Objective To evaluate the dosimetric effects of target volume delineation with metal clip and seroma,alone or in combination,on external-beam partial breast irradiation (EB-PBI) based on four-dimensional computed tomography (4DCT).Methods Twenty female patients undergoing EB-PBI from 2009 to 2013 were enrolled as subjects.The gross tumor volumes (GTVs),GTVC,GTVS,and GTVC+S,were delineated on 4DCT images at 10 phases using metal clip,seroma,and both of them,respectively.The GTVS on 4DCT images at 10 phases were fused to generate the internal gross tumor volumes (IGTVS),IGTVC,IGTVS,and IGTVC+S.The planning target volumes (PTVS),PTVC,PTVS,and PTVC+S,were obtained via expansion of margin by 15 mm.The three-dimensional conformal radiotherapy plans were made by one physician based on PTVC,PTVS,and PTVC+S on end-inhalation images.The target volume,homogeneity index (HI),conformity index (CI),and doses to organs at risk were compared between the three groups.Results The C+S group had the largest IGTV,PTV,and the ratio of PTV to diseased breast volume,which was followed by the C group and the S group (all P＜ 0.05).The S group had significantly lower doses to the ipsilateral normal breast and lung than the C group and the C+S group (all P＜0.05).There were no significant differences in HI or CI between the three groups (all P＞ 0.05).Conclusions The volume variation caused by target volume dehneation on 4DCT images based on different references has little impact on dose distribution in target volume.However,it has substantial impact on radiation doses to the ipsilateral normal breast and lung.

Objective To investigate the correlations in target volumes based on positron emission tomography CT (PET/CT) and the end-expiration phase of four-dimensional CT (4D-CT) images for non-small cell lung cancer (NSCLC).Methods Seventeen patients with NSCLC sequentially underwent three-dimensional CT (3DCT),4D-CT and 18F-FDG PET/CT thoracic simulation scans.The gross target volume (GTV) was contoured on the end-expiration phase (50％) of 4D-CT and defined as GTV50％.The internal gross target volumes (IGTV) based on PET/CT images (IGTVPET) were determined by the standardized uptake value (SUV) 2.0 (IGTVPET2.0) and 20％ percentage of the maximal standardized uptake value (SUVmax) (IGTVPET20％).The following parameters were calculated to analyze the correlation between IGTVPET and GTV50％ in volume ratio (VR) and conformity index (CI):maximum transverse diameter of GTV50％,volume of GTV50％,the displacement of GTV in the cranial-caudal direction and 3D Vector calculated from 4D-CT dataset as well as the SUVmax.Results There was no significant correlation between the VR of IGTVPET2.0 to GTV50％ and the maximum transverse diameter of GTV50％,volume of GTV50％,the displacement of GTV in the cranial-caudal direction,3D Vector and the SUVmax (P ＞ 0.05).The VR between IGTVPET20％ and GTV50％ inversely related to maximum transverse diameter of GTV50％,volume of GTV50％ and SUVmax (r =-0.663,-0.669,-0.752,P ＜0.05).The CI between IGTVPET2.0 and GTV50％ positively related to volume of GTV50％ and maximum transverse diameter of GTV50％ (r =0.613,0.483,P ＜ 0.05).Conclusions 3D PET images provide a time-averaged image of the tumor during the numerous breathing cycle.They fail to include the full information of moving tumor.The target volumes based on 3D PET might not reflect the real IGTV of NSCLC.

