Pretreatment PET/CT imaging of angiogenesis based on 18F-RGD tracer uptake may predict antiangiogenic response.

PURPOSE: To explore the relationship between metabolic uptake of the 18F-ALF-NOTA-PRGD2 (18F-RGD) tracer on positron emission tomography/computerized tomography (PET/CT) and the antiangiogenic effect of apatinib in patients with solid malignancies. MATERIALS AND PATIENTS: Patients with measurable lesions scheduled for second- or third-line single-agent therapy with apatinib were eligible for this prospective clinical trial. All patients underwent 18F-RGD PET/CT examination before the start of treatment. Standardized uptake values (SUVs) of contoured tumor lesions were computed and compared using independent sample t-tests or the Mann-Whitney U test. Receiver-operating characteristic (ROC) curve analysis was used to determine accuracy in predicting response. Survival curves were compared using the Kaplan-Meier method. RESULTS: Of 38 patients who consented to study participation, 25 patients with 42 measurable lesions met the criteria for inclusion in this response assessment analysis. The median follow-up time was 3 months (range, 1-10 months), and the median progression-free survival (PFS) was 3 months (95% confidence interval, 1.04-4.96). The SUVpeak and SUVmean were significantly higher in responding tumors than in non-responding tumors (4.98 ± 2.34 vs 3.59 ± 1.44, p = 0.048; 3.71 ± 1.15 vs 2.95 ± 0.49, P = 0.036). SUVmax did not differ between responding tumors and non-responding tumors (6.58 ± 3.33 vs 4.74 ± 1.83, P = 0.078). An exploratory ROC curve analysis indicated that SUVmean [area under the ROC curve (AUC) = 0.700] was a better parameter than SUVpeak (AUC = 0.689) for predicting response. Using a threshold value of 3.82, high SUVmean at baseline was associated with improved PFS (5.0 vs. 3.4 months, log-rank P = 0.036). CONCLUSION: 18F-RGD uptake on PET/CT imaging pretreatment may predict the response to antiangiogenic therapy, with higher 18F-RGD uptake in tumors predicting a better response to apatinib therapy.

Impact of different respiratory gating methods on target delineation and a radiotherapy plan for solitary pulmonary tumors.

BACKGROUND AND PURPOSE: Respiratory movement has an important impact on the radiotherapy for lung tumor. Respiratory gating technology is helpful to improve the accuracy of target delineation. This study investigated the value of prospective and retrospective respiratory gating simulations in target delineation and radiotherapy plan design for solitary pulmonary tumors (SPTs) in radiotherapy. METHODS: The enrolled patients underwent CT simulation with three-dimensional (3D) CT non gating, prospective respiratory gating, and retrospective respiratory gating simulation. The target volumes were delineated on three sets of CT images, and radiotherapy plans were prepared accordingly. Tumor displacements and movement information obtained using the two respiratory gating approaches, as well as the target volumes and dosimetry parameters in the radiotherapy plan were compared. RESULTS: No significant difference was observed in tumor displacement measured using the two gating methods (p > 0.05). However, the internal gross tumor volumes (IGTVs), internal target volumes (ITVs), and planning target volumes (PTVs) based on the retrospective respiratory gating simulation were larger than those obtained using prospective gating (group A: pIGTV = 0.041, pITV = 0.003, pPTV = 0.008; group B: pIGTV = 0.025, pITV = 0.039, pPTV = 0.004). The two-gating PTVs were both smaller than those delineated on 3D non gating images (p < 0.001). V5Gy, V10Gy, V20Gy, V30Gy, and mean lung dose in the two gated radiotherapy plans were lower than those in the 3D non gating plan (p < 0.001); however, no significant difference was observed between the two gating plans (p > 0.05). CONCLUSIONS: The application of respiratory gating could reduce the target volume and the radiation dose that the normal lung tissue received. Compared to prospective respiratory gating, the retrospective gating provides more information about tumor movement in PTV.

Target volumes comparison between postoperative simulation magnetic resonance imaging and preoperative diagnostic magnetic resonance imaging for prone breast radiotherapy after breast-conserving surgery.

BACKGROUND: This study investigated the differences in target volumes between preoperative magnetic resonance imaging (MRIpre) and postoperative MRI (MRIpost) for breast radiotherapy after breast-conserving surgery (BCS) using deformable image registration (DIR). METHODS AND MATERIALS: Seventeen eligible patients who underwent whole-breast irradiation in the prone position after BCS were enrolled. On MRIpre, the gross tumor volume (GTV) was delineated as GTVpre, which was then expanded by 10 mm to represent the preoperative lumpectomy cavity (LC), denoted as LCpre. The LC was expanded to the clinical target volume (CTV) and planning target volume (PTV) on the MRIpre and MRIpost, denoted as CTVpre, CTVpost, PTVpre, and PTVpost, respectively. The MIM software system was used to register the MRIpre and MRIpost using DIR. Differences were evaluated regarding target volume, distance between the centers of mass (dCOM), conformity index (CI), and degree of inclusion (DI). The relationship between CILC /CIPTV and the clinical factors was also assessed. RESULTS: Significant differences were observed in LC and PTV volumes between MRIpre and MRIpost (p < 0.0001). LCpre was 0.85 cm3 larger than LCpost, while PTVpre was 29.38 cm3 smaller than PTVpost. The dCOM between LCpre and LCpost was 1.371 cm, while that between PTVpre and PTVpost reduced to 1.348 cm. There were statistically significant increases in CI and DI for LCpost-LCpre and PTVpost-PTVpre (CI = 0.221, 0.470; DI = 0.472, 0.635). No obvious linear correlations (p > 0.05) were found between CI and GTV, primary tumor volume-to-breast volume ratio, distance from the primary tumor to the nipple and chest wall, and body mass index. CONCLUSIONS: Despite using DIR technology, the spatial correspondence of target volumes between MRIpre and MRIpost was suboptimal. Therefore, relying solely on preoperative diagnostic MRI with DIR for postoperative LC delineation is not recommended.

