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As a component of myeloablative conditioning before allogeneic hematopoietic stem cell transplantation (HSCT), Total Body Irradiation (TBI) is employed in radiotherapy centers all over the world. In recent and coming years, many centers are changing their technical setup from a conventional TBI technique to multi-isocenter conformal arc therapy techniques such as Volumetric Modulated Arc Therapy (VMAT) or Helical Tomotherapy (HT). These techniques allow better homogeneity and control of the target prescription dose, and provide more freedom for individualized organ-at-risk sparing. The technical design of multi-isocenter/multi-plan conformal TBI is complex and should be developed carefully. A group of early adopters with conformal TBI experience using different treatment machines and treatment planning systems came together to develop technical recommendations and share experiences, in order to assist departments wishing to implement conformal TBI, and to provide ideas for standardization of practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Post-operative radiosurgery (SRS) of brain metastases patients is typically planned on a post-recovery MRI, 2-4 weeks after resection. However, the intracranial metastasis may (re-)grow in this period. Planning SRS directly on the post-operative MRI enables shortening this time interval, anticipating the start of adjuvant systemic therapy, and so decreasing the chance of extracranial progression. The MRI-Linac (MRL) allows the simultaneous execution of the post-operative MRI and SRS treatment. The aim of this work was investigating the dosimetric feasibility of MRL-based post-operative SRS., Methods: MRL treatments based on the direct post-operative MRI were simulated, including thirteen patients with resectable single brain metastases. The gross tumor volume (GTV) was contoured on the direct post-operative scans and compared to the post-recovery MRI GTV. Three plans for each patient were created: a non-coplanar VMAT CT-Linac plan (ncVMAT) and a coplanar IMRT MRL plan (cIMRT) on the direct post-operative MRI, and a ncVMAT plan on the post-recovery MRI as the current clinical standard., Results: Between the direct post-operative and post-recovery MRI, 15.5 % of the cavities shrunk by > 2 cc, and 46 % expanded by ≥ 2 cc. Although the direct post-operative cIMRT plans had a higher median gradient index (3.6 vs 2.7) and median V3Gy of the skin (18.4 vs 1.1 cc) compared to ncVMAT plans, they were clinically acceptable., Conclusion: Direct post-operative MRL-based SRS for resection cavities of brain metastases is dosimetrically acceptable, with the advantages of increased patient comfort and logistics. Clinical benefit of this workflow should be investigated given the dosimetric plausibility., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Myeloablative Total Body Irradiation (TBI) is an important modality in conditioning for allogeneic hematopoietic stem cell transplantation (HSCT), especially in children with high-risk acute lymphoblastic leukemia (ALL). TBI practices are heterogeneous and institution-specific. Since TBI is associated with multiple late adverse effects, recommendations may help to standardize practices and improve the outcome versus toxicity ratio for children., Material and Methods: The European Society for Paediatric Oncology (SIOPE) Radiotherapy TBI Working Group together with ESTRO experts conducted a literature search and evaluation regarding myeloablative TBI techniques and toxicities in children. Findings were discussed in bimonthly virtual meetings and consensus recommendations were established., Results: Myeloablative TBI in HSCT conditioning is mostly performed for high-risk ALL patients or patients with recurring hematologic malignancies. TBI is discouraged in children <3-4 years old because of increased toxicity risk. Publications regarding TBI are mostly retrospective studies with level III-IV evidence. Preferential TBI dose in children is 12-14.4 Gy in 1.6-2 Gy fractions b.i.d. Dose reduction should be considered for the lungs to <8 Gy, for the kidneys to ≤10 Gy, and for the lenses to <12 Gy, for dose rates ≥6 cGy/min. Highly conformal techniques i.e. TomoTherapy and VMAT TBI or Total Marrow (and/or Lymphoid) Irradiation as implemented in several centers, improve dose homogeneity and organ sparing, and should be evaluated in studies., Conclusions: These ESTRO ACROP SIOPE recommendations provide expert consensus for conventional and highly conformal myeloablative TBI in children, as well as a supporting literature overview of TBI techniques and toxicities., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The aim of this study was to determine the feasibility of hypofractionated schedules for metastatic bone/bone marrow lesions in children and to investigate dosimetric