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In the delivery of stereotactic radiosurgery (SRS) by linear accelerator (LINAC), dynamic conformal arc therapy (DCAT) with non-coplanar beams is conventionally used. However, volumetric modulated arc therapy (VMAT) can improve target conformity, thereby decreasing the dose to organs at risk by inversed planning methods, but few studies have directly compared DCAT and VMAT with and without non-coplanar beams in patients with single brain metastasis. We therefore conducted a planning study to compare the dose distribution in DCAT, VMAT using only a coplanar arc (CoVMAT) and VMAT with non-coplanar arcs (NcVMAT) in the treatment of single brain metastasis. DCAT, CoVMAT and NcVMAT plans were created for 15 patients. The three modalities were compared in terms of target conformity, target coverage, the dose to normal brain tissue, monitor units (MUs) and beam-on time. Both conformity indices (RTOG-CI and IP-CI) as well as the D98% of the gross target volume (GTV) were significantly better in the NcVMAT plans than in the DCAT plans. Comparisons of the doses to normal brain tissue revealed that the V20Gy, V15Gy, V12Gy, V10Gy and V5Gy were significantly smaller in the NcVMAT plans than in the plans based on the other two modalities. The MUs of the DCAT and NcVMAT plans were larger than those of the CoVMAT plans, and the beam-on time was longer in the NcVMAT and CoVMAT plans than in the DCAT plans. Compared to the CoVMAT and DCAT plans, NcVMAT plans significantly improved target conformity and reduced the doses to normal brain tissue at V20Gy, V15Gy, V12Gy, V10Gy and V5Gy.

PURPOSE To investigate the clinical value of transrectal ultrasound in judging the Gross Target Volume (GTV) of cervical cancer (CC). METHODS A total of 196 CC patients admitted to the Department of Radiotherapy, China-Japan Union Hospital, Jilin University, from January 2016 to June 2019 were selected as the study subjects. The GTVs before and after applicator insertion were determined by transrectal ultrasound and compared with those judged by MRI. RESULTS All 196 patients were successfully undergoing applicator insertion according to the pretreatment plan. The GTV doses reached the clinical requirements during treatment. There was no significant difference between the GTVs judged by MRI and ultrasound before insertion in terms of upper/lower diameter (MRI Before 1 vs. Ultrasound Before 1) (MB1 vs. UB1), left/right diameter (MB2 vs. UB2), or ventral/dorsal diameter (MB3 vs. UB3), and the intragroup correlation coefficients (ICC) were 0.59, 0.77, and 0.66, respectively; moreover, there was no significant difference between the GTVs judged by MRI and ultrasound after insertion in terms of MRI After one vs. Ultrasound After one (MA1 vs. UA1), MA2 vs. UA2, and MA3 vs. UA3, and the ICC values were 0.62, 0.79, and 0.76, respectively. CONCLUSIONS Transrectal ultrasound can satisfactorily determine the GTV of CC and has certain value in brachytherapy for CC.

Shuli Hu,1 Man Luo,2 Yaling Li1 1Department of Intensive Care Unit, Wuhan No. 1 Hospital, Wuhan, 430022, People’s Republic of China; 2Department of Oncology, Wuhan No.1 Hospital, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Yaling LiDepartment of Intensive Care Unit, Wuhan No.1 Hospital, 215 Zhongshan Road, Wuhan, Hubei Province, People’s Republic of ChinaTel +86 027-85332691Email 2861696710@qq.comPurpose: The lymph node gross target volume (GTV) delineation in patients with non-small cell lung cancer (NSCLC) is crucial for prognosis. This study aimed to develop a predictive model that can be used to differentiate between lymph nodes micrometastasis (LNM) and non-lymph nodes micrometastasis (non-LNM).Patients and Methods: A retrospective study involving 1524 patients diagnosed with NSCLC was collected in the First Hospital of Wuhan between January 1, 2017, and April 1, 2020. Duplicated and useless variables were excluded, and 16 candidate variables were selected for further analysis. The random forest (RF) algorithm and generalized linear (GL) algorithm were used to screen out the variables that greatly affected the LNM prediction, respectively. The area under the curve (AUC) was compared between the RF model and GL model.Results: The RF model revealed that the variables, including pathology, degree of differentiation, maximum short diameter of lymph node, tumor diameter, pulmonary membrane invasion, clustered lymph nodes, and T stage, were more significant for LNM prediction. Multifactorial logistic regression analysis for the GL model indicated that vascular invasion, tumor diameter, degree of differentiation, pulmonary membrane invasion, and maximum standard uptake value (SUVmax) were positively associated with LNM. The AUC for the RF model and GL model was 0.83 (95% CI: 0.75 to 0.90) and 0.64 (95% CI: 0.60 to 0.70), respectively.Conclusion: We successfully established an accurate and optimized RF model that could be used to predict LNM in patients with NSCLC. This model can be used to evaluate the risk of an individual patient experiencing LNM and therefore facilitate the choice of treatment.Keywords: non-small cell lung cancer, lymph nodes micrometastasis, prediction model, random forest, gross target volume, machine learning

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.

