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Current online adaptive radiotherapy (oART) workflows require dedicated equipment. Our aim was to develop and implement an oART workflow for a C-arm linac which can be performed using standard clinically available tools. A workflow was successfully developed and implemented. Three patients receiving palliative radiotherapy for bladder cancer were treated, with 33 of 35 total fractions being delivered with the cone-beam computed tomography (CBCT)-guided oART workflow. Average oART fraction duration was 24 min from start of CBCT acquisition to end of beam on. This work shows how oART could be performed without dedicated equipment, broadening oART availability for application at existing treatment machines., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Our department has a research agreement with Elekta AB on the development of adaptive strategies for the CBCT-linac. The first author is working on a grant for this purpose, which is partly financed by Elekta AB. Elekta AB had no role in the preparation, review, or approval of the manuscript and the decision to submit the manuscript., (© 2024 The Author(s).)

This work investigates the use of a multi-2D cine magnetic resonance imaging-based comprehensive motion monitoring (CMM) system for the assessment of prostate intrafraction 3D drifts. The data of six healthy volunteers were analyzed and the values of a clinically-relevant registration quality factor metric exported by CMM were presented. Additionally, the CMM-derived prostate motion was compared to a 3D-based reference and the 2D-3D tracking agreement was reported. Due to the low quality of SI motion tracking (often > 2 mm tracking mismatch between anatomical planes) we conclude that further improvements are desirable prior to clinical introduction of CMM for prostate drift corrections., 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., (© 2024 The Author(s).)

A subcommittee of the Netherlands Commission on Radiation Dosimetry (NCS) was initiated in 2018 with the task to update and extend a previous publication (NCS-15) on the quality assurance of treatment planning systems (TPS) (Bruinvis et al 2005). The field of treatment planning has changed considerably since 2005. Whereas the focus of the previous report was more on the technical aspects of the TPS, the scope of this report is broader with a focus on a department wide implementation of the TPS. New sections about education, automated planning, information technology (IT) and updates are therefore added. Although the scope is photon therapy, large parts of this report will also apply to all other treatment modalities. This paper is a condensed version of these guidelines; the full version of the report in English is freely available from the NCS website (http://radiationdosimetry.org/ncs/publications). The paper starts with the scope of this report in relation to earlier reports on this subject. Next, general aspects of the commissioning process are addressed, like e.g. project management, education, and safety. It then focusses more on technical aspects such as beam commissioning and patient modeling, dose representation, dose calculation and (automated) plan optimisation. The final chapters deal with IT-related subjects and scripting, and the process of updating or upgrading the TPS., (© 2023 Institute of Physics and Engineering in Medicine.)

Background Context: Palliative radiotherapy (RT) can lead to remineralization of osteolytic lesions thereby potentially restoring some of the weight-bearing capacity and preventing vertebral collapse. It is not clear, however, under which circumstances remineralization of osteolytic lesions occurs., Purpose: The aim of this study was to investigate the change in bone mineral density in spinal metastases after RT compared to a reference region, and find associated factors., Study Design: Retrospective analysis within prospective observational cohort OUTCOME MEASURES: change in bone mineral density measured in Hounsfield Units (HU)., Patient Sample: patients treated with RT for (painful) bone metastases., Methods: Patients with spinal metastases were included if computed tomography scans both pre- and post-RT were available. Bone density was measured in HU. A region of interest (ROI) was drawn manually in the metastatic lesion. As a reference, a measurement of bone density in adjacent, unaffected, and non-irradiated vertebrae was used. Factors tested for association were origin of the primary tumor, RT dose and fractionation scheme, and concomitant use of bisphosphonates., Results: A total of 31 patients with 49 spinal metastases, originating from various primary tumors, were included. The median age on baseline was 58 years (IQR: 53-63) and median time between baseline and follow-up scan was 8.2 months (IQR: 3.0-18.4). Difference in HU in the lesion before and after treatment was 146.9 HU (95% CI 68.4-225.4; p<.01). Difference in HU in the reference vertebra between baseline and first follow-up was 19.1 HU (95% CI -47.9 to 86.0; p=.58). Difference between reference vertebrae and metastatic lesions on baseline was -194.1 HU (95% CI -276.2 to -112.0; p<.01). After RT, this difference was reduced to -50.3 HU (95% CI -199.6 to 99.0; p=.52). Patients using bisphosphonates showed a greater increase in HU, 194.1 HU versus 60.6 HU, p=.01., Conclusions: Palliative radiation of osteolytic lytic spinal metastases is positively associated with an increased bone mineral density at follow-up. The use of bisphosphonates was linked to an increased bone mineral density when used during or after RT., 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 Inc. All rights reserved.)

