 72 years(range:47-81).T-stages of these tumors were T1 in four patients,T2 in ten patients.There were seven tumors located in upper lobe,three in middle lobe and four in lower lobe.One fast CT(slice thickness 3 mm,revolution time 1s/slice),one slow CT(slice thickness 3 mm, revolution time 4s/slice)which limited to the tumor region and three kVCBCT scans were performed during quiet respiration for each patient.The scanning time of one kVCBCT was 2 minutes and the reconstructed slice thickness is 3 mm.Slow CT and kVCBCT were all aligned to the fast CT.After contouring the gross target volume (GTV)/ITV,5 mm margin was performed to generate clinical target volume(CTV). The volume of ITV-c(generated from the first kVCBCT) and ITV-s(generated from slow CT) were compared.Overlap volume of CTV(generated from fast CT) and ITV-c were compared with overlap volume of CTV and ITV-s.Results The volume of ITV-s and ITV-c had no statistics difference(p=0.099).The overlap volume of CTV and ITV-c was 64.1 cc and the overlap volume of CTV and ITV-s was 59.6 cc.These two overlap volume meet no significant statistics difference (p=0.061).Conclusions KVCBCT has the same role as slow CT in capturing the tumor movement and determine the ITV for lung cancer patient. 4.The Determination of Planning Target Volume(PTV) Margin for Cone-beam CT Guided Stereotactic Lung Cancer RadiationPurpose To assess the planning target volume(PTV) margin,which based on the residual set-up error and intrafraction patient motion,of the kilovoltage cone-beam CT(kVCBCT) guided stereotactic radiotherapy for lung cancer patients.Materials and Methods From Mar 2007 to Dec 2008,20 lung patients,who received stereotactic radiotherapy in our hospital,were included in this study.After patients were positioned using their skin marks,kVCBCT scans were performed before treatment and aligned to planning CT scans using the self-developed semi-automatic alignment method.Treatment table were repositioned according to the alignment results.A second kVCBCT scan was acquired immediately after the table correction. Residual set-up errors were calculated by aligning the second kVCBCT with the planning CT,using the semi-automatic alignment method.The third kVCBCT was got after each fraction of treatment.The intrafraction patient motion was evaluated according the alignment of the third kVCBCT and planning CT.Results 89 kVCBCT scans were used for residual error evaluation.The average residual set-up error(±SD) was -0.2±1.3mm,0.1±1.3mm and 0.3±1.3mm in the left-right(LR),superior-inferior(SI) and anterior-posterior(AP) direction, respectively.45 kVCBCT scans were used for intrafraction patient motion assessment. The intrafraction patient motion(±SD) was 0.5±1.3 mm,-0.5±2.1 mm and 0.1±2.1 mm in the LR,SI and AP direction,respectively.According to the results of residual set-up error evaluation and intrafraction patient motion assessment,3.2,4.5 and 3.7 mm should be applied to the margin of PTV in the LR,SI and AP direction, respectively.Conclusions On the basis of the residual set-up error and intrafraction patient motion measurements,the margin required for the cone-beam CT guided stereotactic lung cancer radiation would be approximatively 5 mm. 5.The Optimal Beam Margin Selection for Imaging-guided Stereotactic Lung Cancer RadiationPurpose To select the optimal beam margin for kilovoltage cone-beam CT(kVCBCT) guided stereotactic lung cancer radiotherapy.Materials and Methods Three lung cancer patients with different volume of gross target volume(GTV)(2.02cc,22.23cc and 50.36cc) were entered into this study.In order to evaluate the impact of beam margin on the dose distribution of stereotactic radiotherapy plan,five plans with different beam margin(0 mm,1 mm,2 mm,3 mm and 4 mm) were generated for each patient.All the plans were normalized to ensure that 95%of the planning target volume(PTV) at least receives the prescription dose and compared quantitatively.Based on these plans,the relationships between the beam margin and quantities such as the percentage of PTVC received dose, homogeneity index(HI),gradient score index(GSI) and the normal lung dose were assessed for different patients.In this study,clinical target volume(CTV) was established 0 mm.PTVC was the region of potential CTV to receive the incidental dose.Results The dose of 95%PTVC and HI were enlarged when beam margin become bigger and bigger.The 95%PTVC received dose of the three different patients was 31.0Gy,29.5Gy and 31.5Gy with 2 mm beam margin.The biggest GSI of the three patients were 32.2,51.4 and 80.8,when beam margin was established as 1 mm,2mm and 1mm,respectively.The minimal mean lung dose of the first patient was 333.3cGy with 1mm beam margin.The minimal mean lung dose of the other two patients was 464.0cGy and 493.3cGy,when beam margin established as 0 mm.Conclusions Based on the dose of 95%PTVC,the relationship between GSI and normal lung dose,2 mm may be the optimal beam margin for the imaging-guided stereotactic radiation lung cancer patients. ⅢClinical Application of the Image-guided Stereotactic Body Radiation Therapy(IG-SBRT) Technique for Lung Cancer6.Clinical Outcomes of the Image-guided Stereotactic Body Radiation Therapy (IG-SBRT) for StageⅠNon-Small Cell Lung CancerPurpose To evaluate the safety and efficacy of kilovoltage cone-beam CT(kVCBCT) guided stereotactic body radiation therapy for stageⅠnon-small cell lung cancer (NSCLC).Materials and Methods Eligible patients included clinical staged T1 or T2(≤7 cm), N0,M0,biopsy-confirmed NSCLC.SBRT treatment dose was 50Gy total in four fractions for peripherally located tumor or 48Gy in six fractions for centrally located tumor within 1-2 weeks.Daily kVCBCT guidance was performed for all patients to ensure the precise and accuracy of the treatment.Results From May 2007 to Feb 2009,14 patients with 15 tumors(3 with stage T1 and 12 with stage T2) were entered into this study.The median volume of GTV was 32.48cc(4.48-116.16cc).Of 14 patients,1 died of brain metastases and 1 died of pneumonia for the re-radiation of the recurrent mediastinal lymph node at a median follow-up period of 14 months.The 1-year crude local control rates and the 1-year overall survival rates were 100%and 90.6%,respectively.Three patients developed Grade 2 pneumonitis.Two patients developed Grade 2 chest wall pain.No therapy-related toxicity of Grade≥3 was observed.Conclusions IG-SBRT seems feasible and effective for stageⅠNSCLC.With the help of image guidance,even bigger tumor can be treated safely by this precise and accuracy method.