PurposeTo simulate and analyze the dosimetric differences of intraoperative radiotherapy (IORT) or pre-operative single-fraction stereotactic radiosurgery (SRS) in addition to post-operative external beam radiotherapy (EBRT) in Glioblastoma (GB).MethodsImaging series of previously treated patients with adjuvant radiochemotherapy were analyzed. For SRS target definition, pre-operative MRIs were co-registered to planning CT scans and a pre-operative T1-weighted gross target volume (GTV) plus a 2-mm planning target volume (PTV) were created. For IORT, a modified (m)GTV was expanded from the pre-operative volume, in order to mimic a round cavity as during IORT. Dose prescription was 20 Gy, homogeneously planned for SRS and calculated at the surface for IORT, to cover 99% and 90% of the volumes, respectively. For tumors > 2cm in maximum diameter, a 15 Gy dose was prescribed. Plan assessment was performed after calculating the 2-Gy equivalent doses (EQD2) for both boost modalities and including them into the EBRT plan. Main points of interest encompass differences in target coverage, brain volume receiving 12 Gy or more (V12), and doses to various organs-at-risk (OARs).ResultsSeventeen pre-delivered treatment plans were included in the study. The mean GTV was 21.72 cm3 (SD ± 19.36) and mGTV 29.64 cm3 (SD ± 25.64). The mean EBRT and SRS PTV were 254.09 (SD ± 80.0) and 36.20 cm3 (SD ± 31.48), respectively. Eight SRS plans were calculated to 15 Gy according to larger tumor sizes, while all IORT plans to 20 Gy. The mean EBRT D95 was 97.13% (SD ± 3.48) the SRS D99 99.91% (SD ± 0.35) and IORT D90 83.59% (SD ± 3.55). Accounting for only-boost approaches, the brain V12 was 49.68 cm3 (SD ± 26.70) and 16.94 cm3 (SD ± 13.33) (pmax of chiasma (p=0.01), left optic nerve (p=0.023), right (p=0.008) and left retina (pConclusionDose escalation for Glioblastoma using IORT results in lower OAR exposure as conventional SRS.

Purpose: The purpose of this study was to investigate the overlaps between gross target volume (GTV) and the celiac artery (CA) and superior mesenteric artery (SMA) lymph node regions and to examine the dose incidentally irradiated to the CA and SMA lymph node regions by involved-field radiation therapy (IFRT) for locally advanced pancreatic cancer (LAPC). Methods and Materials: Fifty-nine patients who had LAPC without distant metastasis were included. They received IFRT at 50.4 Gy in 28 fractions with 3-dimensional conformal radiation therapy. We calculated the percentages of overlap of GTV in the CA and SMA lymph node regions and examined what cases tend to have an overlap. We also investigated the dose metrics of CA and SMA lymph node regions by IFRT and the frequency of CA or SMA lymph node metastasis after IFRT. Results: The median GTV volume was 52.2 mL. Median overlap percentages in the CA and SMA lymph node regions were 39.2% and 28.6%, respectively. There was a significant correlation between GTV volume and SMA overlap percentage (P < .001). Although the SMA overlap percentage was higher in the pancreas head (P = .028), the CA overlap percentage was higher in the pancreas body or tail (P = .002). Median mean dose, D95, and minimum dose in the CA lymph node region were 50.1 Gy, 48.7 Gy, and 45.9 Gy, respectively, and those in the SMA lymph node region 49.9 Gy, 47.3 Gy, and 39.2 Gy, respectively. CA lymph node metastases after IFRT were detected in 4 patients (6.8%). Conclusions: An overlap between GTV and CA-SMA lymph node regions was detected in many patients, and the CA and SMA lymph node regions were irradiated incidentally even by IFRT. Prophylactic lymph node regions might not be necessary in radiation therapy planning of LAPC.

OBJECTIVE The authors aimed to investigate the dosimetric parameter and the minimally required dose associated with long-term control of sellar and parasellar tumors after Gamma Knife surgery (GKS) in children. METHODS A retrospective analysis was performed on pediatric patients younger than 19 years of age who were diagnosed with sellar and parasellar tumors and received GKS at the authors’ institution from 1998 to 2019. Cox proportional hazards regression analyses were used to investigate the dosimetric parameters associated with treatment outcome. The Kaplan-Meier method was used to analyze tumor control rates after GKS. RESULTS Overall, 37 patients with 40 sellar and parasellar tumors, including 22 craniopharyngiomas and 12 pituitary adenomas, had a mean follow-up of 85.8 months. The gross target volume was 0.05 cm3 to 15.28 cm3, and the mean marginal dose was 15.8 Gy (range 9.6–30.0 Gy). Ten patients experienced treatment failure at a mean of 28.0 ± 26.7 months. The actuarial 5- and 10-year tumor control rates were 79.0% and 69.8%, respectively. D98% was an independent predictive factor of tumor control (HR 0.846 [95% CI 0.749–0.956], p = 0.007), with a cutoff value of 11.5 Gy for the entire cohort and 10 Gy for the craniopharyngioma group. Visual deterioration occurred in 2 patients with the maximum point dose of 10.1 Gy and 10.6 Gy to the optic apparatus. CONCLUSIONS In pediatric patients, D98% was a reliable index of the minimum required dose for long-term control of sellar and parasellar tumors after GKS. The optimal D98% value for each tumor diagnosis needs to be elucidated in the future.

