Early, non-invasive detection of radiation-induced lung injury using PET/CT by targeting CXCR4.

PURPOSE: Radiation-induced lung injury (RILI) is a severe side effect of radiotherapy (RT) for thoracic malignancies and we currently lack established methods for the early detection of RILI. In this study, we synthesized a new tracer, [18F]AlF-NOTA-QHY-04, targeting C-X-C-chemokine-receptor-type-4 (CXCR4) and investigated its feasibility to detect RILI. METHODS: An RILI rat model was constructed and scanned with [18F]AlF-NOTA-QHY-04 PET/CT and [18F]FDG PET/CT periodically after RT. Dynamic, blocking, autoradiography, and histopathological studies were performed on the day of peak uptake. Fourteen patients with radiation pneumonia, developed during or after thoracic RT, were subjected to PET scan using [18F]AlF-NOTA-QHY-04. RESULTS: The yield of [18F]AlF-NOTA-QHY-04 was 28.5-43.2%, and the specific activity was 27-33 GBq/µmol. [18F]AlF-NOTA-QHY-04 was mainly excreted through the kidney. Significant increased [18F]AlF-NOTA-QHY-04 uptake in the irradiated lung compared with that in the normal lung in the RILI model was observed on day 6 post-RT and peaked on day 14 post-RT, whereas no apparent uptake of [18F]FDG was shown on days 7 and 15 post-RT. MicroCT imaging did not show pneumonia until 42 days post-RT. Significant intense [18F]AlF-NOTA-QHY-04 uptake was confirmed by autoradiography. Immunofluorescence staining demonstrated expression of CXCR4 was significantly increased in the irradiated lung tissue, which correlated with results obtained from hematoxylin-eosin and Masson's trichrome staining. In 14 patients with radiation pneumonia, maximum standardized uptake values (SUVmax) were significantly higher in the irradiated lung compared with those in the normal lung. SUVmax of patients with grade 2 RILI was significantly higher than that of patients with grade 1 RILI. CONCLUSION: This study indicated that [18F]AlF-NOTA-QHY-04 PET/CT imaging can detect RILI non-invasively and earlier than [18F]FDG PET/CT in a rat model. Clinical studies verified its feasibility, suggesting the clinical potential of [18F]AlF-NOTA-QHY-04 as a PET/CT tracer for early monitoring of RILI.

Inter-Observer and Intra-Observer Variability in Gross Tumor Volume Delineation of Primary Esophageal Carcinomas Based on Different Combinations of Diagnostic Multimodal Images.

Background and Purpose: This study aimed to investigate inter-/intra-observer delineation variability in GTVs of primary esophageal carcinomas (ECs) based on planning CT with reference to different combinations of diagnostic multimodal images from endoscopy/EUS, esophagography and FDG-PET/CT. Materials and Methods: Fifty patients with pathologically proven thoracic EC who underwent diagnostic multimodal images before concurrent chemoradiotherapy were enrolled. Five radiation oncologist independently delineated the GTVs based on planning CT only (GTVC), CT combined with endoscopy/EUS (GTVCE), CT combined with endoscopy/EUS and esophagography (X-ray) (GTVCEX), and CT combined with endoscopy/EUS, esophagography, and FDG-PET/CT (GTVCEXP). The intra-/inter-observer variability in the volume, longitudinal length, generalized CI (CIgen), and position of the GTVs were assessed. Results: The intra-/inter-observer variability in the volume and longitudinal length of the GTVs showed no significant differences (p>0.05). The mean intra-observer CIgen values for all observers was 0.73 ± 0.15. The mean inter-observer CIgen values for the four multimodal image combinations was 0.67 ± 0.11. The inter-observer CIgen for the four combined images was the largest, showing significant differences with those for the other three combinations. The intra-observer CIgen among different observers and inter-observer CIgen among different combinations of multimodal images showed significant differences (p<0.001). The intra-observer CIgen for the senior radiotherapists was larger than that for the junior radiotherapists (p<0.001). Conclusion: For radiation oncologists with advanced medical imaging training and clinical experience, using diagnostic multimodal images from endoscopy/EUS, esophagography, and FDG-PET/CT could reduce the intra-/inter-observer variability and increase the accuracy of target delineation in primary esophageal carcinomas.