Objective To investigate the differences in position and volume between planning target volumes (PTV) based on positron emission tomography?computed tomography (PET?CT) images with an standardized uptake value ( SUV) no less than 2?5, 20% of the maximum SUV ( SUVmax ), or 25% of SUVmax , three?dimensional ( 3D ) CT, and four?dimensional ( 4D ) CT in thoracic esophageal cancer. Methods Eighteen patients with thoracic esophageal cancer sequentially received chest 3DCT, 4DCT, and [18F]fluoro?2?deoxy?D?glucose (FDG) PET?CT scans. PTV3D was obtained by conventional expansion of 3DCT images;PTV4D was obtained by fusion of target volumes from 10 phases of 4DCT images. The internal gross tumor volumes ( IGTV) , IGTVPET2.5 , IGTVPET20%, and IGTVPET25%, were generated based on PET?CT images with an SUV no less than 2?5, 20% of SUVmax , and 25% of SUVmax , respectively. These IGTVs were expanded longitudinally by 3?5 cm and radically by 1 cm to make PTVPET2.5 , PTVPET20%, and PTVPET25%, respectively. Results PTV3D was significantly larger than both PTV4D and PTVPET(P=0?000 -0?044), while there was no significant difference between PTV4D and PTVPET ( P= 0?216 -0?633 ) . The mutual degrees of inclusion ( DIs ) between PTV3D and PTV4D were 0?70 and 0?95, respectively, which were negatively correlated with 3D?Vector ( P=0?039). The mutual DIs between PTVPET2.5, PTVPET20%, and PTVPET25% were 0?74, 0?72, 0?78, 0?73, 0?77, and 0?70, respectively, which showed no correlation with 3D?Vector (P=0?150 -0?822). The mutual DIs between PTV3D and PTVPET were 0?86, 0?84, 0?88, 0?63, 0?67, and 0?59, respectively. Conclusions It is difficult to achieve complete volumetric overlap of PTVs based on 3DCT, 4DCT and PET?CT in thoracic esophageal cancer due to different target volume information. PET scan during free breathing should be used with caution to generate PTVs in thoracic esophageal cancer.

Objective To analyze the volume and position of the gross tumor volumes (GTV) in primary esophageal cancer based on contrast-enhanced three-dimensional (3D),four-dimensional (4D) and cone beam (CB) computed tomography (CT).Methods A total of thirty-four patients underwent 3D-CT and 4D-CT simulation scans for computer treatment plan and contrast-enhanced CBCT scans were conducted prior to the first treatment.GTV3D,GTV4D50,internal GTVMIP (IGTVMIP) and internal GTVCBCT (IGTVCBCT) were delineated on 3D-CT,4D-CT50 (the end expiratory phase),4D-CTMIP (the maximum intensity projection),and CBCT datasets,respectively.The IGTV10 was defined as 10 respiratory phases GTVs in 4D-CT.To evaluate the difference in position,volume and the volumes encompassed characteristic.Results The significant difference was observed in the volumes [IGTV10 ＞ (IGTVCBCT or IGTVMIP) ＞ (GTV3D or GTV4D50)] regardless of the tumor location.Regarding IGTV10 as the standard volume,the underestimations or overestimations between IGTV10 and IGTVCBCT were larger than that of between IGTV10 and JGTVMIP (t =-8.294--3.192,P ＜ 0.05).However,there was no significant difference between the areas of IGTV10 which excluded in IGTVCBCT and IGTV3D (P ＞ 0.05).The GTV4D50/ IGTVCBCT ratio for upper esophageal tumors was negatively correlated to motion vector (r =-0.756,P ＜ 0.05).The centroid coordinates of IGTVCBCT in AP direction were significantly different from the test volumes (GTV3D,GTV4D50,IGTVMIP and IGTV10) (t =-3.559--2.435,P ＜ 0.05).The IGTV10/IGTVCBCT ratio was positively correlated to motion vector (r =0.695,P ＜ 0.05) for middle esophageal tumors.The centroid coordinates of IGTVCBCT were significantly different IGTV10 (t =2.201,P ＜0.05) in AP direction.For distal esophageal tumors,the significant difference was observed in the centroid coordinate between IGTVcBcT and IGTVMIP (t =-2.365,P ＜ 0.05) in LR direction.The percentage of IGTV10 excluded the IGTVcBcT were significantly correlated to the motion vector (r =0.540,0.678,P ＜ 0.05) for both middle and distal esophageal tumors.The mean MI value of IGTVCBCT to the other four test volumes ranged from 0.65 to 0.72.Conclusions CBCT has much motion information than 3D-CT but less than IGTV10.CBCT was similar to MIP images based on respiration motion.However,the target motion information encompassed in CBCT and MIP images cannot be exchanged to each other.