Radiotherapy is the main treatment method for nasopharynx cancer. Delineation of Gross Target Volume (GTV) from medical images is a prerequisite for radiotherapy. As manual delineation is time-consuming and laborious, automatic segmentation of GTV has a potential to improve the efficiency of this process. This work aims to automatically segment GTV of nasopharynx cancer from Computed Tomography (CT) images. However, it is challenged by the small target region, anisotropic resolution of clinical CT images, and the low contrast between the target region and surrounding soft tissues. To deal with these problems, we propose a 2.5D Convolutional Neural Network (CNN) to handle the different in-plane and through-plane resolutions. We also propose a spatial attention module to enable the network to focus on the small target, and use channel attention to further improve the segmentation performance. Moreover, we use a multi-scale sampling method for training so that the networks can learn features at different scales, which are combined with a multi-model ensemble method to improve the robustness of segmentation results. We also estimate the uncertainty of segmentation results based on our model ensemble, which is of great importance for indicating the reliability of automatic segmentation results for radiotherapy planning. Experiments with 2019 MICCAI StructSeg dataset showed that (1) Our proposed 2.5D network has a better performance on images with anisotropic resolution than the commonly used 3D networks. (2) Our attention mechanism can make the network pay more attention to the small GTV region and improve the segmentation accuracy. (3) The proposed multi-scale model ensemble achieves more robust results, and it can simultaneously obtain uncertainty information that can indicate potential mis-segmentations for better clinical decisions.

Although adaptive radiotherapy can reduce the negative dosimetric and clinical impacts of anatomical changes during head and neck treatments, evidence shows that it is not equally beneficial for all patients. This makes it important to electively schedule adaptation ahead of time to optimize clinical resources and patient benefit. The purpose of this study is to assess the feasibility of using both pre-treatment patient features and radiomic features extracted from a pre-treatment contrast enhanced computed tomography scan to predict the need for adaptive radiotherapy. Seventy-two patients were included in the analysis, of which 36 required adaptation. 36 pre-treatment semantic features as well as 351 radiomic features extracted from the gross target volume were considered. Three support vector machine models were developed: 1) considering only semantic features; 2) considering only radiomic features; 3) using a combination of features from 1 and 2. A robustness analysis of the selected radiomic features was also conducted. The best classification results were obtained considering 6 features (4 semantic and 2 radiomic) with median accuracy and area under the receiver operating characteristic curve of 0.821 and 0.843, respectively.

Background: High-grade gliomas (HGG) represent the commonest primary adult brain tumors. Radiotherapy plays an important role in the management of this disease. Objectives: To assess the patterns of failure, treatment-related toxicities, progression-free survival (PFS), and overall survival (OS), following limited-margins. Patients and Methods: In this prospective phase II study, patients with HGG have been treated with IMRT using the ESTRO-ACROP contouring guidelines that not include the peritumoral edema in the gross target volume (GTV) with adding 2cm margin around the GTV to create the clinical target volume (CTV), in one phase, after maximum safe resection of the tumor or stereotactic biopsy. Results: The trial included 40 patients with a median age of 49 years, 16 patients (40%) were in complete remission, 13 patients (12.5%) had partial regression, and stable disease occurred in 11 patients (27.5%). The progression/failure occurred in 28 patients (70%). Failures were located infield in 24 patients (86%), out-field in two patients (7%), and were marginal in two cases (7%). No notable serious toxicities during the treatment course; the commonest toxicities were G1-2 headache and vomiting (±72.5%). After a median follows up of 12.5 months; the median PFS and OS were 11.7 and 14.3 months respectively. Conclusion: In this study, the majority of relapses following limited volume IMRT occurred within the field of radiotherapy with acceptable treatment-related toxicity and oncological outcome, which suggest the use of IMRT with limited CTV as an acceptable treatment technique in HGG patients

Purpose The application value of 18F‐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, 18F‐FDG PET‐CT, and T2W‐MRI. Methods A total of 26 patients with thoracic esophageal cancer sequentially performed 3DCT, 4DCT, 18F‐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., Target volume delineation guided by multimodality images has become the key technology for precise radiotherapy of esophageal cancer. It may be a good choice to guide target delineation and construction of esophageal carcinoma by combining 4DCT with MRI imaging. There are significant differences for the GTVs in size and spatial position derived from T2W‐MRI and FDG‐PET/CT. Whereas, DW‐MRI could be used to replace PET‐CT for determining the upper and lower boundaries of esophageal carcinoma.

Radiotherapy plays an important role in the treatment of non-small cell lung cancer. Accurate segmentation of the gross target volume is very important for successful radiotherapy delivery. Deep learning techniques can obtain fast and accurate segmentation, which is independent of experts’ experience and saves time compared with manual delineation. In this paper, we introduce a modified version of ResNet and apply it to segment the gross target volume in computed tomography images of patients with non-small cell lung cancer. Normalization was applied to reduce the differences among images and data augmentation techniques were employed to further enrich the data of the training set. Two different residual convolutional blocks were used to efficiently extract the deep features of the computed tomography images, and the features from all levels of the ResNet were merged into a single output. This simple design achieved a fusion of deep semantic features and shallow appearance features to generate dense pixel outputs. The test loss tended to be stable after 50 training epochs, and the segmentation took 21 ms per computed tomography image. The average evaluation metrics were: Dice similarity coefficient, 0.73; Jaccard similarity coefficient, 0.68; true positive rate, 0.71; and false positive rate, 0.0012. Those results were better than those of U-Net, which was used as a benchmark. The modified ResNet directly extracted multi-scale context features from original input images. Thus, the proposed automatic segmentation method can quickly segment the gross target volume in non-small cell lung cancer cases and be applied to improve consistency in contouring.