Analysis of the advantage of individual PTVs defined on axial 3D CT and 4D CT images for liver cancer.

The purpose of this study was to compare positional and volumetric differences of planning target volumes (PTVs) defined on axial three dimensional CT (3D CT) and four dimensional CT (4D CT) for liver cancer. Fourteen patients with liver cancer underwent 3D CT and 4D CT simulation scans during free breathing. The tumor motion was measured by 4D CT. Three internal target volumes (ITVs) were produced based on the clinical target volume from 3DCT (CTV3D): i) A conventional ITV (ITVconv) was produced by adding 10 mm in CC direction and 5 mm in LR and and AP directions to CTV3D; ii) A specific ITV (ITVspec) was created using a specific margin in transaxial direction; iii) ITVvector was produced by adding an isotropic margin derived from the individual tumor motion vector. ITV4D was defined on the fusion of CTVs on all phases of 4D CT. PTVs were generated by adding a 5 mm setup margin to ITVs. The average centroid shifts between PTVs derived from 3DCT and PTV4D in left-right (LR), anterior-posterior (AP), and cranial-caudal (CC) directions were close to zero. Comparing PTV4D to PTVconv, PTVspec, and PTVvector resulted in a decrease in volume size by 33.18% ± 12.39%, 24.95% ± 13.01%, 48.08% ± 15.32%, respectively. The mean degree of inclusions (DI) of PTV4D in PTVconv, and PTV4D in PTVspec, and PTV4D in PTVvector was 0.98, 0.97, and 0.99, which showed no significant correlation to tumor motion vector (r = -0.470, 0.259, and 0.244; p = 0.090, 0.371, and 0.401). The mean DIs of PTVconv in PTV4D, PTVspec in PTV4D, and PTVvector in PTV4D was 0.66, 0.73, and 0.52. The size of individual PTV from 4D CT is significantly less than that of PTVs from 3DCT. The position of targets derived from axial 3DCT images scatters around the center of 4D targets randomly. Compared to conventional PTV, the use of 3D CT-based PTVs with individual margins cannot significantly reduce normal tissues being unnecessarily irradiated, but may contribute to reducing the risk of missing targets for tumors with large motion.

[Comparison of three methods to delineate internal gross target volume of the primary hepatocarcinoma based on four-dimensional CT simulation images].