In this work we present a framework for robust deep learning-based VMAT forward dose calculations for the 1.5T MR-linac. A convolutional neural network was trained on the dose of individual multi-leaf-collimator VMAT segments and was used to predict the dose per segment for a set of MR-linac-deliverable VMAT test plans. The training set consisted of prostate, rectal, lung and esophageal tumour data. All patients were previously treated in our clinic with VMAT on a conventional linac. The clinical data were converted to an MR-linac environment prior to training. During training time, gantry and collimator angles were randomized for each training sample, while the multi-leaf-collimator shapes were rigidly shifted to ensure robust learning. A Monte Carlo dose engine was used for the generation of the ground truth data at 1% statistical uncertainty per control point. For a set of 17 MR-linac-deliverable VMAT test plans, generated on a research treatment planning system, our method predicted highly accurate dose distributions, reporting 99.7% ± 0.5% for the full plan prediction at the 3%/3 mm gamma criterion. Additional evaluation on previously unseen IMRT patients passed all clinical requirements resulting in 99.0% ± 0.6% for the 3%/3 mm analysis. The overall performance of our method makes it a promising plan validation solution for IMRT and VMAT workflows, robust to tumour anatomies and tissue density variations., (Creative Commons Attribution license.)

Background: Intrafraction motion during radiotherapy limits margin reduction and dose escalation. Magnetic resonance (MR)-guided linear accelerators (MR-Linac) have emphasised this issue by enabling intrafraction imaging. We present and clinically apply a new workflow to counteract systematic intrafraction motion during MR-guided stereotactic body radiotherapy (SBRT)., Materials and Methods: With the sub-fractionation workflow, the daily dose is delivered in multiple sequential parts (sub-fractions), each adapted to the latest anatomy. As each sub-fractionation treatment plan complies with the dose constraints, no online dose accumulation is required. Imaging and treatment planning are executed in parallel with dose delivery to minimise dead time, enabling an efficient workflow. The workflow was implemented on a 1.5 T MR-Linac and applied in 15 prostate cancer (PCa) patients treated with 5 × 7.25 Gy in two sub-fractions of 3.625 Gy (10 × 3.625 Gy in total). Intrafraction clinical target volume (CTV) motion was determined and compared to a workflow with single-plan delivery. Furthermore, required planning target volume (PTV) margins were determined., Results: Average on-table time was 42.7 min. Except for two fractions, all fractions were delivered within 60 min. Average intrafraction 3D CTV displacement (±standard deviation) was 1.1 mm (± 0.7) with the sub-fractionation workflow, whereas this was up to 3.5 mm (± 2.4) without sub-fractionation. Calculated PTV margins required with sub-fractionation were 1.0 mm (left-right), 2.4 mm (cranial-caudal), and 2.6 mm (anterior-posterior)., Conclusion: Feasibility of the sub-fractionation workflow was demonstrated in 15 PCa patients treated with two sub-fractions on a 1.5 T MR-Linac. The workflow allows for significant PTV margin reduction in these patients by reducing systematic intrafraction motion during SBRT., 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 © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Magnetic resonance (MR)-linac delivery is expected to improve organ at risk (OAR) sparing. In this study, OAR doses were compared for online adaptive MR-linac treatments and conventional cone beam computed tomography (CBCT)-linac radiotherapy, taking into account differences in clinical workflows, especially longer session times for MR-linac delivery., Materials and Methods: For 25 patients with pelvic/abdominal lymph node oligometastases, OAR doses were calculated for clinical pre-treatment and daily optimized 1.5 T MR-linac treatment plans (5 × 7 Gy) and compared with simulated CBCT-linac plans for the pre-treatment and online anatomical situation. Bowelbag and duodenum were re-contoured on MR-imaging acquired before, during and after each treatment session. OAR hard constraint violations, D 0.5cc and D 10cc values were evaluated, focusing on bowelbag and duodenum., Results: Overall, hard constraints for all OAR were violated less often in daily online MR-linac treatment plans compared with CBCT-linac: in 5% versus 22% of fractions, respectively. D 0.5cc and D 10cc values did not differ significantly. When taking treatment duration and intrafraction motion into account, estimated delivered doses to bowelbag and duodenum were lower with CBCT-linac if identical planning target volume (PTV) margins were used for both modalities. When reduced PTV margins were achievable with MR-linac treatment, bowelbag doses were lower compared with CBCT-linac., Conclusions: Compared with CBCT-linac treatments, the online adaptive MR-linac approach resulted in fewer hard planning constraint violations compared with single-plan CBCT-linac delivery. With respect to other bowelbag/duodenum dose-volume parameters, the longer duration of MR-linac treatment sessions negatively impacts the potential dosimetric benefit of daily adaptive treatment planning., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The overarching University Medical Center Utrecht MR-linac scientific project, including employment of multiple authors, has been partly funded by Elekta AB (Stockholm, Sweden). Elekta did not have any part in the design, execution or analysis of this study. The authors declared that there is no other conflict of interest., (© 2022 The Authors. Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology.)