Purpose To determine whether there are any changes in brain metastases or resection cavity volumes between planning magnetic resonance imaging (MRI) and radiosurgery (RS) treatment and whether these led to a change in management or alteration in the RS plan. Methods and Materials Patients undergoing RS for brain metastasis or tumor resection cavities had a standardized planning MRI (MRI-1) performed and a repeat verification MRI (MRI-2) 24 hours before RS. Any change in management, including replanning based on MRI-2, was recorded. Results Thirty-four patients with a total of 59 lesions (44 metastases and 15 tumor resection cavities) were assessed with a median time between MRI-1 and MRI-2 of 7 days. Seventeen patients (50%) required a change in management based on the changes seen on MRI-2. For patients with 7 days or less between scans, 41% (9 of 22) required a change in management; among patients with 8 days or more between scans, 78% (7 of 9) required a change in management. Per lesion, 32 out of 59 lesions required replanning, including 7 of 15 (47%) cavities and 25 of 44 (57%) metastases, with the most common reason (23 lesions) being an increase in gross target volume (tumor) or clinical target volume (tumor cavity). Conclusions Measurable changes occur in brain metastasis over a short amount of time, with a change in management required in 41% of patients with 7 days between MRI-1 and MRI-2 and in 78% of patients when there is a delay longer than 7 days. We therefore recommend that the time between planning MRI and RS treatment be as short as possible.

In this paper, we study the reliability of a novel deep learning framework for internal gross target volume (IGTV) delineation from 4-D computed tomography (4DCT), which is applied to patients with lung cancer treated by stereotactic body radiation therapy (SBRT). Seventy seven patients who underwent SBRT followed by 4DCT scans were incorporated in this retrospective study. The IGTV_DL was delineated using a novel deep machine learning algorithm with a linear exhaustive optimal combination framework. For the purpose of comparison, three other IGTVs based on common methods was also delineated. We compared the relative volume difference (RVI), matching index (MI), and encompassment index (EI) for the above IGTVs. Then, multiple parameter regression analysis was performed to assess the tumor volume and motion range as clinical influencing factors in the MI variation. The results demonstrated that the deep learning algorithm with linear exhaustive optimal combination framework has a higher probability of achieving optimal MI compared with other currently widely used methods. For patients after simple breathing training by keeping the respiratory frequency in 10 breath per minute (BPM), the four phase combinations of 0%, 30%, 50% and 90% can be considered as a potential solution for an optimal combination to synthesize IGTV in all respiration amplitudes.

Purpose/Objective(s) To evaluate the impact on decision making and radiotherapy (RT) treatment planning of brain metastases (BM) using gadopiclenol, a new gadolinium-based contrast agent (GBCA). Materials/Methods Patients who underwent two separate magnetic resonance imaging (MRI) examinations, one with gadopiclenol and one with gadobenate dimeglumine, both at 0.1 mmol/kg were included in the analysis. Those with ≥1 BM detected in any of both scans were subjected to a blinded reader analysis and contouring. For each patient, treatment plans (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]) were determined for both MRIs, with the gross target volume (GTV) indicating the contrast-enhancing aspects of the tumor. Mean GTVs and normal tissue volumes receiving 12 Gy (as well as the Dice similarity coefficient (DSC) were obtained for the paired contours. The Spearman´s rank (ρ) correlation was additionally calculated. Furthermore, 3 experts blindly of each lesion for contouring purposes and subjectively qualified them as “better”, in detriment of the counterpart, or “equal”. Results A total of 13 adult patients (31% females) presenting with at least one BM were analyzed. Gadopiclenol depicted additional BM as compared with gadobenate dimeglumine in 7 patients (54%). Treatment indication was changed in 2 (15%) patients, from no treatment to SRS and SRS to WBRT. The mean GTVs and V12 were comparable between gadopiclenol and gadobenate dimeglumine (P = 0.694, P = 1.974). The mean DSC was 0.70 (± 0.14, ρ 0.82). From a total 36 answers, an improvement in enhancement was qualified in 58.3% (n = 21) with g, while no difference was obtained in 19.4% (n = 7). Conclusion Gadopiclenol improved BM detection and characterization with impact on RT treatment decisions. Further trials are warranted to determine the impact of this novel MRI contrast agent on a clinical setting. Author Disclosure G.R. Sarria: Honoraria; Roche Pharma AG. Travel Expenses; Carl Zeiss Meditec AG. Volunteer; Rayos Contra Cancer Inc. J. Fleckenstein: None. M. Eckl: None. F. Stieler: None. M. Bendszus: None. L.C. Schmeel: None. D. Koch: None. A. Feist: None. M. Essig: None. F. Wenz: Honoraria; Carl Zeiss Meditec AG, Celgene GmbH, Roche Pharma AG, Eli Lilly and Co., Ipsen Pharma GmbH, Elekta AB.F.A. Giordano: Research Grant; Carl Zeiss Meditec AG, NOXXON Pharma AG. Honoraria; Implacit GmbH, Oncare GmbH, Roche Pharma AG, AstraZeneca GmbH.

