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Purpose: Optic nerves are part of the craniospinal irradiation (CSI) target volume. Modern radiotherapy techniques achieve highly conformal target doses while avoiding organs-at-risk such as the lens. The magnitude of eye movement and its influence on CSI target- and avoidance volumes are unclear. We aimed to evaluate the movement-range of lenses and optic nerves and its influence on dose distribution of several planning techniques., Methods: Ten volunteers underwent MRI scans in various gaze directions (neutral, left, right, cranial, caudal). Lenses, orbital optic nerves, optic discs and CSI target volumes were delineated. 36-Gy cranial irradiation plans were constructed on synthetic CT images in neutral gaze, with Volumetric Modulated Arc Therapy, pencil-beam scanning proton therapy, and 3D-conventional photons. Movement-amplitudes of lenses and optic discs were analyzed, and influence of gaze direction on lens and orbital optic nerve dose distribution., Results: Mean eye structures' shift from neutral position was greatest in caudal gaze; -5.8±1.2 mm (±SD) for lenses and 7.0±2.0 mm for optic discs. In 3D-conventional plans, caudal gaze decreased Mean Lens Dose (MLD). In VMAT and proton plans, eye movements mainly increased MLD and diminished D98 orbital optic nerve (D98 OON ) coverage; mean MLD increased up to 5.5 Gy [total ΔMLD range -8.1 to 10.0 Gy], and mean D98 OON decreased up to 3.3 Gy [total ΔD98 OON range -13.6 to 1.2 Gy]. VMAT plans optimized for optic disc Internal Target Volume and lens Planning organ-at-Risk Volume resulted in higher MLD over gaze directions. D98 OON became ≥95% of prescribed dose over 95/100 evaluated gaze directions, while all-gaze bilateral D98 OON significantly changed in 1 of 10 volunteers., Conclusion: With modern CSI techniques, eye movements result in higher lens doses and a mean detriment for orbital optic nerve dose coverage of <10% of prescribed dose., Competing Interests: 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., (© 2021 The Author(s).)

Purpose: Numerous brain MR imaging studies have been performed to understand radiation-induced cognitive decline. However, many of them focus on a single region of interest, e.g. cerebral cortex or hippocampus. In this study, we use deformation-based morphometry (DBM) and voxel-based morphometry (VBM) to measure the morphological changes in patients receiving fractionated photon RT, and relate these to the dose. Additionally, we study tissue specific volume changes in white matter (WM), grey matter (GM), cerebrospinal fluid and total intracranial volume (TIV)., Methods and Materials: From our database, we selected 28 patients with MRI of high quality available at baseline and 1 year after RT. Scans were rigidly registered to each other, and to the planning CT and dose file. We used DBM to study non-tissue-specific volumetric changes, and VBM to study volume loss in grey matter. Observed changes were then related to the applied radiation dose (in EQD2). Additionally, brain tissue was segmented into WM, GM and cerebrospinal fluid, and changes in these volumes and TIV were tested., Results: Performing DBM resulted in clusters of dose-dependent volume loss 1 year after RT seen throughout the brain. Both WM and GM were affected; within the latter both cerebral cortex and subcortical nuclei show volume loss. Volume loss rates ranging from 5.3 to 15.3%/30 Gy were seen in the cerebral cortical regions in which more than 40% of voxels were affected. In VBM, similar loss rates were seen in the cortex and nuclei. The total volume of WM and GM significantly decreased with rates of 5.8% and 2.1%, while TIV remained unchanged as expected., Conclusions: Radiotherapy is associated with dose-dependent intracranial morphological changes throughout the entire brain. Therefore, we will consider to revise sparing of organs at risk based on future cognitive and neurofunctional data., Competing Interests: 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., (© 2021 The Author(s).)

Background and Purpose: Magnetic resonance guided radiotherapy (MRgRT) has been successfully implemented for several routine clinical applications in adult patients. The purpose of this study is to map the potential benefit of MRgRT on toxicity reduction and outcome in pediatric patients treated with curative intent for primary and metastatic sites., Materials and Methods: Between May and August 2020, a survey was distributed among SIOPE- and COG-affiliated radiotherapy departments, treating at least 25 pediatrics patients annually and being (candidate) users of a MRgRT system. The survey consisted of a table with 45 rows (clinical scenarios for primary (n = 28) and metastatic (n = 17) tumors) and 7 columns (toxicity reduction, outcome improvement, PTV margin reduction, target volume daily adaptation, online re-planning, intrafraction motion compensation and on-board functional imaging) and the option to answer by 'yes/no' . Afterwards, the Dutch national radiotherapy cohort was used to estimate the percentage of pediatric treatments that may benefit from MRgRT., Results: The survey was completed by 12/17 (71% response rate) institutions meeting the survey inclusion criteria. Responders indicated an 'expected benefit' from MRgRT for toxicity/outcome in 7% (for thoracic lymphomas and abdominal rhabdomyosarcomas)/0% and 18% (for mediastinal lymph nodes, lymph nodes located in the liver/splenic hilum, and liver metastases)/0% of the considered scenarios for the primary and metastatic tumor sites, respectively, and a 'possible benefit' was estimated in 64%/46% and 47%/59% of the scenarios. When translating the survey outcome into a clinical perspective a toxicity/outcome benefit, either expected or possible, was anticipated for 55%/24% of primary sites and 62%/38% of the metastatic sites., Conclusion: Although the benefit of MRgRT in pediatric radiation oncology is estimated to be modest, the potential role for reducing toxicity and improving clinical outcomes warrants further investigation. This fits best within the context of prospective studies or registration trials., Competing Interests: Dr. Hall reports an Honorarium from Accuray, Inc for Serving on the Scientific Review Committee, AERO 2019 Meeting. All other authors declared that there are no conflict of interest., (© 2021 The Author(s).)