Background and purpose: Central lung tumours can be treated by magnetic resonance (MR)-guided radiotherapy. Complications might be reduced by decreasing the Planning Target Volume (PTV) using mid-position (midP)-based planning instead of Internal Target Volume (ITV)-based planning. In this study, we aimed to verify a method to automatically derive patient-specific PTV margins for midP-based planning, and show dosimetric robustness of midP-based planning for a 1.5T MR-linac. Materials and methods: Central(n = 12) and peripheral(n = 4) central lung tumour cases who received 8x7.5 Gy were included. A midP-image was reconstructed from ten phases of the 4D-Computed Tomography using deformable image registration. The Gross Tumor Volume (GTV) was delineated on the midP-image and the PTV margin was automatically calculated based on van Herk's margin recipe, treating the standard deviation of all Deformation Vector Fields, within the GTV, as random error component. Dosimetric robustness of midP-based planning for MR-linac using automatically derived margins was verified by 4D dose-accumulation. MidP-based plans were compared to ITV-based plans. Automatically derived margins were verified with manually derived margins. Results: The mean D95% target coverage in GTV + 2 mm was 59.9 Gy and 62.0 Gy for midP- and ITV-based central lung plans, respectively. The mean lung dose was significantly lower for midP-based treatment plans (difference:-0.3 Gy; p < 0.042 ). Automatically derived margins agreed within one millimeter with manually derived margins. Conclusions : This retrospective study indicates that mid-position-based treatment plans for central lung Stereotactic Body Radiation Therapy yield lower OAR doses compared to ITV-based treatment plans on the MR-linac. Patient-specific GTV-to-PTV margins can be derived automatically and result in clinically acceptable target coverage., 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., (© 2022 Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology.)

Background: Low skeletal muscle mass (SMM) is associated with adverse outcomes. SMM is often assessed at the third lumbar vertebra (L3) on abdominal imaging. Abdominal imaging is not routinely performed in patients with head and neck cancer (HNC). We aim to validate SMM measurement at the level of the third cervical vertebra (C3) on head and neck imaging., Material and Methods: Patients with pre-treatment whole-body computed tomography (CT) between 2010 and 2018 were included. Cross-sectional muscle area (CSMA) was manually delineated at the level of C3 and L3. Correlation coefficients and intraclass correlation coefficients (ICCs) were calculated. Cohen's kappa was used to assess the reliability of identifying a patient with low SMM., Results: Two hundred patients were included. Correlation between CSMA at the level of C3 and L3 was good (r = 0.75, p < 0.01). Using a multivariate formula to estimate CSMA at L3, including gender, age, and weight, correlation improved (r = 0.82, p < 0.01). The agreement between estimated and actual CSMA at L3 was good (ICC 0.78, p < 0.01). There was moderate agreement in the identification of patients with low SMM based on the estimated lumbar skeletal muscle mass index (LSMI) and actual LSMI (Cohen's κ: 0.57, 95%CI 0.45-0.69)., Conclusions: CSMA at C3 correlates well with CSMA at L3. There is moderate agreement in the identification of patients with low SMM based on the estimated lumbar SMI (based on measurement at C3) and actual LSMI., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Accelerated partial breast irradiation (APBI) may benefit from the MR-Linac for target definition, patient setup, and motion monitoring. In this planning study, we investigated whether prone or supine position is dosimetrically beneficial for APBI on an MR-Linac and we evaluated patient comfort., Materials and Methods: Twenty-patients (9 postoperative, 11 preoperative) with a DCIS or breast tumor <3 cm underwent 1.5 T MRI in prone and supine position. The tumor or tumor bed was delineated as GTV and a 2 cm CTV-margin and 0.5 cm PTV-margin were added. 1.5 T MR-Linac treatment plans (5 × 5.2 Gy) with 11 beams were created for both positions in each patient. We evaluated the number of plans that achieved the planning constraints and performed a dosimetric comparison between prone and supine position using the Wilcoxon signed-rank test (p-value <0.01 for significance). Patient experience during scanning was evaluated with a questionnaire., Results: All 40 plans met the target coverage and OAR constraints, regardless of position. Heart D mean was not significantly different (1.07 vs. 0.79 Gy, p-value: 0.027). V5Gy to the ipsilateral lung (4.4% vs. 9.8% median, p-value 0.009) and estimated delivery time (362 vs. 392 s, p-value: 0.003) were significantly lower for prone position. PTV coverage and dose to other OAR were comparable between positions. The majority of patients (13/20) preferred supine position., Conclusion: APBI on the MR-Linac is dosimetrically feasible in prone and supine position. Mean heart dose was similar in both positions. Ipsilateral lung V5Gy was lower in prone position., Competing Interests: Conflicts of interest The department of radiotherapy of the UMC Utrecht is part of the Elekta MR-Linac Research Consortium. Several authors have received financial support from Elekta for visiting consortium meetings. The funding sources had no role in the preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Whole bladder radiotherapy is challenging due to inter- and intrafraction size and shape changes. To account for these changes, currently a Library of Plans (LoP) technique is often applied, but daily adaptive radiotherapy is also increasingly becoming available. The aim of this study was to compare LoP with two magnetic resonance imaging guided radiotherapy (MRgRT) strategies by comparing target coverage and volume of healthy tissue inside the planning target volume (PTV) for whole bladder treatments., Methods and Materials: Data from 25 MRgRT lymph node oligometastases treatments (125 fractions) were used, with three MRI scans acquired at each fraction at 0, 15 and 30 min. Bladders were delineated and used to evaluate three strategies: 1) LoP with two plans for a 15 min fraction, 2) MRgRT 15min for a 15 min fraction and 3) MRgRT 30min for a 30 min fraction. The volumes of healthy tissue inside and bladder outside the PTV were analyzed on the simulated post-treatment images., Results: MRgRT 30min had 120% and 121% more healthy tissue inside the PTV than LoP and MRgRT 15min . For LoP slightly more target outside the PTV was found than for MRgRT 30min and MRgRT 15min , with median 0% (range 0-23%) compared to 0% (0-20%) and 0% (0-10%), respectively., Conclusions: Taking into account both target coverage and volume of healthy tissue inside the PTV, MRgRT 15min performed better than LoP and MRgRT 30min for whole bladder treatments. A 15 min daily adaptive radiotherapy workflow is needed to potentially benefit from replanning compared to LoP., 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 Authors.)