Purpose: PET/CT is a standard medical imaging used in the delineation of gross tumor volume (GTV) in case of radiation therapy for lung tumors. However, PET/CT could present some limitations such as resolution and standardized uptake value threshold. Moreover, chest MRI has shown good potential in diagnosis for thoracic oncology. Therefore, we investigated the influence of chest MRI on inter-observer variability of GTV delineation. Methods and Materials: Five observers contoured the GTV on CT for 14 poorly defined lung tumors during three contouring phases based on true daily clinical routine and acquisition: CT phase, with only CT images; PET phase, with PET/CT; and MRI phase, with both PET/CT and MRI. Observers waited at least 1 week between each phases to decrease memory bias. Contours were compared using descriptive statistics of volume, coefficient of variation (COV), and Dice similarity coefficient (DSC). Results: MRI phase volumes (median 4.8 cm3) were significantly smaller than PET phase volumes (median 6.4 cm3, p = 0.015), but not different from CT phase volumes (median 5.7 cm3, p = 0.30). The mean COV was improved for the MRI phase (0.38) compared to the CT (0.58, p = 0.024) and PET (0.53, p = 0.060) phases. The mean DSC of the MRI phase (0.67) was superior to those of the CT and PET phases (0.56 and 0.60, respectively; p < 0.001 for both). Conclusions: The addition of chest MRI seems to decrease inter-observer variability of GTV delineation for poorly defined lung tumors compared to PET/CT alone and should be explored in further prospective studies.

Background: To determine optimum conditions for diagnosis of nasopharyngeal carcinoma, we established VX2 rabbit model to delineate gross target volume (GTV) in different imaging methods. Methods: The orthotopic nasopharyngeal carcinoma (NPC) was established in sixteen New Zealand rabbits. After 7-days inoculation, the rabbits were examined by CT scanning and then sacrificed for pathological examination. To achieve best delineation, different GTVs of CT, MRI, 18F-FDG PET/CT, and 18F-FLT PET/CT images were correlated with pathological GTV (GTVp). Findings: We found a 45% and 60% of the maximum standardized uptake value (SUVmax) as the optimal SUV threshold for the target volume of NPC in 18F-FDG PET/CT and 18F-FLT PET/CT images, respectively (GTVFDG45% and GTVFLT60%). Moreover, the GTVMRI and GTVCT were significantly higher than the GTVp (P ≤ 0.05), while the GTVFDG45% and especially GTVFLT60% were similar to the GTVp (R = 0.892 and R = 0.902, respectively; P ≤ 0.001). Interpretation: Notably, the results suggested that 18F-FLT PET/CT could reflect the tumor boundaries more accurately than 18F-FDG PET/CT, MRI and CT, which makes 18F-FLT PET-CT more advantageous for the clinical delineation of the target volume in NPC. Funding Statement: This research received financial support from the Scientific Research Project Fund of the Affiliated Hospital of Southwest Medical University (2013-60). Declaration of Interests: The authors have no financial interests related to the material in the manuscript. The authors declare that there are no conflicts of interest. Ethics Approval Statement: This study was approved by an independent ethics committee/institutional review board at Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. All animal-related procedures and protocol were approved under the guidelines of the National Institutes of Health (NIH) Animal Care (1995, USA) and the local Ethics Committee guidelines by Institutional Animal Care and Treatment Committee of Southwest Medical University (Luzhou, China).

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.

Background and purpose: The gross tumour volume (GTV) is predictive of clinical outcome and consequently features in many machine-learned models. 4D-planning, however, has prompted substitution of the GTV with the internal gross target volume (iGTV). We present and validate a method to synthesise GTV data from the iGTV, allowing the combination of 3D and 4D planned patient cohorts for modelling. Material and methods: Expert delineations in 40 non-small cell lung cancer patients were used to develop linear fit and erosion methods to synthesise the GTV volume and shape. Quality was assessed using Dice Similarity Coefficients (DSC) and closest point measurements; by calculating dosimetric features; and by assessing the quality of random forest models built on patient populations with and without synthetic GTVs. Results: Volume estimates were within the magnitudes of inter-observer delineation variability. Shape comparisons produced mean DSCs of 0.8817 and 0.8584 for upper and lower lobe cases, respectively. A model trained on combined true and synthetic data performed significantly better than models trained on GTV alone, or combined GTV and iGTV data. Conclusions: Accurate synthesis of GTV size from the iGTV permits the combination of lung cancer patient cohorts, facilitating machine learning applications in thoracic radiotherapy. (C) 2017 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 126 (2018) 355-361

A Phase II study was designed to test the safety and efficacy of concurrent chemoradiotherapy with a modified target volumes delineation method for inoperable oesophageal cancer patients.All eligible patients were treated with concurrent chemoradiotherapy. The method of delineating target volume is as follows: Planning gross target volume (PGTV) was defined as the primary gross tumour volume (GTV-t) plus a 3 cm margin longitudinally and a 0.5 cm margin circumferentially, and positive lymph nodes(GTV-n) plus a 0.5 cm margin in all directions. Clinical target volume (CTV) was defined as PGTV plus a 0.5 cm margin in all directions and elective nodal region. Planning target volume (PTV) was defined as CTV plus a 0.5 cm margin in all directions. The dose of PGTV is 54-60 Gy in 27-30 fractions(2Gy per fraction). The dose of PTV is 48.6-54 Gy in 27-30 fractions(1.8Gy per fraction). The regimen consists of paclitaxel135 mgm34 patients were enrolled in this study. The median follow-up time was 20.9 months (range: 3.7-28.4 months) for all patients. The 1- and 2-year survival rates for all patients were 70.5 and 44.1%, respectively. Clinical complete response was observed in 21 patients(61.8%), cPR was observed in 9 patients(26.5%) and cSD was observed in 4 patients(11.7%).This modified method with concurrent chemotherapy could achieve better locoregional control rate. The 1- and 2-year survival rates of this method were close to the survival rates of the current methods widely adopted. Advances in knowledge: The modified target volumes delineation method can enhance locoregional control rate of concurrent chemoradiotherapy.