Objective To compare volumetric size, conformity index (CI), degree of inclusion (DI) of internal gross target volumes (IGTV) delineated on 4D-CT-MIP and PET-CT images for primary thoracic esophageal cancer. Methods Fifteen patients with thoracic esophageal cancer sequentially underwent enhanced 3D-CT, 4D-CT and PET-CT simulation scans. IGTVMIP was obtained by contouring on 4D-CT maximum intensity projection ( MIP). The PET contours were determined with nine different threshold methods (SUV≥2?0, 2?5, 3?0, 3?5), the percentages of the SUVmax(≥20%, 25%, 30%, 35%, 40%) and manual contours. The differences in size, conformity index (CI), degree of inclusion ( DI) of different volumes were compared. Results The volume ratios ( VRs) of IGTVPET2. 5 to IGTVMIP , IGTVPET20% to IGTVMIP, IGTVPETMAN to IGTVMIP were 0?86, 0?88, 1?06, respectively, which approached closest to 1. The CIs of IGTVPET2?0,IGTVPET2.5,IGTVPET20%,IGTVPETMAN and IGTVMIP which were 0?55, 0?56, 0?56, 0?54,0?55, respectively, were significantly larger than other CIs of IGTVPET and IGTVMIP (Z= -3?408-2?215,P <0?05). There were no statistical significance in the DIs of IGTVMIP and IGTVPET2.5,IGTVMIP and IGTVPET20%, IGTVMIP and IGTVPETMAN(0?77,0?82,0?71,0?67, 0?68,0?82,P>0?05). Conclusions The targets delineated based on SUV threshold setting of≥2?5, 20% of the SUVmax and manual contours on PET images correspond better with the target delineated on maximum intensity projection of 4D-CT images than other SUV thresholding methods.

Objective To compare the normal thickness of the esophageal wall measured by contrast?enhanced three?dimensional ( 3DCT ) , four?dimensional ( 4DCT ) , and cone beam computed tomography ( CBCT) ,and to provide a basis for target volume delineation in esophageal cancer. Methods From 2009 to 2016,thoracic contrast?enhanced 3DCT and 4DCT simulations were performed in 50 patients with lung cancer or metastatic lung cancer. Contrast?enhanced CBCT scans were acquired during the first three?dimensional conformal radiotherapy. The normal esophageal wall was contoured on 3DCT images, the end?exhalation phase of 4DCT images ( 4DCT50 ) , the maximum intensity projection of 4DCT images (4DCTMIP),and CBCT images. The wall thickness was measured on each segment and the average thickness of esophageal wall was obtained. Comparison of the thickness of a fixed segment of esophageal wall between different CT images was made by paired t test. Comparison of thickness on the same type of CT images between different segments of esophageal wall was made by one?way analysis of variance. Results For the thoracic and intra?abdominal segments,there was no significant difference in the thickness of esophageal wall between 3DCT and 4DCT50 images ( P= 0?056?0?550 );however, the thickness of esophageal wall was significantly smaller on 3DCT images than on 4DCTMIP or CBCT images (P=0?000?0?004).For the upper and middle thoracic segments,the thickness of esophageal wall was significantly larger on CBCT images than on 4DCTMIP images ( P= 0?008, P= 0?001 ) . On 3DCT, 4DCT50 , and 4DCTMIP images, the thickness of esophageal wall was significantly larger in the lower thoracic segment than in the upper or middle thoracic segments ( P=0.008~0?041);the intra?abdominal segment had a significantly larger thickness of esophageal wall than the thoracic segments ( all P=0?000 ) . There was no significant difference in wall thickness on CBCT images between three thoracic segments ( P=0.088~0?945) . Conclusions A uniform criterion can be adopted to judge the normal thickness of esophageal wall in gross tumor volume ( GTV ) delineation on 3DCT and 4DCT50 images for thoracic esophageal cancer. However,caution should be taken when 5 mm is used as a criterion for normal thickness of esophageal wall in GTV delineation on 4DCTMIP and CBCT images.