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).)

We present a robust deep learning-based framework for dose calculations of abdominal tumours in a 1.5 T MRI radiotherapy system. For a set of patient plans, a convolutional neural network is trained on the dose of individual multi-leaf-collimator segments following the DeepDose framework. It can then be used to predict the dose distribution per segment for a set of patient anatomies. The network was trained using data from three anatomical sites of the abdomen: prostate, rectal and oligometastatic tumours. A total of 216 patient fractions were used, previously treated in our clinic with fixed-beam IMRT using the Elekta MR-linac. For the purpose of training, 176 fractions were used with random gantry angles assigned to each segment, while 20 fractions were used for the validation of the network. The ground truth data were calculated with a Monte Carlo dose engine at 1% statistical uncertainty per segment. For a total of 20 independent abdominal test fractions with the clinical angles, the network was able to accurately predict the dose distributions, achieving 99.4% ± 0.6% for the whole plan prediction at the 3%/3 mm gamma test. The average dose difference and standard deviation per segment was 0.3% ± 0.7%. Additional dose prediction on one cervical and one pancreatic case yielded high dose agreement of 99.9% and 99.8% respectively for the 3%/3 mm criterion. Overall, we show that our deep learning-based dose engine calculates highly accurate dose distributions for a variety of abdominal tumour sites treated on the MR-linac, in terms of performance and generality.

Purpose: At our department, MR-guided stereotactic body radiation therapy (SBRT) using the 1.5T MR-linac system (Unity, Elekta AB, Stockholm, Sweden) has been initiated for patients with lymph node oligometastases. Superior soft tissue contrast and the possibility for online plan adaptation on the Unity may allow for hypofractionated treatment. The purpose of this study was to investigate the dosimetric feasibility and compare the plan quality of different hypofractionated schemes., Methods and Materials: Data was used from 12 patients with single lymph node oligometastases (10 pelvic, 2 para-aortic), which were all treated on the Unity with a prescribed dose of 5x7 Gy to 95% of the PTV. Hypofractionation was investigated for 3x10 Gy and 1x20 Gy schemes (all 60 Gy BED α/β = 10). The pre-treatment plans were evaluated based on dose criteria and plan quality. If all criteria were met, the number of online adapted plans which also met all dose criteria was investigated. For pre-treatment plans meeting the criteria for all three fractionation schemes, the plan quality after online adaptation was compared using the four parameters described in the NRG-BR001 phase 1 trial., Results: Pre-treatment plans met all clinical criteria for the three different fractionation schemes in 10, 9 and 6 cases. 50/50, 45/45 17/30 of the corresponding online adapted plans met all criteria, respectively. Violations were primarily caused by surrounding organs at risk overlapping or adjacent to the PTV. The 1x20 Gy treatment plans were, in general, of lesser quality than the 5x7 Gy and 3x10 Gy plans., Conclusion: Hypofractionated radiotherapy for lymph node oligometastases on the 1.5T MR-linac is feasible based on dose criteria and plan quality metrics. The location of the target relative to critical structures should be considered in choosing the most suitable fractionation scheme. Especially for single fraction treatment, meeting all dose criteria in the pre-treatment situation does not guarantee that this also applies during online treatment., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The University Medical Center Utrecht MR-linac scientific project, including employment of multiple authors, has been partly funded by Elekta AB (Stockholm, Sweden)., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Structure delineation is a necessary, yet time-consuming manual procedure in radiotherapy. Recently, convolutional neural networks have been proposed to speed-up and automatise this procedure, obtaining promising results. With the advent of magnetic resonance imaging (MRI)-guided radiotherapy, MR-based segmentation is becoming increasingly relevant. However, the majority of the studies investigated automatic contouring based on computed tomography (CT)., Purpose: In this study, we investigate the feasibility of clinical use of deep learning-based automatic OARs delineation on MRI., Materials and Methods: We included 150 patients diagnosed with prostate cancer who underwent MR-only radiotherapy. A three-dimensional (3D) T1-weighted dual spoiled gradient-recalled echo sequence was acquired with 3T MRI for the generation of the synthetic-CT. The first 48 patients were included in a feasibility study training two 3D convolutional networks called DeepMedic and dense V-net (dV-net) to segment bladder, rectum and femurs. A research version of an atlas-based software was considered for comparison. Dice similarity coefficient, 95% Hausdorff distances (HD 95 ), and mean distances were calculated against clinical delineations. For eight patients, an expert RTT scored the quality of the contouring for all the three methods. A choice among the three approaches was made, and the chosen approach was retrained on 97 patients and implemented for automatic use in the clinical workflow. For the successive 53 patients, Dice, HD 95 and mean distances were calculated against the clinically used delineations., Results: DeepMedic, dV-net and the atlas-based software generated contours in 60 s, 4 s and 10-15 min, respectively. Performances were higher for both the networks compared to the atlas-based software. The qualitative analysis demonstrated that delineation from DeepMedic required fewer adaptations, followed by dV-net and the atlas-based software. DeepMedic was clinically implemented. After retraining DeepMedic and testing on the successive patients, the performances slightly improved., Conclusion: High conformality for OARs delineation was achieved with two in-house trained networks, obtaining a significant speed-up of the delineation procedure. Comparison of different approaches has been performed leading to the succesful adoption of one of the neural networks, DeepMedic, in the clinical workflow. DeepMedic maintained in a clinical setting the accuracy obtained in the feasibility study.