Comparison of the Gross Target Volumes Based on Diagnostic PET/CT for Primary Esophageal Cancer.

BACKGROUND: Clinically, many esophageal cancer patients who planned for radiation therapy have already undergone diagnostic Positron-emission tomography/computed tomography (PET/CT) imaging, but it remains unclear whether these imaging results can be used to delineate the gross target volume (GTV) of the primary tumor for thoracic esophageal cancer (EC). METHODS: Seventy-two patients diagnosed with thoracic EC had undergone prior PET/CT for diagnosis and three-dimensional CT (3DCT) for simulation. The GTV3D was contoured on the 3DCT image without referencing the PET/CT image. The GTVPET-ref was contoured on the 3DCT image referencing the PET/CT image. The GTVPET-reg was contoured on the deformed registration image derived from 3DCT and PET/CT. Differences in the position, volume, length, conformity index (CI), and degree of inclusion (DI) among the target volumes were determined. RESULTS: The centroid distance in the three directions between two different GTVs showed no significant difference (P > 0.05). No significant difference was found among the groups in the tumor volume (P > 0.05). The median DI values of the GTVPET-reg and GTVPET-ref in the GTV3D were 0.82 and 0.86, respectively (P = 0.006). The median CI values of the GTV3D in the GTVPET-reg and GTVPET-ref were 0.68 and 0.72, respectively (P = 0.006). CONCLUSIONS: PET/CT can be used to optimize the definition of the target volume in EC. However, no significant difference was found between the GTVs delineated based on visual referencing or deformable registration whether using the volume or position. So, in the absence of planning PET-CT images, it is also feasible to delineate the GTV of primary thoracic EC with reference to the diagnostic PET-CT image.

Geometrical Comparison and Quantitative Evaluation of 18F-FDG PET/CT- and DW-MRI-Based Target Delineation Before and During Radiotherapy for Esophageal Squamous Carcinoma.

BACKGROUND AND PURPOSE: This study aimed to evaluate the geometrical differences in and metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) performed before and during radiotherapy (RT) for patients with esophageal cancer based on the three-dimensional CT (3DCT) medium and explore whether the high signal area derived from DW-MRI can be used as a tool for an individualized definition of the volume in need of dose escalation for esophageal squamous cancer. MATERIALS AND METHODS: Thirty-two patients with esophageal squamous cancer sequentially underwent repeated 3DCT, 18F-FDG PET-CT, and enhanced MRI before the initiation of RT and after the 15th fraction. All images were fused with 3DCT images through deformable registration. The gross tumor volume (GTV) was delineated based on PET Edge on the first and second PET-CT images and defined as GTVPETpre and GTVPETdur, respectively. GTVDWIpre and GTVDWIdur were delineated on the first and second DWI and corresponding T2-weighted MRI (T2W-MRI)-fused images. The maximum, mean, and peak standardized uptake values (SUVs; SUVmax, SUVmean, and SUVpeak, respectively); metabolic tumor volume (MTV); and total lesion glycolysis(TLG) and its relative changes were calculated automatically on PET. Similarly, the minimum and mean apparent diffusion coefficient (ADC; ADCmin and ADCmean) and its relative changes were measured manually using ADC maps. RESULTS: The volume of GTVCT exhibited a significant positive correlation with that of GTVPET and GTVDWI (both p < 0.001). Significant differences were observed in both ADCs and 18F-FDG PET metabolic parameters before and during RT (both p < 0.001). No significant correlation was observed between SUVs and ADCs before and during RT (p = 0.072-0.944) and between ∆ADCs and ∆SUVs (p = 0.238-0.854). The conformity index and degree of inclusion of GTVPETpre to GTVDWIpre were significantly higher than those of GTVPETdur to GTVDWIdur (both p < 0.001). The maximum diameter shrinkage rate (∆LDDWI) (24%) and the tumor volume shrinkage rate (VRRDWI) (60%) based on DW-MRI during RT were significantly greater than the corresponding PET-based ∆LDPET (14%) and VRRPET (41%) rates (p = 0.017 and 0.000, respectively). CONCLUSION: Based on the medium of CT images, there are significant differences in spatial position, biometabolic characteristics, and the tumor shrinkage rate for GTVs derived from 18F-FDG PET-CT and DW-MRI before and during RT for esophageal squamous cancer. Further studies are needed to determine if DW-MRI will be used as tool for an individualized definition of the volume in need of dose escalation.