OBJECTIVE: To compare the position and magnitude of internal target gross volume (IGTV) of primary hepatocarcinoma delineated by three methods based on four-dimensional computed tomography (4D-CT) and to investigate the relevant factors affecting the position and magnitude. METHODS: Twenty patients with primary hepatocarcinoma after transcatheter arterial chemoembolization (TACE) underwent big bore 4D-CT simulation scan of the thorax and abdomen using a real-time position management (RPM) system for simultaneous record of the respiratory signals. The CT images with respiratory signal data were reconstructed and sorted into 10 phase groups in a respiratory cycle, with 0% phase corresponding to end-inhale and 50% corresponding to end-exhale. The maximum intensity projection (MIP) image was generated. IGTVs of the tumor were delineated using the following three methods: (1) The gross tumor volume (GTV) on each of the ten respiratory phases of the 4D-CT image set was delineated and fused ten GTV to produce IGTV10; (2) The GTVs delineated separately based on 0% and 50% phase were fused to produce IGTV(IN+EX); (3) The visible tumor on the MIP image was delineated to produce IGTV(MIP). Twenty patients were divided into groups A and B based on the location of the target center,and were divided into groups C and D based on the tumor maximum diameter. The patients were divided into groups E and F based on the three-dimensional (3D) motion vector of the target center. The position of the target center, the volume of target, the degree of inclusion (DI) and the matching index (MI) were compared reciprocally between IGTV10, IGTV(IN+EX) and IGTV(MIP), and the influence of the tumor position and 3D motion vector on the related parameters were compared based on the grouping. RESULTS: The average differences between the position of the center of IGTVs on direction of X, Y and Z axes were less than 1.5 mm, and the difference was statistically not significant. The volume of IGTV10 was larger than that of IGTV(IN+EX), but the difference was not significant (t = 0.354, P = 0.725). The volume of IGTV10 was larger than that of IGTV(MIP) but the difference was not significant (t = -0.392, P = 0.697). The ratio of IGTV(IN+EX) to IGTV10 was 0.75 +/- 0.15 and the ratio of IGTV(MIP) to IGTV10 was 0.78 +/- 0.14. The DI of IGTV(IN+EX) in IGTV10 was (74.85 +/- 15.09)% and that of IGTV(MIP) in IGTV10 was (68.87 +/- 13.69)%. The MI between IGTV10 and IGTV(IN+EX), IGTV10 and IGTV(MIP) were 0.75 +/- 0.15 and 0.67 +/- 0.13, respectively. The median of ratio of IGTV(IN+EX)/ IGTV10 was 0.57 in group A versus 0.87 in group B, statistically with a significant difference between the groups A and B (Z = -3.300,P = 0.001). The median of ratio of IGTV(MIP)/IGTV10 was 0.51 in the group A and 0.72 in group B, with a significant difference between the groups A and B (Z = -3.413, P = 0.001). The median of ratio of IGTV(IN+EX)/IGTV10 was 0.79 in group C versus 0.74 in group D, with a difference not significant (Z = -0.920, P = 0.358). The median of ratio of IGTV(MIP)/IGTV10 was 0.85 in group C versus 0.80 in group D, with a non-significant difference (Z = -0.568, P = 0.570). The median of ratio of IGTV(IN+EX)/IGTV10 was 0.87 in group E versus 0.68 in group F, with a significant difference between the two groups (Z = -2.897, P = 0.004). The median of ratio of IGTV(MIP)/IGTV10 was 0.85 in the group E versus 0.81 in the group F, with a non-significant difference (Z = -0.568, P = 0.570). CONCLUSIONS: The center displacement of the IGTVs delineated separately by the three techniques based on 4D-CT images is not obvious. IGTV(IN+EX) and IGTV(MIP) can not replace IGTV10, however, IGTV(IN+EX) is more close to IGTV10 comparing with IGTV(MIP). The ratio of IGTV10 and IGTV(MIP) is correlated to the 3D motion vector of the tumor. When the tumor is situated in the upper part of the liver and with a 3D motion vector less than 9 mm, IGTV10 should be the best IGTV.

[Displacement of the silver clips in surgical cavity based on four-dimensional CT images for patients undertaking external-beam partial breast irradiation after breast-conserving surgery].

OBJECTIVE: To explore the displacement of the selected clips and the center of the geometry consisted of all the clips in the surgical cavity measured on the basis of four-dimensional computed tomography (4D-CT) simulation images. METHODS: Fourteen breast cancer patients after breast-conserving surgery were recruited for external beam partial-breast irradiation (EB-PBI), and received large aperture CT simulation. The 4D-CT image data sets were collected when the patient was in the free breathing state. Using the Varian Eclipse treatment planning system, the selected four clips in the cavity were separately delineated on the CT images from 10 phases of the breath cycle, and all of the clips in the cavity were marked to obtain the geometry. Then the displacement of the four selected clips and the center of the geometry in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were measured. The differences of the displacement were compared. RESULTS: The displacements in the AP and SI directions were always greater than the displacement in LR direction for the same selected clip. The difference of the displacements in the same direction of the different selected clips was not statistically significant (P>0.05). The displacements of the geometry center consisted of all of the clips in the LR, AP, SI directions were (1.34±0.39) mm, (2.01±1.02) mm and (1.89±1.03) mm, respectively, and the difference of the displacements between LR and AP, LR and SI were all statistically significant (P<0.05). In the same directions (LR, AP and SI), the displacement of geometry center was always greater than the displacement of the selected clips, and the difference except SI direction was all statistically significant (P<0.05). In the SI direction, the association between the displacement of geometry center and the upper clip, geometry center and the lower clip was statistically significant (P<0.05). CONCLUSION: When the target for EB-PBI is defined on the basis of 4D-CT simulation images, the displacement of the selected clips at the border of the surgical cavity is not qualified to substitute the displacement of the target defined basing on all of the clips in the surgical cavity.

Reproducibility for Hepatocellular Carcinoma CT Radiomic Features: Influence of Delineation Variability Based on 3D-CT, 4D-CT and Multiple-Parameter MR Images.