Objective:To evaluate the spatial position and functional parameters of 18F-FDG PET-CT and diffusion-weighted imaging (DWI) before and during radiotherapy (RT) based on the medium of 3DCT in patients with esophageal cancer and to explore whether the high-signal area derived from DWI can be used for individualized definition of the volume in need of dose-escalation for esophageal cancer. Methods:Thirty-two patients with esophageal cancer treated with concurrent chemoradiotherapy or neoadjuvant chemoradiation sequentially underwent repeated 3DCT, 18F-FDG PET-CT and enhanced MRI scans before RT and at the 15 th time of RT. All images were fused with the 3DCT images by deformable registration. The gross tumor volume (GTV) was delineated based on PET Edge on the first and second 3DCT, PET-CT and DWI and corresponding T 2-weighted MRI (T 2W-MRI) fused images, and defined as GTV CTpre and GTV CTdur, GTV PETpre, GTV PETdur, GTV DWIpre and GTV DWIdur, respectively. SUV (SUV max, SUV mean, SUV peak), MTV, TLG, ADC (ADC min and ADC mean) values and △SUV (△SUV max, △SUV mean, △SUV peak), △MTV, △TLG, △ADC (△ADC mean and △ADC min) of lesions were measured before and during RT. Results:The differences in SUV (SUV max, SUV mean, SUV peak), MTV, TLG, ADC mean and ADC min of the GTV before and during RT were statistically significant (all P<0.001). The tumor ADC and SUV values before and during RT showed no significant correlation, and there was no correlation between △ADC and △SUV (both P>0.05). The conformity index (CI) of GTV PETpre to GTV DWIpre was significantly higher than that of GTV PETdur to GTV DWIdur ( P<0.001). The shrinkage rate of maximum diameter (△LD DWI)(24%) and the shrinkage rate of tumor volume (VRR DWI)(60%) based on DWI during RT were significantly greater than the corresponding PET-based △LD PET (14%) and VRR PET (41%)( P=0.017 and P<0.001). Conclusions:The location of high residual FDG uptake based on PET-CT yields poor spatial matching compared with the area with residual high signal based on DWI during RT. Tumor ADC and SUV values may play complementary roles as imaging markers for prediction of patterns of failure and for definition of the volume in need of dose-escalation. In addition, the shrinkage rates of tumor maximum diameter/volume based on DWI during RT are significantly faster than those based on PET-CT. Therefore, the feasibility of selecting boosting of the high signal area derived from DWI for individualized definition of the volume for esophageal cancer is not clear.

Objective:To investigate the application value of 18F-FDG PET-CT combined with MRI in the radiotherapy for esophageal carcinoma by comparing the differences in the gross target volume (GTV), position length delineated on the end expiratory (EE) phase of 4DCT, PET-CT and T 2-weighted MRI (T 2W-MRI). Methods:Twenty-six patients with thoracic esophageal cancer scheduled to receive concurrent chemoradiotherapy sequentially underwent 3DCT, 4DCT, PET-CT and enhanced MRI for thoracic localization. All images were fused with the 3DCT images by deformable registration. GTV CT, GTV 50% GTV PET2.5, GTV MRI and GTV DWI were delineated on 3DCT, the EE phase of 4DCT images, PET-CT with the thresholds of SUV≥2.5, T 2W-MRI and diffusion-weighted images, respectively. Results:GTV PET2.5 was significantly larger than GTV 50% and GTV MRI ( P<0.001 and P=0.008), whereas the volume of GTV MRI was similar to that of GTV 50%( P=0.439). Significant differences were observed between the CI of GTV MRI to GTV 50% and GTV PET2.5 to GTV 50%( P=0.004). The conformity indexes (CIs) of GTV MRI to GTV CT and GTV PET2.5 to GTV CT were statistically significant ( P=0.004 and P=0.039). The CI of GTV MRI to GTV PET2.5 was significantly smaller than that of GTV MRI to GTV 50%, GTV MRI to GTV CT, GTV PET2.5 to GTV 50% and GTV PET2.5 to GTV CT ( P=0.000-0.021). The length of gastroscopy was similar to those of GTV PET2.5 and GTV DWI (both P>0.05), and there was no significant difference in the length between GTV PET2.5 and GTV DWI ( P=0.072). Conclusion:GTV MRI yields significantly different volume and poor spatial matching compared with GTV PET2.5. The application of PET-CT combined with MRI under respiratory gating system in the delineation of GTV should be used with caution in thoracic squamous esophageal cancer. MRI-DWI can replace PET-CT to help determine the upper and lower boundaries of GTV based on CT images.