Using CT texture analysis to differentiate between peripheral lung cancer and pulmonary inflammatory pseudotumor.

BACKGROUND: This study is to distinguish peripheral lung cancer and pulmonary inflammatory pseudotumor using CT-radiomics features extracted from PET/CT images. METHODS: In this study, the standard 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (18 F-FDG PET/CT) images of 21 patients with pulmonary inflammatory pseudotumor (PIPT) and 21 patients with peripheral lung cancer were retrospectively collected. The dataset was used to extract CT-radiomics features from regions of interest (ROI), The intra-class correlation coefficient (ICC) was used to screen the robust feature from all the radiomic features. Using, then, statistical methods to screen CT-radiomics features, which could distinguish peripheral lung cancer and PIPT. And the ability of radiomics features distinguished peripheral lung cancer and PIPT was estimated by receiver operating characteristic (ROC) curve and compared by the Delong test. RESULTS: A total of 435 radiomics features were extracted, of which 361 features showed relatively good repeatability (ICC ≥ 0.6). 20 features showed the ability to distinguish peripheral lung cancer from PIPT. these features were seen in 14 of 330 Gray-Level Co-occurrence Matrix features, 1 of 49 Intensity Histogram features, 5 of 18 Shape features. The area under the curves (AUC) of these features were 0.731 ± 0.075, 0.717, 0.748 ± 0.038, respectively. The P values of statistical differences among ROC were 0.0499 (F9, F20), 0.0472 (F10, F11) and 0.0145 (F11, Mean4). The discrimination ability of forming new features (Parent Features) after averaging the features extracted at different angles and distances was moderate compared to the previous features (Child features). CONCLUSION: Radiomics features extracted from non-contrast CT based on PET/CT images can help distinguish peripheral lung cancer and PIPT.

Comparison of gross target volumes based on four-dimensional CT, positron emission tomography-computed tomography, and magnetic resonance imaging in thoracic esophageal cancer.

PURPOSE: The application value of 18 F-FDG PET-CT combined with MRI in the radiotherapy of esophageal carcinoma was discussed by comparing the differences in position, volume, and the length of GTVs delineated on the end-expiration (EE) phase of 4DCT, 18 F-FDG PET-CT, and T2 W-MRI. METHODS: A total of 26 patients with thoracic esophageal cancer sequentially performed 3DCT, 4DCT, 18 F-FDG PET-CT, and MRI simulation for thoracic localization. All images were fused with the 3DCT images by deformable registration. GTVCT and GTV50% were delineated on 3DCT and the EE phase of 4DCT images, respectively. The GTV based on PET-CT images was determined by thresholds of SUV ≥ 2.5 and designated as GTVPET2.5 . The images of T2 -weighted sequence and diffusion-weighted sequence were referred as GTVMRI and GTVDWI , respectively. The length of the abnormality seen on the 4DCT, PET-CT, and DWI was compared. RESULTS: GTVPET2.5 was significantly larger than GTV50% and GTVMRI (P = .000 and 0.008, respectively), and the volume of GTVMRI was similar to that of GTV50% (P = .439). Significant differences were observed between the CI of GTVMRI to GTV50% and GTVPET2.5 to GTV50% (P = .004). The CI of GTVMRI to GTVCT and GTVPET2.5 to GTVCT were statistically significant (P = .039). The CI of GTVMRI to GTVPET2.5 was significantly lower than that of GTVMRI to GTV50% , GTVMRI to GTVCT , GTVPET2.5 to GTV50% , and GTVPET2.5 to GTVCT (P = .000-0.021). Tumor length measurements by endoscopy were similar to the tumor length as measured by PET and DWI scan (P > .05), and there was no significant difference between the longitudinal length of GTVPET2.5 and GTVDWI (P = .072). CONCLUSION: The volumes of GTVMRI and GTV50% were similar. However, GTVMRI has different volumes and poor spatial matching compared with GTVPET2.5 .The MRI imaging could not include entire respiration. It may be a good choice to guide target delineation and construction of esophageal carcinoma by combining 4DCT with MRI imaging. Utilization of DWI in treatment planning for esophageal cancer may provide further information to assist with target delineation. Further studies are needed to determine if this technology will translate into meaningful differences in clinical outcome.