differences to the healthy surrounding tissues compared to conventional schedules., Methods: 27 paediatric patients (mean age, 7 years) with 50 metastatic bone/bone marrow lesions (n = 26 cranial, n = 24 extra-cranial) from solid primary tumours (neuroblastoma and sarcoma) were included. The PTV was a 2 mm expansion of the GTV. A prescription dose of 36 and 54 Gy EQD2 α / β =10 was used for neuroblastoma and sarcoma lesions, respectively. VMAT plans were optimized for each single lesion using different fractionation schedules: conventional (30/20 fractions, V 95%  ≥ 99%, D 0.1cm 3  ≤ 107%) and hypofractionated (15/10/5/3 fractions, V 100% ≥ 95%, D 0.1cm 3  ≤ 120%) . Relative EQD2 differences in OARs D mean between the different schedules were compared., Results: PTV coverage was met for all plans independently of the fractionation schedule and for all lesions (V 95% range 95.5-100%, V 100% range 95.1-100%), with exception of the vertebrae (V 100% range 63.5-91.0%). For most OARs, relative mean reduction in the D mean was seen for the hypofractionated plans compared to the conventional plans, with largest sparing in the 5 fractions (< 43%) followed by the 3 fractions schedule (< 40%). In case of PTV overlap with an OAR, a significant increase in dose for the OAR was observed with hypofractionation., Conclusions: For the majority of the cases, iso-effective plans with hypofractionation were feasible with similar or less dose in the OARs. The most suitable fractionation schedule should be personalised depending on the spatial relationship between the PTV and OARs and the prescription dose., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: In pediatric renal tumors, conventional two opposing photon beams have been used to cover the postoperative flank target volume for decades. This single center study describes the locoregional outcome using highly conformal flank target volumes adjusted for postoperative changes and intra-fraction motion combined with Volumetric-Modulated Arc Therapy (VMAT)., Materials and Methods: Between 01-2015 and 12-2019, 36/161 newly diagnosed patients with renal tumors underwent flank only irradiation (n = 30) or flank + whole lung irradiation (n = 6) using highly conformal target volumes in line with the SIOP-RTSG consensus statement. VMAT consisted of full-arc 10MV photon beams optimized for constraints of the organs at risk. In case of locoregional relapses, image co-registration and dose reconstruction was performed. Each relapse was classified as either 'infield' (V95% relapse : ≥99.0%), 'marginal' (V95% relapse : 20.0-98.9%) or 'outfield' (V95% relapse : 0-19.9%)., Results: At a median follow-up from diagnosis of 3.1 years (range:0.4-5.7), the estimated 2-year Locoregional Control Rate, Disease-Free Interval and Overall Survival were 94%, 91% and 94%, respectively. Locoregional relapse was observed in two patients. One patient had a combined tumor bed and regional recurrence, classified as infield (V95% relapse : 100%) and outfield (V95% relapse : 1.2%). The second patient had a regional relapse in the inferior vena cava classified as marginal recurrence (V95% relapse : 93%). Relapses would not have been adequately covered by conventional beams., Conclusions: This single center analysis provides encouraging evidence that excellent locoregional control can be obtained by using highly conformal flank target volumes with VMAT in pediatric renal tumors. The safety of this approach will be validated in a prospective multicenter study., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Dose prediction using deep learning networks prior to radiotherapy might lead tomore efficient modality selections. The study goal was to predict proton and photon dose distributions based on the patient-specific anatomy and to assess their clinical usage for paediatric abdominal tumours., Material and Methods: Data from 80 patients with neuroblastoma or Wilms' tumour was included. Pencil beam scanning (PBS) (5 mm/ 3%) and volumetric-modulated arc therapy (VMAT) plans (5 mm) were robustly optimized on the internal target volume (ITV). Separate 3-dimensional patch-based U-net networks were trained to predict PBS and VMAT dose distributions. Doses, planning-computed tomography images and relevant optimization masks (ITV, vertebra and organs-at-risk) of 60 patients were used for training with a 5-fold cross validation. The networks' performance was evaluated by computing the relative error between planned and predicted dose-volume histogram (DVH) parameters for 20 inference patients. In addition, the organs-at-risk mean dose difference between modalities was calculated using planned and predicted dose distributions (ΔD mean  = D VMAT -D PBS ). Two radiation oncologists performed a blind PBS/VMAT modality selection based on either planned or predicted ΔD mean ., Results: Average DVH