Background and Purpose: Patients were treated at our institute for single and multiple lymph node oligometastases on the 1.5T MR-linac since August 2018. The superior soft-tissue contrast and additional software features of the MR-linac compared to CBCT-linacs allow for online adaptive treatment planning. The purpose of this study was to perform a target coverage and dose criteria based evaluation of the clinically delivered online adaptive radiotherapy treatment compared with conventional CBCT-linac treatment., Materials and Methods: Patient data was used from 14 patients with single lymph node oligometastases and 6 patients with multiple (2-3) metastases. All patients were treated on the 1.5T MR-linac with a prescribed dose of 5 × 7 Gy to 95% of the PTV and a CBCT-linac plan was created for each patient. The difference in target coverage between these plans was compared and plans were evaluated based on dose criteria for each fraction after calculating the CBCT-plan on the daily anatomy. The GTV coverage was evaluated based on the online planning and the post-delivery MRI., Results: For both single and multiple lymph node oligometastases the GTV V 35Gy had a median value of 100% for both the MR-linac plans and CBCT-plans pre- and post-delivery and did not significantly differ. The percentage of plans that met all dose constraints was improved from 19% to 84% and 20% to 67% for single and multiple lymph node cases, respectively., Conclusion: Target coverage and dose criteria based evaluation of the first clinical 1.5T MR-linac SBRT treatments of lymph node oligometastases compared with conventional CBCT-linac treatment shows a smaller amount of unplanned violations of high dose criteria. The GTV coverage was comparable. Benefit is primarily gained in patients treated for multiple lymph node oligometastases: geometrical deformations are accounted for, dose can be delivered in one plan and margins can be reduced., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

We present DeepDose, a deep learning framework for fast dose calculations in radiation therapy. Given a patient anatomy and linear-accelerator IMRT multi-leaf-collimator shape or segment, a novel set of physics-based inputs is calculated that encode the linac machine parameters into the underlying anatomy. These inputs are then used to train a deep convolutional network to derive the dose distribution of individual MLC shapes on a given patient anatomy. In this work we demonstrate the proof-of-concept application of DeepDose on 101 prostate patients treated in our clinic with fixed-beam IMRT. The ground-truth data used for training, validation and testing of the prediction were calculated with a state-of-the-art Monte Carlo dose engine at 1% statistical uncertainty per segment. A deep convolution network was trained using the data of 80 patients at the clinically used 3 mm 3 grid spacing while 10 patients were used for validation. For another 11 independent test patients, the network was able to accurately estimate the segment doses from the clinical plans of each patient passing the clinical QA when compared with the Monte Carlo calculations, yielding on average 99.9%±0.3% for the forward calculated patient plans at 3%/3 mm gamma tests. Dose prediction using the trained network was very fast at approximately 0.9 seconds for the input generation and 0.6 seconds for single GPU inference per segment and 1 minute per patient in total. The overall performance of this dose calculation framework in terms of both accuracy and inference speed, makes it compelling for online adaptive workflows where fast segment dose calculations are needed.