Changes in cardiac volume determined with repeated enhanced 4DCT during chemoradiotherapy for esophageal cancer.

BACKGROUND: Concurrent chemoradiotherapy is considered curative intent treatment for patients with non-operative esophageal cancer. Radiation-induced heart damage receives much attention. We performed repeated four-dimensional computed tomography (4DCT) to detect changes in cardiac volume during radiotherapy for esophageal cancer patients, and explored potential factors responsible for those changes. METHODS: Forty-six patients with esophageal cancer underwent enhanced 4DCT and three-dimensional (3D) CT scans before radiotherapy and every 10 fractions during treatment. The heart was contoured on 3DCT images, 4DCT end expiratory (EE) images and 4DCT maximum intensity projection (MIP) images by the same radiation oncologist. Heart volumes and other relative parameters were compared by the SPSS software package, version 19.0. RESULTS: Compared with its initial value, heart volume was smaller at the 10th fraction (reduction = 3.27%, 4.45% and 4.52% on 3DCT, EE and MIP images, respectively, p < 0.05) and the 20th fraction (reduction = 6.05%, 5.64% and 4.51% on 3DCT, EE and MIP images, respectively, p < 0.05), but not at the 30th fraction. Systolic and diastolic blood pressures were reduced (by 16.95 ± 16.69 mmHg and 7.14 ± 11.64 mmHg, respectively, both p < 0.05) and the heart rate was elevated by 5.27 ± 6.25 beats/min (p < 0.05) after radiotherapy. None of the potential explanatory variables correlated with heart volume changes. CONCLUSIONS: Cardiac volume reduced significantly from an early treatment stage and maintained the reduction until the middle stage. The heart volume changes observed on 3DCT and 4DCT were consistent during radiotherapy. The changes in heart volume, blood pressure and heart rate may be valuable indicators of cardiac impairment and target dose changes.

Comparison of gross tumor volume of primary oesophageal cancer based on contrast-enhanced three-dimensional, four-dimensional, and cone beam computed tomography.