Background: For decades, Anterior-Posterior/Posterior-Anterior (AP/PA) photon beams were standard-of-care for flank irradiation in children with renal cancer. Recently, highly conformal flank target volumes were defined correcting for postoperative organ shift and intra-fraction motion.By radiotherapy treatment plan comparison, this study aims to estimate the clinical benefits and potential risks of combining highly conformal target volumes with Volumetric-Modulated Arc Therapy (VMAT) versus conventional target volumes with AP/PA beams for flank irradiation., Materials and Methods: Twenty consecutive renal tumor cases (left/right-sided:10/10; median age:3.2 years) were selected. Highly conformal flank target volumes were generated for VMAT, while conventional target volumes were used for AP/PA. For each case, the dose to the organs at risk (OARs) and Total Body Volume (TBV) was calculated to compare VMAT with AP/PA treatment plans for a prescribed dose (PD) of 14.4/1.8 Gy. Dose constraint violation of the tail of the pancreas and spleen (D mean  < 10 Gy), heart (D 50  < 5 Gy) or mammary buds (D mean  < 10 Gy) were prioritized as potentially beneficial for clinics., Results: Highly conformal Planning Target Volumes (PTV) were smaller than conventional volumes (mean ΔPTV AP/PA -PTV VMAT : 555 mL, Δ60%, p=<0.01). A mean dose reduction favoring VMAT was observed for almost all OARs. Dose constraints to the tail of the pancreas, spleen, heart and mammary buds were fulfilled in 8/20, 12/20, 16/20 and 19/20 cases with AP/PA, versus 14/20, 17/20, 20/20 and 20/20 cases with VMAT, respectively. In 12/20 cases, VMAT prevented the dose constraint violation of one or more OARs otherwise exceeded by AP/PA. VMAT increased the TBV receiving 10% of the PD, but reduced the amount of irradiated TBV for all higher doses., Conclusion: Compared to 14.4 Gy flank irradiation using conventional AP/PA photon beams, an estimated clinical benefit by dose reduction to the OARs can be expected in 60% of the pediatric renal tumor cases using highly conformal flank target volumes combined with VMAT., Competing Interests: 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., (© 2021 The Author(s).)

Background and Purpose: Recently, the SIOP-RTSG developed a highly-conformal flank target volume definition for children with renal tumors. The aims of this study were to evaluate the inter-clinician delineation variation of this new target volume definition in an international multicenter setting and to explore the necessity of quality assurance., Materials and Methods: Six pediatric renal cancer cases were transferred to ten radiation oncologists from seven European countries ('participants'). These participants delineated the pre- and postoperative Gross Tumor Volume (GTV pre/post ), and Clinical Target Volume (CTV) during two test phases (case 1-2 and 3-4), followed by guideline refinement and a quality assurance phase (case 5-6). Reference target volumes (TV ref ) were established by three experienced radiation oncologists. The Dice Similarity Coefficient between the reference and participants (DSC ref/part ) was calculated per case. Delineations of case 5-6 were graded by four independent reviewers as 'per protocol' (0-4 mm), 'minor deviation' (5-9 mm) or 'major deviation' (≥10 mm) from the delineation guideline using 18 standardized criteria. Also, a major deviation resulting in underestimation of the CTV ref was regarded as an unacceptable variation., Results: A total of 57/60 delineation sets were completed. The median DSC ref/part for the CTV was 0.55 without improvement after sequential cases (case 3-4 vs. case 5-6: p = 0.15). For case 5-6, a major deviation was found for 5/18, 12/17, 18/18 and 4/9 collected delineations of the GTV pre , GTV post , CTV-T and CTV-N, respectively. An unacceptable variation from the CTV ref was found for 7/9 participants for case 5 and 6/9 participants for case 6., Conclusion: This international multicenter delineation exercise demonstrates that the new consensus for highly-conformal postoperative flank target volume delineation leads to geometrical variation among participants. Moreover, standardized review showed an unacceptable delineation variation in the majority of the participants. These findings strongly suggest the need for additional training and centralized pre-treatment review when this target volume delineation approach is implemented on a larger scale., Competing Interests: 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., (© 2021 The Author(s).)