Purpose: Accurate lesion segmentation is a prerequisite for radiomic feature extraction. It helps to reduce the features variability so as to improve the reporting quality of radiomics study. In this research, we aimed to conduct a radiomic feature reproducibility test of inter-/intra-observer delineation variability in hepatocellular carcinoma using 3D-CT images, 4D-CT images and multiple-parameter MR images. Materials and Methods: For this retrospective study, 19 HCC patients undergoing 3D-CT, 4D-CT and multiple-parameter MR scans were included in this study. The gross tumor volume (GTV) was independently delineated twice by two observers based on contrast-enhanced computed tomography (CECT), maximum intensity projection (MIP), LAVA-Flex, T2W FRFSE and DWI-EPI images. We also delineated the peritumoral region, which was defined as 0 to 5 mm radius surrounding the GTV. 107 radiomic features were automatically extracted from CECT images using 3D-Slicer software. Quartile coefficient of dispersion (QCD) and intraclass correlation coefficient (ICC) were applied to assess the variability of each radiomic feature. QCD<10% and ICC≥0.75 were considered small variations and excellent reliability. Finally, the principal component analysis (PCA) was used to test the feasibility of dimensionality reduction. Results: For tumor tissues, the numbers of radiomic features with QCD<10% indicated no obvious inter-/intra-observer differences or discrepancies in 3D-CT, 4D-CT and multiple-parameter MR delineation. However, the number of radiomic features (mean 89) with ICC≥0.75 was the highest in the multiple-parameter MR group, followed by the 3DCT group (mean 77) and the MIP group (mean 73). The peritumor tissues also showed similar results. A total of 15 and 7 radiomic features presented excellent reproducibility and small variation in tumor and peritumoral tissues, respectively. Two robust features showed excellent reproducibility and small variation in tumor and peritumoral tissues. In addition, the values of the two features both represented statistically significant differences among tumor and peritumoral tissues (P<0.05). The PCA results indicated that the first seven principal components could preserve at least 90% of the variance of the original set of features. Conclusion: Delineation on multiple-parameter MR images could help to improve the reproducibility of the HCC CT radiomic features and weaken the inter-/intra-observer influence.

The Predictive Value of Tumor Volume and Its Change on Short-Term Outcome for Esophageal Squamous Cell Carcinoma Treated With Radiotherapy or Chemoradiotherapy.

OBJECTIVES: To investigate the tumor volume and its change on short-term outcome in esophageal squamous cell carcinoma (ESCC) patients who underwent definitive radiotherapy or chemoradiotherapy. METHODS AND MATERIALS: All data were retrospectively collected from 418 ESCC patients who received radiotherapy or chemoradiotherapy at our institution between 2015 and 2019. Short-term outcome using the treatment response evaluation was assessed according to the RECIST 1.1. The tumor volume change rate (TVCR) was defined as follows: TVCR = {1 - [gross tumor volume (GTV) at shrinking irradiation field planning)]/(GTV at the initial treatment planning)} ×100%. Chi square test was used to compare the clinic characteristics in different TVCR groups, and the difference between initial GTV (GTVi) and shrinking GTV (GTVs) was compared using Wilcoxon's sign rank test. Logistic regression analysis and Spearman correlation was performed. RESULTS: There was a significant decrease in GTVi compared to GTVs (P < 0.001). In univariate analysis, age, cT-stage, TNM stage, treatment modality, GTVi, and TVCR were associated with short-term outcome (all P < 0.05). In multivariate analysis, gender and TVCR were statistically significant (P = 0.010, <0.001) with short-term outcome, and the combined predictive value of gender and TVCR exceeded that of TVCR (AUC, 0.876 vs 0.855). CONCLUSIONS: TVCR could serve to forecast short-term outcome of radiotherapy or chemoradiotherapy in ESCC. It was of great significance to guide the individualized treatment of ESCC.

Geometric accuracy evaluation of a six-degree-of-freedom (6-DoF) couch with cone beam computed tomography (CBCT) using a phantom and correlation study of the position errors in pelvic tumor radiotherapy.

BACKGROUND: To assess the position accuracy of the six-degree-of-freedom (6-DoF) couch based on cone beam computed tomography (CBCT) and exploit the correlation of the six degrees errors. METHODS: CT scans of an anthropomorphic phantom and patients were obtained at 3 mm slice thicknesses using a Philips scanner at the head, first supine and prostrate positions. An Eclipse Treatment Planning System was used to create a treatment plan. Different levels of known position errors were introduced to simulate patient position status for the anthropomorphic phantom. CBCT datasets for each position were acquired and registered to original CT datasets to evaluate the accuracy of the 6-DoF couch and determine the setup errors of patients. The setup errors of 200 CBCT datasets from 14 patients with pelvic tumors were analyzed. The correlations between six degrees position errors were finally extracted. RESULTS: For the phantom study, the difference between known introduced errors and the setup errors were almost negligible. The deviation (mean ± one standard deviation) in registration methods were (0.01±0.02) cm, (0.04±0.075) cm, (0.02±0.004) cm, (0.01±0.04)°, (0.1±0.08)°, (0.03±0.05)° and (0.01±0.01) cm, (0.03±0.007) cm, (0.01±0.01) cm, (0.05±0.06)°, (0.08±0.08)°, (0.04±0.05)° for supine and prone position, respectively. The deviation in positions were (0.07±0.10) cm, (0.16±0.02) cm, (0.08±0.06) cm, (0.54±0.46)°, (0.24±0.16)°, (0.09±0.09)° and (0.06±0.09) cm, (0.19±0.09) cm, (0.09±0.07) cm, (0.49±0.49)°, (0.16±0.08)°, (0.1±0.13)° for bone and soft tissue registration methods, respectively. For patient data, the setup errors were (-0.07±0.22) cm, (0.14±0.35) cm, (-0.12±0.4) cm, (0.79±1.6)°, (0.41±0.71)°, (-0.03±0.8)° for supine position and (0.16±0.27) cm, (0.19±0.48) cm, (-0.05±0.34) cm, (1.1±1.49)°, (0.65±1.00)°, (-0.23±0.75)° for prone position, respectively. There is a significant moderate correlation between the longitudinal and pitch directions and between the vertical and pitch directions when the patient is in the supine position. CONCLUSIONS: The six-dimensional couch positioning verification system based on CBCT has high accuracy and can meet the requirements of precise radiotherapy for pelvic tumors. There is a certain correlation between translation direction and rotation direction.