BACKGROUND: To explore motion information included in 3DCT, 4DCT and CBCT by comparing volumetric and positional differences of GTV. RESULTS: Independent of tumor location, significant differences were observed among volumes [IGTV10 > (IGTVCBCT or IGTVMIP) > (GTV3D or GTV4D50)]. The underestimations or overestimations between IGTV10 and IGTVCBCT were larger than those between IGTV10 and IGTVMIP (p < 0.001-0.011; p < 0.001-0.023). For upper oesophageal tumors, GTV4D50/IGTVCBCT negatively correlated with motion vector (r = -0.756, p = 0.011). In AP direction, the centroid coordinates of IGTVCBCT differed from GTV3D, GTV4D50, IGTVMIP and IGTV10 (p = 0.006, 0.013, 0.038, and 0.010). For middle oesophageal tumors, IGTV10/IGTVCBCT positively correlated with motion vector (r = 0.695, p = 0.006). The centroid coordinates of IGTVCBCT differed from those of IGTV10 (p = 0.046) in AP direction. For distal oesophageal tumors, the centroid coordinates of IGTVCBCT showed significant differences to those of IGTVMIP (p = 0.042) in LR direction. For both middle and distal tumors, the degrees of associations of IGTV10 outside IGTVCBCT significantly correlated with the motion vector (r = 0.540, p = 0.046; r = 0.678, p = 0.031). MATERIALS AND METHODS: Thirty-four oesophageal cancer patients underwent 3DCT, 4DCT and CBCT. GTV3D, GTV4D50, internal GTVMIP (IGTVMIP) and IGTVCBCT were delineated on 3DCT, 4DCT50, 4DCTMIP and CBCT. GTVs from 10 respiratory phases were combined to produce GTV10. Differences in volume, position for different targets, correlation between volume ratio and motion vector were evaluated. The motion vector was the spatial moving of the target centroid position. CONCLUSIONS: IGTVCBCT encompasses more motion information than GTV3D and GTV4D50 for upper oesophageal tumors, but slightly less than IGTV10 for middle and distal oesophageal tumors. IGTVCBCT incorporated similar motion information to IGTVMIP. However, motion information encompassed in CBCT and MIP cannot replace each other.

A comparative study of target volumes based on 18F-FDG PET-CT and ten phases of 4DCT for primary thoracic squamous esophageal cancer.

PURPOSE: To investigate the correlations in target volumes based on 18F-FDG PET/CT and four-dimensional CT (4DCT) to detect the feasibility of implementing PET in determining gross target volumes (GTV) for tumor motion for primary thoracic esophageal cancer (EC). METHODS: Thirty-three patients with EC sequentially underwent contrast-enhanced 3DCT, 4DCT, and 18F-FDG PET-CT thoracic simulation. The internal gross target volume (IGTV)10 was obtained by combining the GTV from ten phases of 4DCT. The GTVs based on PET/CT images were defined by setting of different standardized uptake value thresholds and visual contouring. The difference in volume ratio, conformity index (CI), and degree of inclusion (DI) between IGTV10 and GTVPET was compared. RESULTS: The images from 20 patients were suitable for further analysis. The optimal volume ratio of 0.95±0.32, 1.06±0.50, 1.07±0.49 was at standardized uptake value (SUV)2.5, SUV20%, or manual contouring. The mean CIs were from 0.33 to 0.54. The best CIs were at SUV2.0 (0.51±0.11), SUV2.5 (0.53±0.13), SUV20% (0.53±0.12), and manual contouring (0.54±0.14). The mean DIs of GTVPET in IGTV10 were from 0.60 to 0.90, and the mean DIs of IGTV10 in GTVPET ranged from 0.35 to 0.78. A negative correlation was found between the mean CI and different SUV (P=0.000). CONCLUSION: None of the PET-based contours had both close spatial and volumetric approximation to the 4DCT IGTV10. Further evaluation and optimization of PET as a tool for target identification are required.

Comparative evaluation of target volumes defined by deformable and rigid registration of diagnostic PET/CT to planning CT in primary esophageal cancer.

BACKGROUND: To evaluate the geometrical differences of target volumes propagated by deformable image registration (DIR) and rigid image registration (RIR) to assist target volume delineation between diagnostic Positron emission tomography/computed tomography (PET/CT) and planning CT for primary esophageal cancer (EC). METHODS: Twenty-five patients with EC sequentially underwent a diagnostic F-fluorodeoxyglucose (F-FDG) PET/CT scan and planning CT simulation. Only 19 patients with maximum standardized uptake value (SUVmax) ≥ 2.0 of the primary volume were available. Gross tumor volumes (GTVs) were delineated using CT and PET display settings. The PET/CT images were then registered with planning CT using MIM software. Subsequently, the PET and CT contours were propagated by RIR and DIR to planning CT. The properties of these volumes were compared. RESULTS: When GTVCT delineated on CT of PET/CT after both RIR and DIR was compared with GTV contoured on planning CT, significant improvements using DIR were observed in the volume, displacements of the center of mass (COM) in the 3-dimensional (3D) direction, and Dice similarity coefficient (DSC) (P = 0.003; 0.006; 0.014). Although similar improvements were not observed for the same comparison using DIR for propagated PET contours from diagnostic PET/CT to planning CT (P > 0.05), for DSC and displacements of COM in the 3D direction of PET contours, the DIR resulted in the improved volume of a large percentage of patients (73.7%; 68.45%; 63.2%) compared with RIR. For diagnostic CT-based contours or PET contours at SUV2.5 propagated by DIR with planning CT, the DSC and displacements of COM in 3D directions in the distal segment were significantly improved compared to the upper and middle segments (P > 0.05). CONCLUSION: We observed a trend that deformable registration might improve the overlap for gross target volumes from diagnostic PET/CT to planning CT. The distal EC might benefit more from DIR.