differences between planned and predicted dose distributions were ≤ |6%| for both modalities. The networks classified the organs-at-risk D mean difference as a gain (ΔD mean  > 0) with 98% precision. An identical modality selection based on planned compared to predicted ΔD mean was made for 18/20 patients., Conclusion: Deep learning networks for accurate prediction of proton and photon dose distributions for abdominal paediatric tumours were established. These networks allowing fast dose visualisation might aid in identifying the optimal radiotherapy technique when experience and/or resources are unavailable., Competing Interests: Declaration of Competing Interest The authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Two-opposing photon beams are considered standard of care for flank irradiation in pediatric patients with renal tumors. Nowadays, Image-Guided Radiotherapy (IGRT) techniques allow high-precision dose delivery to complex flank target volumes taking into account postoperative organ shifts and tumor bed motion. This study examines the contribution of a lateral and superior surgical clip on flank target volume delineation intended for IGRT., Methods: Between 01-2015 and 09-2019, 30/162 newly-diagnosed pediatric patients with renal tumors, lateral/superior surgical clips (n = 30/30) and available 4D-CT-scans (n = 27/30), underwent postoperative flank irradiation. The lateral and superior clip, as respective markers for the lateral tumor extension and intrafraction motion, were analyzed. The positive and negative values depict the lateral/dorsal/cranial or the medial/ventral/caudal direction, respectively. Planning target volumes (PTV) were generated based on lateral clips (PTV latclip ), superior clips with 4D-CT technology (PTV supclip ), and both clips combined (PTV combined ), and compared to an approach without clips (PTV noclip )., Results: Indicated by clips, the mean lateral tumor bed extension along the posterior wall was 74° (range: 50°-93°), while mean intrafraction motion was +1.2 mm (range: -1.8/+4.8 mm), +0.6 mm (range: +0.6/+4.9 mm), -0.3 mm (range: -3.8/+0.7 mm) in craniocaudal, ventrodorsal, mediolateral direction, respectively. The median PTV noclip (556 mL) was statistically different from the median PTV latclip (454 mL, p = <0.01), median PTV supclip (373 mL, p = <0.01) and median PTV combined (348 mL p = <0.01)., Conclusion: In pediatric patients with renal tumors, surgical clips at the lateral and superior border of the tumor bed can optimize flank target volume delineation and, consequently, reduce the normal tissue volume receiving high-dose irradiation when IGRT techniques are applied., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: To reduce relapse risk, Total Body Irradiation (TBI) is part of conditioning regimens for hematopoietic stem cell transplantation (HSCT) in pediatric acute leukemia. The study purpose was to evaluate clinical practices regarding TBI, such as fractionation, organ shielding and delivery techniques, among SIOPE affiliated radiotherapy centers., Methods: An electronic survey was sent out to 233 SIOPE affiliated centers, containing 57 questions about clinical practice of TBI. Surveys could be answered anonymously., Results: From over 25 countries, 82 responses were collected. For TBI-performing centers, 40/48 irradiated ≤10 pediatric patients annually (range: 1-2 to >25). Most indications concerned acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Four different fractionation schedules were used, of which 12 Gy in 6 fractions was applied in 91% for ALL and 86% for AML. Dose reduction to the lungs, mostly to a mean dose of 8-10 Gy, was applied by 28/33 centers for ALL and 19/21 centers for AML, in contrast to much less applied dose reduction to the kidneys (7/33 ALL and 7/21 AML), thyroid (2/33 ALL and 2/21 AML), liver (4/33 ALL and 3/21 AML) and lenses (4/33 ALL and 4/21 AML). Conventional TBI techniques were used by 24/29 responding centers, while 5/29 used advanced optimized planning techniques., Conclusion: Across SIOPE, there is a high level of uniformity in fractionation and use of lung shielding. Practices vary regarding other organs-at-risk shielding and implementation of advanced techniques. A SIOPE radiotherapy working group will be established to define international guidelines for pediatric TBI., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To assess the feasibility of magnetic resonance imaging (MRI)-only treatment planning for photon and proton radiotherapy in children with abdominal tumours., Materials and Methods: The study was conducted on 66 paediatric patients with Wilms' tumour or neuroblastoma (age 4 ± 2 years) who underwent MR and computed tomography (CT) acquisition on the same day as part of the clinical protocol. MRI intensities were converted to CT Hounsfield units (HU) by means of a UNet-like