The flow-metabolism ratio might predict treatment response and survival in patients with locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Perfusion CT can offer functional information about tumor angiogenesis, and 18F-FDG PET/CT quantifies the glucose metabolic activity of tumors. This prospective study aims to investigate the value of biologically relevant imaging biomarkers for predicting treatment response and survival outcomes in patients with locally advanced esophageal squamous cell cancer (LA ESCC). METHODS: Twenty-seven patients with pathologically proven ESCC were included. All patients had undergone perfusion CT and 18F-FDG PET/CT using separate imaging systems before receiving definitive chemoradiotherapy (dCRT). The perfusion parameters included blood flow (BF), blood volume (BV), and time to peak (TTP), and the metabolic parameters included maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The flow-metabolism ratio (FMR) was defined as BF divided by SUVmax. Statistical methods used included Spearman's rank correlation, Mann-Whitney U test or two-sample t test, receiver operating characteristic (ROC) curve analysis, the Kaplan-Meier method, and Cox proportional hazards models. RESULTS: The median overall survival (OS) and progression-free survival (PFS) were 18 and 11.6 months, respectively. FMR was significantly positively correlated with BF (r = 0.886, p < 0.001) and negatively correlated with SUVmax (r = - 0.547, p = 0.003) and TTP (r = - 0.462, p = 0.015) in the tumors. However, there was no significant correlation between perfusion and PET parameters. After dCRT, 14 patients (51.9%) were identified as responders, and another 13 were nonresponders. The BF and FMR of the responders were significantly higher than those of the nonresponders (42.05 ± 16.47 vs 27.48 ± 8.55, p = 0.007; 3.18 ± 1.15 vs 1.84 ± 0.65, p = 0.001). The ROC curves indicated that the FMR [area under the curve (AUC) = 0.846] was a better biomarker for predicting treatment response than BF (AUC = 0.802). Univariable Cox analysis revealed that of all imaging parameters, only the FMR was significantly correlated with overall survival (OS) (p = 0.015) and progression-free survival (PFS) (p = 0.017). Specifically, patients with a lower FMR had poorer survival. Multivariable analysis showed that after adjusting for age, clinical staging, and treatment response, the FMR remained an independent predictor of OS (p = 0.026) and PFS (p = 0.014). CONCLUSIONS: The flow-metabolism mismatch demonstrated by a low FMR shows good potential in predicting chemoradiotherapy sensitivity and prognosis in ESCC.

Incidence and prognosis of brain metastases in cutaneous melanoma patients: a population-based study.

Brain metastases (BM) from cutaneous melanoma are associated with poor prognosis. Population-based data describing the associated factors of incidence and prognosis of BM from melanoma are still lacking. We identified 121 255 melanoma patients diagnosed during 2010-2015 from the Surveillance, Epidemiology, and End Results program, and identified predictive factors for incidence and survival of BM patients by using multivariable logistic and Cox's proportional hazard regression, respectively. We identified 1547 patients with BM at the time of diagnosis of malignant cutaneous melanoma, representing 1.3% of the entire cohort and 35.4% of the subset with metastatic disease. The characteristics associated with higher BM incidence were male sex, age 40-60 years, melanoma location of face/head/neck, histologic type of nodular, higher T-stage, ulceration and extracranial metastases. The median overall survival and median cutaneous melanoma specific survival of patients with BM was 5 and 6 months, respectively. The relative factors of poor survival were older age and more extracranial metastatic sites. In summary, we provided insight into the epidemiology of BM from cutaneous melanoma. These results may provide significant help to improve the screening strategy of BM strategy and update the existing prognosis evaluation system.

18F-Fluorodeoxyglucose positron emission tomography may not visualize radiation pneumonitis.