Introduction: An increasing number of patients is diagnosed with spinal metastases due to elevated cancer incidence and improved overall survival. Patients with symptomatic spinal bone metastases often receive radiotherapy with or without surgical stabilisation. Patients with a life expectancy of less than 3 months are generally deemed unfit for surgery, therefore adequate pre-treatment assessment of life expectancy is necessary. The aim of this study was to assess new factors associated with overall survival for this category of patients. Patients and methods: Patients who received radiotherapy for thoracic or lumbar spinal metastases from June 2013 to December 2016 were included in this study. The pre-treatment planning CT for radiotherapy treatment was used to assess the patient's visceral fat area, subcutaneous fat area, total muscle area and skeletal muscle density on a single transverse slice at the L3 level. The total muscle area was used to assess sarcopenia. Furthermore, data were collected on age, sex, primary tumour, Karnofsky performance score, medical history, number of bone metastases, non-bone metastases and neurological symptoms. Univariable and multivariable cox regressions were performed to determine the association between our variables of interest and the survival at 90 and 365 days. Results: A total of 310 patients was included. The median age was 67 years. Overall survival rates for 90 and 365 days were 71% and 36% respectively. For 90- and 365-day survival, the Karnofsky performance score, muscle density and primary tumour were independently significantly associated. The visceral or subcutaneous fat area and their ratio and sarcopenia were not independently associated with overall survival. Conclusions: Of the body morphology, only muscle density was statistically significant associated with overall survival after 90 and 365 days in patients with spinal bone metastases. Body fat distribution was not significantly associated with overall survival.

Online adaptive radiotherapy using the 1.5 Tesla MR-linac is feasible for SBRT (5 × 7 Gy) of pelvic lymph node oligometastases. The workflow allows full online planning based on daily anatomy. Session duration is less than 60 min. Quality assurance tests, including independent 3D dose calculations and film measurements were passed., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The promise of the MR-linac is that one can visualize all anatomical changes during the course of radiotherapy and hence adapt the treatment plan in order to always have the optimal treatment. Yet, there is a trade-off to be made between the time spent for adapting the treatment plan against the dosimetric gain. In this work, the various daily plan adaptation methods will be presented and applied on a variety of tumour sites. The aim is to provide an insight in the behavior of the state-of-the-art 1.5 T MRI guided on-line adaptive radiotherapy methods., Materials and Methods: To explore the different available plan adaptation workflows and methods, we have simulated online plan adaptation for five cases with varying levels of inter-fraction motion, regions of interest and target sizes: prostate, rectum, esophagus and lymph node oligometastases (single and multiple target). The plans were evaluated based on the clinical dose constraints and the optimization time was measured., Results: The time needed for plan adaptation ranged between 17 and 485 s. More advanced plan adaptation methods generally resulted in more plans that met the clinical dose criteria. Violations were often caused by insufficient PTV coverage or, for the multiple lymph node case, a too high dose to OAR in the vicinity of the PTV. With full online replanning it was possible to create plans that met all clinical dose constraints for all cases., Conclusion: Daily full online replanning is the most robust adaptive planning method for Unity. It is feasible for specific sites in clinically acceptable times. Faster methods are available, but before applying these, the specific use cases should be explored dosimetrically.

Objectives: Skeletal muscle mass (SMM) is most often assessed in cancer patients on abdominal computed tomography (CT) imaging at the level of the third lumbar vertebra (L3). Abdominal CT imaging is not routinely performed in head and neck cancer (HNC) patients. Recently, a novel method to assess SMM on a single transversal CT slice at the level of the third cervical vertebra (C3) was published. The objective of this study was to assess the robustness of this novel C3 measurement method in terms of interobserver agreement., Patients and Methods: Patients diagnosed with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) at our center between 2007 and 2011 were evaluated. Fifty-four patients with were randomly selected for analysis. Six observers independently measured the cross-sectional muscle area (CSMA) at the level of C3 using a predefined, written protocol as instruction. Interobserver agreement was assessed using intraclass correlation coefficients (ICCs), a Bland-Altman plot and Fleiss' kappa (κ)., Results: The agreement in vertebra selection between all observers was excellent (Fleiss' κ: 0.96). There was a substantial agreement between all observers in single slice selection (Fleiss' κ: 0.61). For all CSMA measurements, ICCs were excellent (0.763-0.969; all p < 0.001). The Bland-Altman plot showed good agreement between measurements, with narrow limits of agreement., Conclusion: Interobserver agreement for SMM measurement at the level of C3 was excellent. Assessment of SMM at the level of C3 is easy and robust and can performed on routinely available imaging in HNC patients.