Objective To compare the geometric differences of gross tumor volumes(GTV)and displacements of selected clips propagated by rigid image registration(RIR)and deformable image registration (DIR)at end-inhale phase(CT0)and end-exhale phase(CT50)based on four-dimensional computed tomography(4DCT)of the whole breast after breast-conserving surgery(BCS). Methods Forty-four patients who underwent 4DCT simulation scans after BCS were selected. The GTV and displacements of selected metal clips at CT0and CT50were manually delineated by the same radiotherapy physician. Subsequently,the GTV and displacements of selected clips from CT0images were transformed and propagated to CT50images using RIR and DIR.The geometric differences of GTV and displacements of surgical clips from DIR were compared with those from RIR based on the dice similarity coefficient(DSC)and the displacements of the center of mass(COM)in the three-dimensional(3D)directions. Results The mean DSC was 0.86± 0.04 for RIR and 0.87± 0.04 for DIR(P=0.000).The displacements of COM in 3D directions from RIR were significantly greater than those from DIR(1.22 mm vs. 1.10 mm,P=0.000).In the anterior-posterior direction,the displacements from RIR were significantly greater than those from DIR for both GTV and selected clips(P=0.000).However,in the left-right and superior-inferior directions,there were no significant differences in displacements between RIR and DIR for both GTV and the selected clips(all P>0.05). Conclusions DIR can improve the overlap for GTV registration from 4DCT scans at CT0and CT50.Furthermore,DIR is superior to RIR in reflecting GTV and the displacements of selected clips in anterior-posterior direction induced by respiratory movement.

Objective To detect the changes of heart volume during concurrent chemoradiotherapy for esophageal cancer based on repeated enhanced 4DCT.Methods Patients with squamous cell esophageal cancer underwent repeated enhanced 4DCT and 3DCT scans before and after 10,20 and 30 fractions of radiotherapy,respectively.The heart was contoured on 3DCT,end expiratory (EE) and maximum intensity projection (MIP) of 4DCTimages.The changes in theheart volume,blood pressure.and heart rate were statistically compared at different time points.Results A total of forty-six patients completed 4 fractions of 3DCT and enhanced 4DCT scans.Compared with the initial values,the heart volume was significantly decreased by 3.27％,4.45％ and 4.52％ after 10 fractions of radiotherapy,and reduced by 6.05％,5.64％ and 4.51％ following 20 fractions of radiotherapy on 3DCT,EE and MIP,respectively (P=0.000-0.027).The heart volume after 30 fractions of radiotherapy did not significantly differ from the initial volume (P＞ 0.05).After radiotherapy,there was a significant decrease inboth systolic and diastolic blood pressure (P =0.000 and P =0.009) and a significant ‖ increase in the heart rate (P=0.0 0 1) compared with those measured before radiotherapy.Conclusions Enhanced 4DCT scan can clearly reflect the changes of heart volume throughout concurrent chemoradiotherapy.The heart volume starts to shrink during the early stage of radiotherapy and continue to decrease until the middleand late-stage,whereas it restores to the initial volume after radiotherapy.Simultaneously,blood pressure declines and heart rate is accelerated during radiotherapy.