Comparison of rigid and deformable registration through the respiratory phases of four-dimensional computed tomography image data sets for radiotherapy after breast-conserving surgery.

BACKGROUND: The aim of this study was to compare the geometric differences in gross tumor volume (GTV) and surgical clips propagated by rigid image registration (RIR) and deformable image registration (DIR) using a four-dimensional computed tomography (4DCT) image data set for patients treated with boost irradiation or accelerated partial breast irradiation after breast-conserving surgery (BCS). METHODS: The 4DCT data sets of 44 patients who had undergone BCS were acquired. GTV and selected clips were manually delineated on end-inhalation phase (CT0) and end-exhalation phase (CT50) images of 4DCT data sets. Subsequently, the GTV and selected clips from CT0 images were transformed and propagated to CT50 images using RIR and DIR, respectively. The geometric differences in GTV and surgical clips from DIR were compared with those of RIR. RESULTS: The mean Dice similarity coefficient (DSC) index was 0.860 ±â€Š0.042 for RIR and 0.870 ±â€Š0.040 for DIR for GTV (P = .000). The three-dimensional distance to the center of mass (COM) of the GTV from RIR was longer than that from DIR (1.22 mm and 1.10 mm, respectively, P = .000). Moreover, in the anterior-posterior direction, displacements from RIR were significantly greater than those from DIR for both GTV (0.70 mm and 0.50 mm, respectively) and selected clips (upper clip, 0.45 mm vs 0.20 mm; inner clip, 0.55 mm vs 0.30 mm; outer clip, 0.40 mm vs 0.20 mm; lower clip, 0.50 mm vs 0.25 mm) (P = .000). However, in the left-right and superior-inferior directions, there were no significant displacement differences between RIR and DIR for GTV and the selected clips (all P > .050). CONCLUSION: DIR can improve the overlap for GTV registration from CT0 to CT50 images from 4DCT scanning. Furthermore, DIR is superior to RIR in reflecting the displacement of GTV and selected clips in the anterior-posterior direction induced by respiratory movement.

Interobserver variability in the delineation of the tumour bed using seroma and surgical clips based on 4DCT scan for external-beam partial breast irradiation.

BACKGROUND: To explore the interobserver variability in the delineation of the tumour bed using seroma and surgical clips based on the four-dimensional computed tomography (4DCT) scan for external-beam partial breast irradiation (EB-PBI) during free breathing. METHODS: Patients with a seroma clarity score (SCS) 3 ~ 5 and ≥5 surgical clips in the lumpectomy cavity after breast-conserving surgery who were recruited for EB-PBI underwent 4DCT simulation. Based on the ten sets of 4DCT images acquired, the tumour bed formed using the clips, the seroma, and both the clips and seroma (defined as TBC, TBS and TBC+S, respectively) were delineated by five radiation oncologists using specific guidelines. The following parameters were calculated to analyse interobserver variability: volume of the tumour bed (TBC, TBS, TBC+S), coefficient of variation (COVC, COVS, COVC+S), and matching degree (MDC, MDS, MDC+S). RESULTS: The interobserver variability for TBC and TBC+S and for COVC and COVC+S were statistically significant (p = 0.021, 0.008, 0.002, 0.015). No significant difference was observed for TBS and COVS (p = 0.867, 0.061). Significant differences in interobserver variability were observed for MDC vs MDS, MDC vs MDC+S, MDS vs MDC+S (p = 0.000, 0.032, 0.008), the interobserver variability of MDS was smaller than that of MDC and MDC+S (MDS > MDC+S > MDC). CONCLUSIONS: When the SCS was 3 ~ 5 points and the number of surgical clips was ≥5, interobserver variability was minimal for the delineation of the tumour bed based on seroma.