neural network trained to generate synthetic CT (sCT) from T1- and T2-weighted MR images. The CT-to-sCT image similarity was evaluated by computing the mean error (ME), mean absolute error (MAE), peak signal-to-noise ratio (PSNR) and Dice similarity coefficient (DSC). Synthetic CT dosimetric accuracy was verified against CT-based dose distributions for volumetric-modulated arc therapy (VMAT) and intensity-modulated pencil-beam scanning (PBS). Relative dose differences (D diff ) in the internal target volume and organs-at-risk were computed and a three-dimensional gamma analysis (2 mm, 2%) was performed., Results: The average ± standard deviation ME was -5 ± 12 HU, MAE was 57 ± 12 HU, PSNR was 30.3 ± 1.6 dB and DSC was 76 ± 8% for bones and 92 ± 9% for lungs. Average D diff were <0.5% for both VMAT (range [-2.5; 2.4]%) and PBS (range [-2.7; 3.7]%) dose distributions. The average gamma pass-rates were >99% (range [85; 100]%) for VMAT and >96% (range [87; 100]%) for PBS., Conclusion: The deep learning-based model generated accurate sCT from planning T1w- and T2w-MR images. Most dosimetric differences were within clinically acceptable criteria for photon and proton radiotherapy, demonstrating the feasibility of an MRI-only workflow for paediatric patients with abdominal tumours., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. van Stralen and P.R. Seevinck are minority shareholders at MRIguidance B.V., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: To enable accurate magnetic resonance imaging (MRI)-based dose calculations, synthetic computed tomography (sCT) images need to be generated. We aim at assessing the feasibility of dose calculations from MRI acquired with a heterogeneous set of imaging protocol for paediatric patients affected by brain tumours., Materials and Methods: Sixty paediatric patients undergoing brain radiotherapy were included. MR imaging protocols varied among patients, and data heterogeneity was maintained in train/validation/test sets. Three 2D conditional generative adversarial networks (cGANs) were trained to generate sCT from T1-weighted MRI, considering the three orthogonal planes and its combination (multi-plane sCT). For each patient, median and standard deviation (σ) of the three views were calculated, obtaining a combined sCT and a proxy for uncertainty map, respectively. The sCTs were evaluated against the planning CT in terms of image similarity and accuracy for photon and proton dose calculations., Results: A mean absolute error of 61 ± 14 HU (mean±1σ) was obtained in the intersection of the body contours between CT and sCT. The combined multi-plane sCTs performed better than sCTs from any single plane. Uncertainty maps highlighted that multi-plane sCTs differed at the body contours and air cavities. A dose difference of -0.1 ± 0.3% and 0.1 ± 0.4% was obtained on the D > 90% of the prescribed dose and mean γ 2%,2mm pass-rate of 99.5 ± 0.8% and 99.2 ± 1.1% for photon and proton planning, respectively., Conclusion: Accurate MR-based dose calculation using a combination of three orthogonal planes for sCT generation is feasible for paediatric brain cancer patients, even when training on a heterogeneous dataset., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: To evaluate the dosimetric sparing and robustness against inter-fraction anatomical changes between photon and proton dose distributions for children with abdominal tumors., Material and Methods: Volumetric modulated arc therapy (VMAT) and intensity-modulated pencil beam scanning (PBS) proton dose distributions were calculated for 20 abdominal pediatric cases (average 3, range 1-8 years). VMAT plans were based on a full-arc while PBS plans on 2-3 posterior-oblique irradiation fields. Plans were robustly optimized on a patient-specific internal target volume (ITV) using a uniform 5 mm set-up uncertainty. Additionally, for the PBS plans a ± 3% proton range uncertainty was accounted for. Fractional dose re-calculations were performed using the planning computed tomography (CT) deformably registered to the daily cone-beam CT (CBCT) images. Fractional doses were accumulated rigidly. Planned and CBCT accumulated VMAT and PBS dose distributions were compared using dose-volume histogram (DVH) parameters., Results: Significant better sparing of the organs at risk with a maximum reduction in the mean dose of 40% was achieved with PBS. Mean ITV DVH parameters differences between planned and CBCT accumulated dose distributions were smaller than 0.5% for both VMAT and PBS. However, the ITV coverage (V 95%  > 99%) was not reached for one patient for the accumulated VMAT dose distribution., Conclusions: For pediatric patients with abdominal tumors, improved dosimetric sparing was obtained with PBS compared to VMAT. In addition, PBS delivered by posterior-oblique irradiation fields demonstrated to be robust