Background and Purpose: With magnetic resonance imaging (MRI)-guided radiotherapy systems such as the 1.5T MR-linac the daily anatomy can be visualized before, during and after radiation delivery. With these treatment systems, seeing metastatic nodes with MRI and zapping them with stereotactic body radiotherapy (SBRT) comes into reach. The purpose of this study is to investigate different online treatment planning strategies and to determine the planning target volume (PTV) margin needed for adequate target coverage when treating lymph node oligometastases with SBRT on the 1.5T MR-linac., Materials and Methods: Ten patients were treated for single pelvic or para-aortic lymph node metastases on the 1.5T MR-linac with a prescribed dose of 5x7Gy with a 3 mm isotropic GTV- PTV margin. Based on the daily MRI and actual contours, a completely new treatment plan was generated for each session (adapt to shape, ATS). These were compared with plans optimized on pre-treatment CT contours after correcting for the online target position (adapt to position, ATP). At the end of each treatment session, a post-radiation delivery MRI was acquired on which the GTV was delineated to evaluate the GTV coverage and PTV margins., Results: The median PTV V 35Gy was 99.9% [90.7-100%] for the clinically delivered ATS plans compared to 93.6% [76.3-99.7%] when using ATP. The median GTV V 35Gy during radiotherapy delivery was 100% [98-100%] on the online planning and post-delivery MRIs for ATS and 100% [93.9-100%] for ATP, respectively. The applied 3 mm isotropic PTV margin is considered adequate., Conclusion: For pelvic and para-aortic metastatic lymph nodes, online MRI-guided adaptive treatment planning results in adequate PTV and GTV coverage when taking the actual patient anatomy into account (ATS). Generally, GTV coverage remained adequate throughout the treatment session for both adaptive planning strategies. "Seeing and zapping" metastatic lymph nodes comes within reach for MRI-guided SBRT.

Background and Purpose: Recent studies have shown that the use of magnetic resonance (MR) guided online plan adaptation yields beneficial dosimetric values and reduces unplanned violations of the dose constraints for stereotactic body radiation therapy (SBRT) of lymph node oligometastases. The purpose of this R-IDEAL stage 0 study was to determine the optimal plan adaptation approach for MR-guided SBRT treatment of lymph node oligometastases., Materials and Methods: Using pre-treatment computed tomography (CT) and repeated MR data from five patients with in total 17 pathological lymph nodes, six different methods of plan adaptation were performed on the daily MRI and contours. To determine the optimal plan adaptation approach for treatment of lymph node oligometastases, the adapted plans were evaluated using clinical dose criteria and the time required for performing the plan adaptation., Results: The average time needed for the different plan adaptation methods ranged between 11 and 119 s. More advanced adaptation methods resulted in more plans that met the clinical dose criteria [range, 0-16 out of 17 plans]. The results show a large difference between target coverage achieved by the different plan adaptation methods., Conclusion: Results suggested that multiple plan adaptation methods, based on plan adaptation on the daily anatomy, were feasible for MR-guided SBRT treatment of lymph node oligometastases. The most advanced method, in which a full online replanning was performed by segment shape and weight optimization after fluence optimization, yielded the most favourable dosimetric values and could be performed within a time-frame acceptable (<5 min) for MR-guided treatment., (© 2019 The Authors.)

Purpose: Online 1.5T MR imaging on the MR-linac gives better target visualization compared to CBCT and facilitates online adaptive treatment strategies including daily replanning. In this simulation study, the dosimetric impact of online replanning was investigated for SBRT of lymph node oligometastases as a method for correcting for inter-fraction anatomical changes., Methods: Pre-treatment plans were created for 17 pelvic and para-aortic lymph nodes, with 3 and 8 mm PTV margins reflecting our clinical practice for lymph nodes with good and poor visibility on CBCT. The dose-volume parameters of the pre-treatment plans were evaluated on daily anatomy as visible on the repeated MRIs and compared to online replanning., Results: With online MRI-based replanning significant dosimetric improvements are obtained for the rectum, bladder, bowel and sigmoid without compromising the target dose. The amount of unintended violations of the dose constraints for target and surrounding organs could be reduced by 75% for 8 mm and 66% for 3 mm PTV margins., Conclusion: The use of online replanning based on the actual anatomy as seen on repeated MRI compared to online position correction for lymph node oligometastases SBRT gives beneficial dosimetric outcomes and reduces the amount of unplanned violations of dose constraints.

The superior soft tissue contrast provided by magnetic resonance (MR) images on the 1.5T MR-linac allows for the incorporation of patient anatomy information. In this retrospective case study, we present the simulated dosimetric effects and timings of full online replanning as compared to the five plan adaptation methods currently available on the 1.5T MR-linac treatment system. For this case, it is possible to create treatment plans with all six methods within a time slot suitable for an online treatment procedure. However, large dosimetric differences between the plan adaptation methods and full online replanning are present with regards to target coverage and dose to organs at risk (OARs)., Competing Interests: The authors have declared that no competing interests exist.

The integration of 1.5 T MRI functionality with a radiotherapy linear accelerator (linac) has been pursued since 1999 by the UMC Utrecht in close collaboration with Elekta and Philips. The idea behind this integrated device is to offer unrivalled, online and real-time, soft-tissue visualization of the tumour and the surroundings for more precise radiation delivery. The proof of concept of this device was given in 2009 by demonstrating simultaneous irradiation and MR imaging on phantoms, since then the device has been further developed and commercialized by Elekta. The aim of this work is to demonstrate the clinical feasibility of online, high-precision, high-field MRI guidance of radiotherapy using the first clinical prototype MRI-Linac. Four patients with lumbar spine bone metastases were treated with a 3 or 5 beam step-and-shoot IMRT plan. The IMRT plan was created while the patient was on the treatment table and based on the online 1.5 T MR images; pre-treatment CT was deformably registered to the online MRI to obtain Hounsfield values. Bone metastases were chosen as the first site as these tumors can be clearly visualized on MRI and the surrounding spine bone can be detected on the integrated portal imager. This way the portal images served as an independent verification of the MRI based guidance to quantify the geometric precision of radiation delivery. Dosimetric accuracy was assessed post-treatment from phantom measurements with an ionization chamber and film. Absolute doses were found to be highly accurate, with deviations ranging from 0.0% to 1.7% in the isocenter. The geometrical, MRI based targeting as confirmed using portal images was better than 0.5 mm, ranging from 0.2 mm to 0.4 mm. In conclusion, high precision, high-field, 1.5 T MRI guided radiotherapy is clinically feasible.