BACKGROUND: Radiation pneumonitis is a common and potentially fatal complication of radiotherapy (RT). Some patients with radiation pneumonitis show increases in uptake of fluorodeoxyglucose (FDG) on positron emission tomography (PET), but others do not. The exact relationship between radiation pneumonitis and 18F-FDG PET findings remains controversial. METHODS: We used an animal model of radiation pneumonitis involving both radiation and simulated bacterial infection in Wistar rats. Treatment groups (10 rats/group) were as follows: control, RT-only, lipopolysaccharide (LPS)-only, and RT+LPS. All rats had micro-PET scans at 7 weeks after RT (or sham). Histologic, immunohistochemical, and biochemical analyses were performed to evaluate potential mechanisms. RESULTS: Irradiated rats had developed radiation pneumonitis at 7 weeks after RT based on pathology and CT scans. Maximum and mean standardized uptake values (SUVmax and SUVmean) at that time were significantly increased in the LPS group (P < 0.001 for both) and the RT+LPS group (P < 0.001 for both) relative to control, but were not different in the RT-only group (P = 0.156 SUVmax and P = 0.304 SUVmean). The combination of RT and LPS increased the expression of the aerobic glycolysis enzyme PKM2 (P < 0.001) and the glucose transporter GLUT1 (P = 0.004) in lung tissues. LPS alone increased the expression of PKM2 (P = 0.018), but RT alone did not affect PKM2 (P = 0.270) or GLUT1 (P = 0.989). CONCLUSIONS: Aseptic radiation pneumonitis could not be accurately assessed by 18F-FDG PET, but was visualized after simulated bacterial infection via LPS. The underlying mechanism of the model of bacterial infection causing increased FDG uptake may be the Warburg effect.

Effects of respiratory motion on volumetric and positional difference of GTV in lung cancer based on 3DCT and 4DCT scanning.

Differences in gross target volume (GTV) and central point positions among moving lung cancer models constructed by CT scanning at different frequencies were compared, in order to explore the effect of different respiratory frequencies on the GTV constructions in moving lung tumors. Eight models in different shapes and sizes were established to stimulate lung tumors. The three-dimensional computed tomography (3DCT) and four-dimensional computed tomography (4DCT) scanning were performed at 10, 15 and 20 times/min in different models. Differences in GTV volumes and central point positions at different motion frequencies were compared by means of GTV3Ds (GTV3D-10, GTV3D-15, GTV3D-20) and IGTV4Ds (IGTV4D-10, IGTV4D-15, IGTV4D-20). Volumes of GTV3D-10, GTV3D-15, GTV3D-20 were 12.41±14.26, 10.38±11.18 and 12.50±15.23 cm3 respectively (P=0.687). Central point coordinates in the x-axis direction were -8.16±96.21, -8.57±96.08 and -8.56±95.73 respectively (P=0.968). Central point coordinates in the y-axis direction were 108.22±25.03, 110.41±22.47 and 109.04±24.24 (P=0.028). Central point coordinates in the z-axis direction were 65.19±13.68, 65.43±13.40 and 65.38±13.17 (P=0.902). The difference was significant in the y-axis direction (P=0.028). Volumes of IGTV4D-10, IGTV4D-15, IGTV4D-20 were 17.78±19.42, 17.43±19.56 and 17.44±18.80 cm3 (P=0.417). Central point coordinates in the x-axis direction were -7.73±95.93, -7.86±95.56 and -7.92±95.14 (P=0.325). Central point coordinates in the y-axis direction were 109.41±24.54, 109.60±24.13 and 109.16±24.28 (P=0.525). Central point coordinates in the z-axis direction were 65.52±13.31, 65.59±13.39 and 65.51±13.34 (P=0.093). However, the central point position of GTV in the head and foot direction by 3DCT scanning was severely affected by the respiratory frequency.

Dosimetric evaluation of four whole brain radiation therapy approaches with hippocampus and inner ear avoidance and simultaneous integrated boost for limited brain metastases.

AIMS: To perform a dosimetric evaluation of four different simultaneous integrated boost whole brain radiotherapy modalities with hippocampus and inner ear avoidance in the treatment of limited brain metastases. METHODS: Computed tomography/magnetic resonance imaging data of 10 patients with limited (1-5) brain metastases were used to replan step-and-shoot intensity-modulated radiotherapy (sIMRT), dynamic intensity-modulated radiation therapy (dIMRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (Tomo). The prescribed doses of 40-50 Gy in 10 fractions and 30 Gy in 10 fractions were simultaneously delivered to the metastatic lesions and the whole-brain volume, respectively. The hippocampal dose met the RTOG 0933 criteria for hippocampal avoidance (Dmax ≤17 Gy, D100% ≤10 Gy). The inner ear dose was restrained to Dmean ≤15 Gy. Target coverage (TC), homogeneity index (HI), conformity index (CI), maximum dose (Dmax), minimum dose (Dmin) and dose to organs at risk (OARs) were compared. RESULTS: All plans met the indicated dose restrictions. The mean percentage of planning target volume of metastases (PTVmets) coverage ranged from 97.1 to 99.4%. For planning target volume of brain (PTVbrain), Tomo provided the lowest average D2% (37.5 ± 2.8 Gy), the highest average D98% (25.2 ± 2.0 Gy), and the best TC (92.6% ± 2.1%) and CI (0.79 ± 0.06). The two fixed gantry IMRT modalities (step and shot, dynamic) provided similar PTVbrain dose homogeneity (both 0.76). Significant differences across the four approaches were observed for the maximum and minimum doses to the hippocampus and the maximum doses to the eyes, lens and optic nerves. CONCLUSION: All four radiotherapy modalities produced acceptable treatment plans with good avoidance of the hippocampus and inner ear. Tomo obtained satisfactory PTVbrain coverage and the best homogeneity index. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03414944 . Registered 29 January 2018.