against anatomical inter-fraction changes. Compared to PBS, daily anatomical changes proved to affect the target coverage of VMAT dose distributions to a higher extent., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Purpose: The use of Stereotactic Body Radiotherapy (SBRT) for bone metastases is increasing rapidly. Therefore, knowledge of the inter-observer differences in tumor volume delineation is essential to guarantee precise dose delivery. The aim of this study is to compare inter-observer agreement in bone metastases delineated on different imaging modalities., Material and Methods: Twenty consecutive patients with bone metastases treated with SBRT were selected. All patients received CT and MR imaging in treatment position prior to SBRT. Five observers from three institutions independently delineated gross tumor volume (GTV) on CT alone, CT with co-registered MRI and MRI alone. Four contours per imaging modality per patient were available, as one set of contours was shared by 2 observers. Inter-observer agreement, expressed in generalized conformity index [CIgen], volumes of contours and contours center of mass (COM) were calculated per patient and imaging modality., Results: Mean GTV delineated on MR (45.9±52.0cm 3 ) was significantly larger compared to CT-MR (40.2±49.4cm 3 ) and CT (34.8±41.8cm 3 ). A considerable variation in CIgen was found on CT (mean 0.46, range 0.15-0.75) and CT-MRI (mean 0.54, range 0.17-0.71). The highest agreement was found on MRI (mean 0.56, range 0.20-0.77). The largest variations of COM were found in anterior-posterior direction for all imaging modalities., Conclusions: Large inter-observer variation in GTV delineation exists for CT, CT-MRI and MRI. MRI-based GTV delineation resulted in larger volumes and highest consistency between observers., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: The TRENDY trial is an international multi-center phase-II study, randomizing hepatocellular carcinoma (HCC) patients between transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) with a target dose of 48-54 Gy in six fractions. The radiotherapy quality assurance (QA) program, including prospective plan feedback based on automated treatment planning, is described and results are reported., Materials and Methods: Scans of a single patient were used as a benchmark case. Contours submitted by nine participating centers were compared with reference contours. The subsequent planning round was based on a single set of contours. A total of 20 plans from participating centers, including 12 from the benchmark case, 5 from a clinical pilot and 3 from the first study patients, were compared to automatically generated VMAT plans., Results: For the submitted liver contours, Dice Similarity Coefficients (DSC) with the reference delineation ranged from 0.925 to 0.954. For the GTV, the DSC varied between 0.721 and 0.876. For the 12 plans on the benchmark case, healthy liver normal-tissue complication probabilities (NTCPs) ranged from 0.2% to 22.2% with little correlation between NCTP and PTV-D95% (R 2  < 0.3). Four protocol deviations were detected in the set of 20 treatment plans. Comparison with co-planar autoVMAT QA plans revealed these were due to too high target dose and suboptimal planning. Overall, autoVMAT resulted in an average liver NTCP reduction of 2.2 percent point (range: 16.2 percent point to -1.8 percent point, p = 0.03), and lower doses to the healthy liver (p < 0.01) and gastrointestinal organs at risk (p < 0.001)., Conclusions: Delineation variation resulted in feedback to participating centers. Automated treatment planning can play an important role in clinical trials for prospective plan QA as suboptimal plans were detected., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: We aimed to investigate the suitability of treating patients with single brain metastases using stereotactic radiosurgery (SRS) with the MRL and to characterize the dosimetric impact at tissue-air interfaces resulting primarily from the electron return effect (ERE)., Material and Methods: 24 patients treated for intact single brain metastases were analyzed. Three radiotherapy plans with the same prescribed dose were generated for each case: (1) noncoplanar volumetric modulated arc therapy (VMAT), (2) coplanar step-and-shoot intensity modulated radiotherapy (IMRT) on the MRL in the absence (MRLB=0), and (3) in the presence of the transverse magnetic field (MRLB=1.5). The plans were evaluated using cumulative dose-volume histograms and by calculation of Paddick conformity index (CI), V100%, V12Gy minus gross tumor volume (V12Gy - GTV), and V2Gy. At tissue-air boundaries, the dosimetric impact of the magnetic field was quantified using a 5 mm rim of tissue., Results: All plans met the target coverage and organs-at-risk planning objectives. Differences between all investigated