Comparison of primary tumour volumes delineated on four-dimensional computed tomography maximum intensity projection and (18) F-fluorodeoxyglucose positron emission tomography computed tomography images of non-small cell lung cancer.

INTRODUCTION: The study aims to compare the positional and volumetric differences of tumour volumes based on the maximum intensity projection (MIP) of four-dimensional CT (4DCT) and (18) F-fluorodexyglucose ((18) F-FDG) positron emission tomography CT (PET/CT) images for the primary tumour of non-small cell lung cancer (NSCLC). METHODS: Ten patients with NSCLC underwent 4DCT and (18) F-FDG PET/CT scans of the thorax on the same day. Internal gross target volumes (IGTVs) of the primary tumours were contoured on the MIP images of 4DCT to generate IGTVMIP . Gross target volumes (GTVs) based on PET (GTVPET ) were determined with nine different threshold methods using the auto-contouring function. The differences in the volume, position, matching index (MI) and degree of inclusion (DI) of the GTVPET and IGTVMIP were investigated. RESULTS: In volume terms, GTVPET 2.0 and GTVPET 20% approximated closely to IGTVMIP with mean volume ratio of 0.93 ± 0.45 and 1.06 ± 0.43, respectively. The best MI was between IGTVMIP and GTVPET 20% (0.45 ± 0.23). The best DI of IGTVMIP in GTVPET was IGTVMIP in GTVPET 20% (0.61 ± 0.26). CONCLUSIONS: In 3D PET images, the GTVPET contoured by standardised uptake value (SUV) 2.0 or 20% of maximal SUV (SUVmax ) approximate closely to the IGTVMIP in target size, while the spatial mismatch is apparent between them. Therefore, neither of them could replace IGTVMIP in spatial position and form. The advent of 4D PET/CT may improve the accuracy of contouring the perimeter for moving targets.

Comparative evaluation of CT-based and PET/4DCT-based planning target volumes in the radiation of primary esophageal cancer.

PURPOSE: To compare planning target volume (PTV) defined by PET combined with 4DCT to 3DCT and 4DCT. METHODS: Eighteen (18/30) esophageal cancer patients who underwent 3DCT, 4DCT and (18)F-FDG PET-CT thoracic simulation with SUVmax≥2.0 of the primary volume were enrolled. CTV3D was formed on 3DCT by adding a margin of 30 mm in cranial-caudal direction and 5 mm in transversal direction. PTV3D was defined using a 10 mm margin to CTV3D and CTV4D was obtained by fusion of CTV from ten phases of 4DCT. A 5 mm margin for setup errors to CTV4D was to form PTV4D. BTVPET was generated with the assumption that motion was captured in PET images using a thresholding methods: 20% SUVmax. CTV(PET) 4DCT was calculated by the union of BTVPET and CTV4D, and a 5 mm margin to CTV(PET) 4DCT was used to form PTV(PET) 4DCT. The geometrical differences of the targets were evaluated. RESULTS: Statistically significant differences were observed among CTV3D, CTV4D and CTV(PET) 4DCT (CTV(PET) 4DCT>CTV4D>CTV3D, P=0.000-0.038). PTV3D, PTV4D, and PTV(PET) 4DCT also differed significantly from each other (PTV(PET) 4DCT>PTV4D>PTV3D, P=0.000-0.048). The DI of PTV3D in PTV(PET) 4DCT was significantly larger than that of PTV3D in PTV 4D (P=0.042). There were no significant differences between the DI of PTV4D in PTV3D and PTV(PET) 4DCT in PTV3D (P=0.118). CONCLUSIONS: As demonstrated by the assessment of the geometrical differences in PET/4DCT-based and 3DCT-based PTV, PET/4DCT could affect not only the volume of PTV but also its shape.