Dosimetric and Radiobiological Comparison of External Beam Radiotherapy Using Simultaneous Integrated Boost Technique for Esophageal Cancer in Different Location.

Objectives: To compare treatment plans of intensity modulated radiotherapy (IMRT), volumetric modulated arc radiotherapy (VMAT), and helical tomotherapy (HT) with simultaneous integrated boost (SIB) technique for esophageal cancer (EC) of different locations using dosimetry and radiobiology. Methods: Forty EC patients were planned for IMRT, VMAT, and HT plans, including 10 cases located in the cervix, upper, middle, and lower thorax, respectively. Dose-volume metrics, conformity index (CI), homogeneity index (HI), tumor control probability (TCP), and normal tissue complication probability (NTCP) were analyzed to evaluate treatment plans. Results: HT showed significant improvement over IMRT and VMAT in terms of CI (p = 0.007), HI (p < 0.001), and TCP (p < 0.001) in cervical EC. IMRT yielded more superior CI, HI and TCP compared with VMAT and HT in upper and middle thoracic EC (all p < 0.05). Additionally, V30 (27.72 ± 8.67%), mean dose (1801.47 ± 989.58cGy), and NTCP (Niemierko model: 0.44 ± 0.55%; Lyman-Kutcher-Burman model: 0.61 ± 0.59%) of heart in IMRT were sharply reduced than VMAT and HT in middle thoracic EC. For lower thoracic EC, the three techniques offered similar CI and HI (all p > 0.05). But VMAT dramatically lowered liver V30 (9.97 ± 2.84%), and reduced NTCP of lungs (Niemierko model: 0.47 ± 0.48%; Lyman-Kutcher-Burman model: 1.41 ± 1.07%) and liver (Niemierko model: 0.10 ± 0.08%; Lyman-Kutcher-Burman model: 0.17 ± 0.17%). Conclusions: HT was a good option for cervical EC with complex target coverage but little lungs and heart involvement as it achieved superior dose conformity and uniformity. Due to potentially improving tumor control and reducing heart dose with acceptable lungs sparing, IMRT was a preferred choice for upper and middle thoracic EC with large lungs involvement. VMAT could ameliorate therapeutic ratio and lower lungs and liver toxicity, which was beneficial for lower thoracic EC with little thoracic involvement but being closer to heart and liver. Individually choosing optimal technique for EC in different location will be warranted.

Comparison of different width detector on the gross tumor volume delineation of the solitary pulmonary lesion.

PURPOSE: To explore the impact of different width detector on the volume and geometric position of gross tumor volume (GTV) of the solitary pulmonary lesion (SPL), as well as the impact on scanning time and radiation dose during the simulation. MATERIALS AND METHODS: Twenty-three patients with SPL underwent three-dimensional computed tomography (3DCT) simulation using different width detector, followed by four-dimensional computed tomography (4DCT) scans. GTV16 and GTV4 derived from different width detectors were compared with internal gross tumor volume (IGTV) generated from 4DCT on the volume and geometric position. Fourteen patients with lesions located in the upper lobe were defined as Group A and nine patients in the middle or lower lobe were defined as Group B. The scanning time and radiation dose during the simulation with the different width detector were compared as well. RESULTS: The volumes of IGTV, GTV16, and GTV4 in Group A were 13.86 ± 14.42 cm3, 11.88 ± 11.93 cm3, and 11.64 ± 12.88 cm3, respectively, and the corresponding volumes in Group B were 12.84 ± 11.48 cm3, 6.90 ± 6.63 cm3, and 7.22 ± 7.15 cm3, respectively. No difference was found between GTV16 and GTV4 in Groups A and B (PA = 0.11, PB = 0.86). Either GTV16 or GTV4 was smaller than IGTV (P16 = 0.001, P4 = 0.000). The comparison of the centroidal positions in x, y, and z directions for GTV16, GTV4, and IGTV showed no significant difference both in Groups A and B (Group A: Px = 0.19, Py = 0.14, Pz = 0.47. Group B: Px = 0.09, Py = 0.90, Pz = 0.90). The scanning time was shorter and radiation dose patient received was lower using 16 × 1.5 mm detector combination than 4 × 1.5 mm detector (P = 0.000). CONCLUSIONS: Different width detector had no impact on the volume and geometric position of GTV of SPL during 3DCT simulation. Using wide detector would save time and decrease radiation dose compared with the narrow one. 3DCT simulation using either 16 × 1.5 mm detector or 4 × 1.5 mm detector could not cover all tumor motion information that 4DCT offered under free breathing conditions.

Comparison of internal target volumes defined on 3-dimensional, 4-dimensonal, and cone-beam CT images of non-small-cell lung cancer.