Purpose: To investigate the difference in sparing normal livertissue between 4D‐CT and active breathing coordinator (ABC) in the radiotherapy of Hepatocellular carcinoma(HCC) applying RapidArc. Methods: Ten patients with HCC underwent 3D‐CT at end inspiration hold(EIH) associated with active breathing coordinator(ABC) ,and 4D‐CT scan. The 4D‐CT images were sorted in to 10 serious CTimages according respiratory phase. Gross tumor volumes(GTVs) were manually contoured on different CTimages. The individual internal gross target volume(IGTV) was obtained from 10 GTVs of 4D‐CT images. Plan target volumes (PTVs) were obtained based on IGTV and GTVEIH. PTV1 was obtained from IGTV plus 5 mm margins isotropically, and PTV2 was obtained from GTVEIH using 8 mm margins isotropically. RapidArc plans were designed on PTV1 and PTV2, for PTV1 RapidArc plans with one single whole arc were applied and for PTV2 three 135°arcs, and name RapidArc1 and RapidArc2. Dosimetric differences were compared. Results: There were no significant difference in conformity index (0.93±0.05 Vs 0.93±0.03), homogeneity index(1.08±0.01 Vs 1.08±0.01) , the Dl%(54.44±0.36 Gy Vs54.68±0.47 Gy) and D99%(49.18±0.48Gy Vs 49.00±0.34 Gy) between RapidArc1 and RapidArc2(P>0.05). There were no significant differences in the mean dose(8.23±1.5Gy Vs 7.63±3.00Gy),V5(46.64±19.31Vs43.29±19.94), V10(28.73±11.54 Vs 28.23±12.37), V15(17.87±6.61 Vs 18.20±7.55), V20(11.62±4.39 Vs 11.83±4.58), V25(7.71±2.91Vs 7.58±2.79),V30(5.14±2.01Vs5.05±1.79), 35(3.41±1.35Vs 3.35±1.21) and V40(2.12±0.86Vs2.06±0.75) between RapidArc1 and RapidArc2 (P>0.05). Conclusions: The RapidArc plans with three 135°arcs associated could achieve similar dose delivery as the plans with single whole arc, and 4D‐CT and ABC could play similar role in sparing normal livertissue assuring the accuracy of target volume in radiotherapy of HCC.

To achieve consistent target delineation in radiotherapy for hepatocellular carcinoma (HCC), image registration between simulation CT and diagnostic MRI was explored. Twenty patients with advanced HCC were included. The median interval between MRI and CT was 11 days. CT was obtained with shallow free breathing and MRI at exhale phase. On each CT and MRI, the liver and the gross target volume (GTV) were drawn. A rigid image registration was taken according to point information of vascular bifurcation (Method[A]) and pixel information of volume of interest only including the periphery of the liver (Method[B]) and manually drawn liver (Method[C]). In nine cases with an indefinite GTV on CT, a virtual sphere was generated at the epicenter of the GTV. The GTV from CT (V GTV [CT]) and MRI (V GTV [MR]) and the expanded GTV from MRI (V +GTV [MR]) considering geometrical registration error were defined. The underestimation (uncovered V[CT] by V[MR]) and the overestimation (excessive V[MR] by V[CT]) were calculated. Through a paired T -test, the difference between image registration techniques was analyzed. For method[A], the underestimation rates of V GTV [MR] and V +GTV [MR] were 16.4 ± 8.9% and 3.2 ± 3.7%, and the overestimation rates were 16.6 ± 8.7% and 28.4 ± 10.3%, respectively. For V GTV [MR] and V +GTV [MR], the underestimation rates and overestimation rates of method[A] were better than method[C]. The underestimation rates and overestimation rates of the V GTV [MR] were better in method[B] than method[C]. By image registration and additional margin, about 97% of HCC could be covered. Method[A] or method[B] could be recommended according to physician preference.

To compare the rectal tumour gross target volume (GTV) delineated on T2 weighted (T2W MRI) and diffusion weighted MRI (DWI) images by two different observers and to assess if agreement is improved by DWI.27 consecutive patients (15 male, range 27.1-88.8 years, mean 66.9 years) underwent 1.5T MRI prior to chemoradiation (45Gy in 25 fractions; oral capecitabine 850mg/m(2)), including axial T2W MRI (TR=6600ms, TE=90ms) and DWI (TR=3000ms, TE=77ms, b=0, 100, 800s/mm(2)). 3D tumour volume (cm(3)) was measured by volume of interest (VOI) analysis by two independent readers for the T2W MRI and b800 DWI axial images, and the T2W MRI and DWI volumes compared using Mann-Whitney test. Observer agreement was assessed using Bland-Altman statistics. Significance was at 5%.Artefacts precluded DWI analysis in 1 patient. In the remaining 26 patients evaluated, median (range) T2W MRI MRI and DWI (b=800s/mm(2)) 3D GTVin cm(3) were 33.97 (4.44-199.8) and 31.38 (2.43-228), respectively, for Reader One and 43.78 (7.57-267.7) and 42.45 (3.68-251) for Reader Two. T2W MRI GTVs were slightly larger but not statistically different from DWI volumes: p=0.52 Reader One; p=0.92 Reader Two. Interobserver mean difference (95% limits of agreement) for T2W MRI and DWI GTVs were -9.84 (-54.96 to +35.28) cm(3) and -14.79 (-54.01 to +24.43) cm(3) respectively.Smaller DWI volumes may result from better tumour conspicuity but overall observer agreement is not improved by DWI.