Dosimetric impact of tumor bed delineation variability based on 4DCT scan for external-beam partial breast irradiation.

This study sought to evaluate the dosimetric impact of tumor bed delineation variability (based on clips, seroma or both clips and seroma) during external-beam partial breast irradiation (EB-PBI) planned utilizing four-dimensional computed tomography (4DCT) scans. 4DCT scans of 20 patients with a seroma clarity score (SCS) 3~5 and ≥5 surgical clips were included in this study. The combined volume of the tumor bed formed using clips, seroma, or both clips and seroma on the 10 phases of 4DCT was defined as the internal gross target volume (termed IGTVC, IGTVS and IGTVC+S, respectively). A 1.5-cm margin was added by defining the planning target volume (termed PTVC, PTVS and PTVC+S, respectively). Three treatment plans were established using the 4DCT images (termed EB-PBIC, EB-PBIS, EB-PBIC+S, respectively). The results showed that the volume of IGTVC+S was significantly larger than that of IGTVCand IGTVS. Similarly, the volume of PTVC+S was markedly larger than that of PTVC and PTVS. However, the PTV coverage for EB-PBIC+S was similar to that of EB-PBIC and EB-PBIS, and there were no significant differences in the homogeneity index or conformity index between the three treatment plans (P=0.878, 0.086). The EB-PBIS plan resulted in the lowest ipsilateral normal breast and ipsilateral lung doses compared with the EB-PBIC and EB-PBIC+S plans. To conclude, the volume variability delineated based on clips, seroma or both clips and seroma resulted in dosimetric variability for organs at risk, but did not show a marked influence on the dosimetric distribution.

Comparison of primary target volumes delineated on four-dimensional CT and 18 F-FDG PET/CT of non-small-cell lung cancer.

BACKGROUND: To determine the optimal threshold of 18 F-fluorodexyglucose (18 F-FDG) positron emission tomography CT (PET/CT) images that generates the best volumetric match to internal gross target volume (IGTV) based on four-dimensional CT (4DCT) images. METHODS: Twenty patients with non-small cell lung cancer (NSCLC) underwent enhanced three-dimensional CT (3DCT) scan followed by enhanced 4DCT scan of the thorax under normal free breathing with the administration of intravenous contrast agents. A total of 100 ml of ioversol was injected intravenously, 2 ml/s for 3DCT and 1 ml/s for 4DCT. Then 18 F-FDG PET/CT scan was performed based on the same positioning parameters (the same immobilization devices and identical position verified by laser localizer as well as skin marks). Gross target volumes (GTVs) of the primary tumor were contoured on the ten phases images of 4DCT to generate IGTV10. GTVPET were determined with eight different threshold using an auto-contouring function. The differences in the position, volume, concordance index (CI) and degree of inclusion (DI) of the targets between GTVPET and IGTV10 were compared. RESULTS: The images from seventeen patients were suitable for further analysis. Significant differences between the centric coordinate positions of GTVPET (excluding GTVPET15%) and IGTV10 were observed only in z axes (P < 0.05). GTVPET15%, GTVPET25% and GTVPET2.0 were not statistically different from IGTV10 (P < 0.05). GTVPET15% approximated closely to IGTV10 with median percentage volume changes of 4.86%. The best CI was between IGTV10 and GTVPET15% (0.57). The best DI of IGTV10 in GTVPET was IGTV10 in GTVPET15% (0.80). CONCLUSION: None of the PET-based contours had both close spatial and volumetric approximation to the 4DCT IGTV10. At present 3D-PET/CT should not be used for IGTV generation.