PURPOSE: The purpose of this study was to compare the positional and volumetric differences of internal target volumes defined on three-dimensional computed tomography (3DCT), four-dimensional CT (4DCT), and cone-beam CT (CBCT) images of non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Thirty-one patients with NSCLC sequentially underwent 3DCT and 4DCT simulation scans of the thorax during free breathing. The first CBCT was performed and registered to the planning CT using the bony anatomy registration during radiotherapy. The gross tumor volumes were contoured on the basis of 3DCT, maximum intensity projection (MIP) of 4DCT, and CBCT. CTV3D (clinical target volume), internal target volumes, ITVMIP and ITVCBCT, were defined with a 7 mm margin accounting for microscopic disease. ITV10 mm and ITV5 mm were defined on the basis of CTV3D: ITV10 mm with a 5 mm margin in left-right (LR), anterior-posterior (AP) directions and 10 mm in cranial-caudal (CC) direction; ITV5 mm with an isotropic internal margin (IM) of 5 mm. The differences in the position, size, Dice's similarity coefficient (DSC) and inclusion relation of different volumes were evaluated. RESULTS: The median size ratios of ITV10 mm, ITV5 mm, and ITVMIP to ITVCBCT were 2.33, 1.88, and 1.03, respectively, for tumors in the upper lobe and 2.13, 1.76, and 1.1, respectively, for tumors in the middle-lower lobe. The median DSCs of ITV10 mm, ITV5 mm, ITVMIP, and ITVCBCT were 0.6, 0.66, and 0.83 for all patients. The median percentages of ITVCBCT not included in ITV10 mm, ITV5 mm, and ITVMIP were 0.1%, 1.63%, and 15.21%, respectively, while the median percentages of ITV10 mm, ITV5 mm, and ITVMIP not included in ITVCBCT were 57.08%, 48.89%, and 20.04%, respectively. CONCLUSION: The use of the individual ITV derived from 4DCT merely based on bony registration in radiotherapy may result in a target miss. The ITVs derived from 3DCT with isotropic margins have a good coverage of the ITV from CBCT, but the use of those would result in a high proportion of normal tissue being irradiated unnecessarily.

Correlation of primary middle and distal esophageal cancers motion with surrounding tissues using four-dimensional computed tomography.

PURPOSE: To investigate the correlation of gross tumor volume (GTV) motion with the structure of interest (SOI) motion and volume variation for middle and distal esophageal cancers using four-dimensional computed tomography (4DCT). PATIENTS AND METHODS: Thirty-three patients with middle or distal esophageal carcinoma underwent 4DCT simulation scan during free breathing. All image sets were registered with 0% phase, and the GTV, apex of diaphragm, lung, and heart were delineated on each phase of the 4DCT data. The position of GTV and SOI was identified in all 4DCT phases, and the volume of lung and heart was also achieved. The phase relationship between the GTV and SOI was estimated through Pearson's correlation test. RESULTS: The mean peak-to-peak displacement of all primary tumors in the lateral (LR), anteroposterior (AP), and superoinferior (SI) directions was 0.13 cm, 0.20 cm, and 0.30 cm, respectively. The SI peak-to-peak motion of the GTV was defined as the greatest magnitude of motion. The displacement of GTV correlated well with heart in three dimensions and significantly associated with bilateral lung in LR and SI directions. A significant correlation was found between the GTV and apex of the diaphragm in SI direction (r left=0.918 and r right=0.928). A significant inverse correlation was found between GTV motion and varying lung volume, but the correlation was not significant with heart (r LR=-0.530, r AP=-0.531, and r SI=-0.588) during respiratory cycle. CONCLUSION: For middle and distal esophageal cancers, GTV should expand asymmetric internal margins. The primary tumor motion has quite good correlation with diaphragm, heart, and lung.

Perfusion computed tomography in predicting treatment response of advanced esophageal squamous cell carcinomas.

BACKGROUND: The purpose of this study was to prospectively evaluate the predictive value of perfusion computed tomography (CT) for response of local advanced esophageal carcinoma to radiotherapy and chemotherapy. MATERIALS AND METHODS: Before any treatment, forty-three local advanced esophageal squamous cell carcinomas were prospectively evaluated by perfusion scan with 16-row CT from June 2009 to January 2012. Perfusion parameters, including perfusion (BF), peak enhanced density (PED), blood volume (BV), and time to peak (TTP) were measured using Philips perfusion software. Seventeen cases received definitive radiotherapy and 26 received concurrent chemo-radiotherapy. The response was evaluated by CT scan and esophagography. Differences in perfusion parameters between responders and non-responders were analyzed, and ROCs were used to assess predictive value of the baseline parameters for treatment response. RESULTS: There were 25 responders (R) and 18 non-responders (NR). Responders showed significantly higher BF (R:34.1 ml/100 g/min vs NR: 25.0 ml/100 g/min, p=0.001), BV (23.2 ml/100g vs 18.3 ml/100g, p=0.009) and PED (32.5 HU vs 28.32 HU, P=0.003) than non-responders. But the baseline TTP (R: 38.2 s vs NR: 44.10 s, p=0.172) had no difference in the two groups. For baseline BF, a threshold of 36.1 ml/100 g/min achieved a sensitivity of 56%, and a specificity of 94.4% for detection of clinical responders from non-responders. CONCLUSIONS: The results suggest that the perfusion CT can provide some helpful information for identifying tumors that may respond to radio-chemotherapy.

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.