127 Background: To determine the optimum conditions for diagnosis of nasopharyngeal carcinoma, we established VX2 rabbit model to delineate gross target volume (GTV) in different imaging methods. Methods:The orthotopic nasopharyngeal carcinoma (NPC) was established in sixteen New Zealand rabbits. After 7-days inoculation, the rabbits were examined by CT scanning and then sacrificed for pathological examination. To achieve the best delineation, different GTVs of CT, MRI, 18F-FDG PET/CT, and 18F-FLT PET/CT images were correlated with pathological GTV (GTVp). Results: We found 45% and 60% of the maximum standardized uptake value (SUVmax) as the optimal SUV threshold for the target volume of NPC in 18F-FDG PET/CT and 18F-FLT PET/CT images, respectively (GTVFDG45% and GTVFLT60%). Moreover, the GTVMRI and GTVCT were significantly higher than the GTVp ( P ≤ 0.05), while the GTVFDG45% and especially GTVFLT60% were similar to the GTVp ( R = 0.892 and R = 0.902, respectively; P ≤ 0.001). Conclusions: Notably, the results suggested that 18F-FLT PET/CT could reflect the tumor boundaries more accurately than 18F-FDG PET/CT, MRI and CT, which makes 18F-FLT PET-CT more advantageous for the clinical delineation of the target volume in NPC. Keywords: Nasopharyngeal carcinoma; Gross tumor volume; Magnetic resonance imaging, Computed tomography; 18F-FLT PET/CT; 18F-FDG PET/CT

The background of this study is to evaluate 3D dose distribution in organs at risk (OARs). The sample of the study consists of 300 patients; with age-range mean and standard deviation (35 ± 2.32 respectively). The CT simulator was used to collect data to delineate pituitary adenoma including growth target volume (GTV) and planning target volume (PTV 95%) as an isodose line for treatment protocol in order to obtain dose distribution of 3D dose coverage to the target while sparing organs at risks. The main results of this study were, 3D dose distribution is safe, because it confines the dose to gross target volume only, while sparing escalating dose to the organ at risks (OARs), the average dose reaching the organs at risks during the pituitary adenoma to the adjacent critical organs are such as: in temporal lobe is 1.14 Gy, in eye is 0.86 Gy, and in optic chiasm is 0.95 Gy. Therefore, it is concluded that the 3D dose distribution in pituitary adenoma treatment reduces an unnecessary radiation to critical organs. Thus, new technique needs to be developed to halt an unnecessary dose reaching organs at risks during treatment.

The purpose of the study is to evaluate the two dimensional dose distribution techniques in pituitary adenoma patient treatment in order to provide 2D dose coverage to the target volume while sparing organs at risk (OARs). The CT simulator was used to radiograph 300 patients of pituitary adenomas to conform 2D dose distribution planning inside the tumour bed , and its structures were delineated; including gross target volume (GTV), clinical target volume (CTV), and planning target volume (PTV)), as well as organs at risks (OARs) . Dose distribution analysis was edited to provide 2D dose coverage to the target while sparing organs at risk. The main results of the study were, 2D dose distribution plans increases the unnecessary dose to the critical organs according to their geographical location from the pituitary adenoma site, and the present study , concludes that when the tumour dose increases from 45 to 55 Gy there is a linear proportional increment of dose to the organs at risks, and when the dose is about 60 Gy in 2D, the increment of unnecessary dose to temporal lobe is 0.31 Gy, and to eye is0.34Gy, and to optic chiasm is 0.42 Gy respectively .New techniques, which will lessen the unnecessary dose to OARs, needed to be developed .

Radiotherapy is a major modality in the treatment of brain tumours. The target volumes definition has to be precise for the radiation planification. The gross target volume (GTV) is most of the time delineated within the fusion of the planning CT scan with the appropriated MRI sequences. The clinical target volume (CTV) definition is more complex: it varies in time following the evolution of scientific knowledge and also depending of the school of thought. This article offers a review of the literature about the margins applied in brain tumours radiotherapy for gliomas (high grade, anaplastic, low grade and brain stem gliomas), embryologic tumours (medulloblastomas and primitive neuroectodermal tumours [PNET]), ependymomas, atypical teratoid rahbdoid tumours (ATRT), craniopharyngiomas, pineal gland tumours, primary central nervous cell lymphomas, meningiomas and schwannomas. New imaging modalities such as diffusion-weighted imaging, dynamic contrast enhanced, spectroscopic MRI and PET scan will allow us to delineate more precisely the target volumes and to realise dose-painting by adapting the dose to the tumour metabolism.