dosimetric parameters significantly favored the VMAT plans as compared to the MRLB=0 and MRLB=1.5 plans, except for V2Gy. The mean V12Gy - GTV and V2Gy marginally favored the MRLB=0 plans compared to the MRLB=1.5 plans (mean difference: 0.45 cm 3 , p = 0.0019 and 16.46 cm 3 , p < 0.0001, respectively). The presence of the magnetic field resulted in a statistically significant but small increase in mean dose and D 2cc in the skin (0.08 Gy, p < 0.0001 and 0.6 Gy, p < 0.0001, respectively) and around air cavities (0.07 Gy, p = 0.0092 and 0.3 Gy, p = 0.0004, respectively)., Conclusions: It is feasible to generate stereotactic radiation plans that satisfy clinical requirements using the MRL in the setting of single brain metastases. The dosimetric impact of the magnetic field including the ERE at tissue-air boundaries is minor and does not negatively impact target conformity or dose gradient., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: While surgery remains the cornerstone of rectal cancer treatment, organ-preservation is upcoming. Therefore, neo-adjuvant treatment should be optimized. By escalating doses, response can be increased. To limit toxicity of boost, accurate gross tumor volume (GTV) definition is required. MRI, especially undeformed fast spin echo diffusion-weighted MRI (DWI), looks promising for delineation. However, inconsistencies between observers should be quantified before clinical implementation. We aim to find which MRI sequence (T2w, DWI or combination) is optimal and clinically useful for GTV definition by evaluating inter-observer agreement., Methods: Locally advanced rectal cancer patients (tumors <10 cm from anal verge) were scanned on 3T MRI transverse T2w and DWI (b=800 s/mm(2)). Three independent observers delineated T2w, DWI and combination (Combi) after training-set. Volumes, conformity index (CI), and maximum Hausdorff distance (HD) were calculated between any observer-pair per patient per modality., Results: Twenty-four consecutive patients were included. One patient had cT2 (4.2%), 19 cT3 (79.1%) and 4 cT4 (16.7%), with 2 clinical node negative (8.3%), 4 cN1 (16.7%), and 18 cN2 (75.0%) on MRI. From 24 patients, 70 sequences were available (24x T2, 23x DWI, and 23x Combi). Between observers, no significant volume differences were observed per modality. T2 showed significantly largest volumes compared to DWI (mean difference 19.85 ml, SD 17.42, p<0.0001) and Combi (mean difference 7.16 ml, SD 11.58, p<0.0001). Mean CI was 0.70, 0.71 and 0.69 for T2, DWI and Combi respectively (p>0.61). Average HD was largest on T2 (18.60mm, max 31.40 mm, min 9.20mm)., Discussion: Delineation on DWI resulted in delineation of the smallest volumes with similar consistency and mean distances, but with slightly lower Hausdorff distances compared to T2 and Combi. However, with lack of a gold standard it remains difficult to establish if delineations also represent true tumor. Study strengths were DWI adaptation to exclude geometrical distortions and training-set. DWI shows great potential for delineation purposes as long as sufficient experience exists and geometrical distortions are eliminated., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: A methodology is presented to quantify the uncertainty associated with linear accelerator-based frameless intracranial stereotactic radiotherapy (SRT) combining end-to-end phantom tests and clinical data., Methods and Materials: The following steps of the SRT chain were analysed: planning computed tomography (CT) and magnetic resonance (MR) scans registration, target volume delineation, CT and cone beam CT (CBCT) registration and intrafraction-patient displacement. The overall accuracy was established with an end-to-end test. The measured uncertainties were combined, deriving the total systematic (ΣT) and random (σT) error components, to estimate the GTV-PTV margin., Results: The uncertainty in the MR-CT registration was on average 0.40mm (averaged over AP, CC and LR directions). Rotational variations were smaller than 0.5° in all directions. Interobser variation in GTV delineation was on average 0.29mm. The uncertainty in the CBCT-CT registration was on average 0.15mm. Again, rotational variations were smaller than 0.5° in all directions. The systematic and random intrafraction displacement errors were on average 0.55mm and 0.45mm, respectively. The systematic and random positional errors from the end-to-end test were on average 0.49mm and 0.53mm, respectively. Combining these uncertainties resulted in an average ΣT=0.9mm and σT=0.7mm and an average GTV-PTV margin of 2.8mm., Conclusion: This comprehensive methodology including end-to-end tests enabled a GTV-PTV margin calculation considering all sources of uncertainties. This generic method can also be used for other treatment sites., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)