Purpose To compare analytic and Monte Carlo–based algorithms for proton dose calculations in the lung, benchmarked against anthropomorphic lung phantom measurements. Methods and Materials A heterogeneous anthropomorphic moving lung phantom has been irradiated at numerous proton therapy centers. At 5 centers the treatment plan could be calculated with both an analytic and Monte Carlo algorithm. The doses calculated in the treatment plans were compared with the doses delivered to the phantoms, which were measured using thermoluminescent dosimeters and film. Point doses were compared, as were planar doses using a gamma analysis. Results The analytic algorithms overestimated the dose to the center of the target by an average of 7.2%, whereas the Monte Carlo algorithms were within 1.6% of the physical measurements on average. In some regions of the target volume, the analytic algorithm calculations differed from the measurement by up to 31% in the internal gross target volume (iGTV) (46% in the planning target volume), over-predicting the dose. All comparisons showed a region of at least 15% dose discrepancy within the iGTV between the analytic calculation and the measured dose. The Monte Carlo algorithm recalculations showed dramatically improved agreement with the measured doses, showing mean agreement within 4% for all cases and a maximum difference of 12% within the iGTV. Conclusions Analytic algorithms often do a poor job predicting proton dose in lung tumors, over-predicting the dose to the target by up to 46%, and should not be used unless extensive validation counters the consistent results of the present study. Monte Carlo algorithms showed dramatically improved agreement with physical measurements and should be implemented to better reflect actual delivered dose distributions.

Aim This study represents an enumeration and comparison of gross target volumes (GTV) as delineated independently on contrast-enhanced computed tomography (CT) and T1 and T2 weighted magnetic resonance imaging (MRI) in vestibular schwannomas (VS). Background Multiple imaging in radiotherapy improves target localization. Methods and materials 42 patients of VS were considered for this prospective study with one patient showing bilateral tumor. The GTV was delineated separately on CT and MRI. Difference in volumes were estimated individually for all the 43 lesions and similarity was studied between CT and T1 and T2 weighted MRI. Results The male to female ratio for VS was found to be 1:1.3. The tumor was right sided in 34.9% and left sided in 65.1%. Tumor volumes (TV) on CT image sets were ranging from 0.251 cc to 27.27 cc. The TV for CT, MRI T1 and T2 weighted were 5.15 ± 5.2 cc, 5.8 ± 6.23 cc, and 5.9 ± 6.13 cc, respectively. Compared to MRI, CT underestimated the volumes. The mean dice coefficient between CT versus T1 and CT versus T2 was estimated to be 68.85 ± 18.3 and 66.68 ± 20.3, respectively. The percentage of volume difference between CT and MRI (%VD: mean ± SD for T1; 28.84 ± 15.0, T2; 35.74 ± 16.3) and volume error (%VE: T1; 18.77 ± 10.1, T2; 23.17 ± 13.93) were found to be significant, taking the CT volumes as the baseline. Conclusions MRI with multiple sequences should be incorporated for tumor volume delineation and they provide a clear boundary between the tumor and normal tissue with critical structures nearby.

Background Gross target volume of primary tumor (GTV-P) is very important for the prognosis prediction of patients with nasopharyngeal carcinoma (NPC), but it is unknown whether the same is true for locally advanced NPC patients treated with intensity-modulated radiotherapy (IMRT). This study aimed to clarify the prognostic value of tumor volume for patient with locally advanced NPC receiving IMRT and to find a suitable cut-off value of GTV-P for prognosis prediction. Methods Clinical data of 358 patients with locally advanced NPC who received IMRT were reviewed. Receiver operating characteristic (ROC) curves were used to identify the cut-off values of GTV-P for the prediction of different endpoints [overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS)] and to test the prognostic value of GTV-P when compared with that of the American Joint Committee on Cancer T staging system. Results The 358 patients with locally advanced NPC were divided into two groups by the cut-off value of GTV-P as determined using ROC curves: 219 (61.2%) patients with GTV-P ≤46.4 mL and 139 (38.8%) with GTV-P >46.4 mL. The 3-year OS, LRFS, DMFS, and DFS rates were all higher in patients with GTV-P ≤46.4 mL than in those with GTV-P > 46.4 mL (all P 46.4 mL was an independent unfavorable prognostic factor for patient survival. The ROC curve verified that the predictive ability of GTV-P was superior to that of T category (P 46.4 mL is an independent unfavorable prognostic indicator for survival after IMRT, with a prognostic value superior to that of T category.

Background The purpose of this study was to assess the efficacy and toxicities of reirradiation using intensity-modulated radiotherapy (IMRT) in patients with locally advanced recurrent nasopharyngeal carcinoma (NPC). Methods Thirty-eight patients with consecutive rT3 to rT4 NPC treated between 2005 and 2013 were retrospectively analyzed. Results The 3-year overall survival (OS), progression-free survival (PFS), and local control rate were 47.2%, 17.5%, and 44.3%, respectively. Gross target volume (GTV) D95, GTV D50, and age were all important prognostic factors for OS and PFS, but only GTV D95 was an important determinant for local control. A total of 73.7% patients experienced ≥1 grade 3 late toxicities and 3 patients died of massive epistaxis. Temporal lobe necrosis (TLN) developed sooner with a higher total biological equivalent dose. Conclusion Adequate tumor dose coverage was important for treating rT3 to rT4 NPC. Although late complications were common, treatment-related mortality was solely vascular in nature. Dose constraints of neurologic structures for reirradiation should be revised with the latest information on late toxicities. © 2016 Wiley Periodicals, Inc. Head Neck, 2016