Purpose: To enable fast online replanning for prostate radiotherapy with the inclusion of interfraction rotations and translations and investigate the possibility for margin reduction via this regime., Methods: Online daily replanning for a 35-fraction treatment for five prostate cases is simulated while accounting for anatomical transformations derived from fiducial marker data available in our clinic. Two online replanning strategies were simulated, compensating for: (a) rotation-only in combination with a couch shift and (b) both translation and rotation without a couch shift. They were compared against our current clinical protocol consisting of a single offline plan used over all fractions with daily couch repositioning (translations only). For every patient, the above methods were generated for several planning margins (0-8 mm with 2 mm increments) in order to assess the performance of online replanning in terms of target coverage and investigate the possible dosimetric benefit for the organs at risk. The daily DVHs for each treatment strategy were used for evaluation and the non tumor integral dose (NTID) for the different margins was calculated in order to quantify the overall reduction of the delivered energy to the patient., Results: Our system is able to generate a daily automated prostate plan in less than 2 min. For every patient, the daily treatment plans produce similar dose distributions to the original approved plan (average CTV D99 relative difference: 0.2%). The inclusion of both shifts and rotations can be effectively compensated via replanning among all planning margins (average CTV D99 difference: 0.01 Gy between the two replanning regimes). Online replanning is able to maintain target coverage among all margins, while - as expected - the conventional treatment plan is increasingly affected by the interfraction rotations as the margins shrink (average CTV D99 decrease: 0.2 Gy at 8 mm to 2.9 Gy at 0 mm margin). The possible gain in total delivered energy to the patient was quantified by the decreased NTID ranging from 12.6% at 6 mm to 32.9% at 0 mm., Conclusions: We demonstrate that fast daily replanning can be utilized to account for daily rotations and translations based on the daily positioning protocol. A daily plan can be generated from scratch in less than 2 min making it suitable for online application. Given the large magnitude of prostate rotation around the LR axis, online correction for daily rotations can be beneficial even for the clinical 8 mm margin and could be utilized for treatments with small margin reduction mainly limited then by anatomical deformations and intrafraction motion. Our online replanning pipeline can be used in future treatments with online MR guidance that can lead to further safe reduction of the planning margins., (© 2017 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

The hybrid MRI-radiotherapy machines, like the MR-linac (Elekta AB, Stockholm, Sweden) installed at the UMC Utrecht (Utrecht, The Netherlands), will be able to provide real-time patient imaging during treatment. In order to take advantage of the system's capabilities and enable online adaptive treatments, a new generation of software should be developed, ranging from motion estimation to treatment plan adaptation. In this work we present a proof of principle adaptive pipeline designed for high precision stereotactic body radiation therapy (SBRT) suitable for sites affected by respiratory motion, like renal cell carcinoma (RCC). We utilized our research MRL treatment planning system (MRLTP) to simulate a single fraction 25 Gy free-breathing SBRT treatment for RCC by performing inter-beam replanning for two patients and one volunteer. The simulated pipeline included a combination of (pre-beam) 4D-MRI and (online) 2D cine-MR acquisitions. The 4DMRI was used to generate the mid-position reference volume, while the cine-MRI, via an in-house motion model, provided three-dimensional (3D) deformable vector fields (DVFs) describing the anatomical changes during treatment. During the treatment fraction, at an inter-beam interval, the mid-position volume of the patient was updated and the delivered dose was accurately reconstructed on the underlying motion calculated by the model. Fast online replanning, targeting the latest anatomy and incorporating the previously delivered dose was then simulated with MRLTP. The adaptive treatment was compared to a conventional mid-position SBRT plan with a 3 mm planning target volume margin reconstructed on the same motion trace. We demonstrate that our system produced tighter dose distributions and thus spared the healthy tissue, while delivering more dose to the target. The pipeline was able to account for baseline variations/drifts that occurred during treatment ensuring target coverage at the end of the treatment fraction.

To develop an automated radiotherapy treatment planning and optimization workflow to efficiently create patient specifically optimized clinical grade treatment plans for prostate cancer and to implement it in clinical practice. A two-phased planning and optimization workflow was developed to automatically generate 77Gy 5-field simultaneously integrated boost intensity modulated radiation therapy (SIB-IMRT) plans for prostate cancer treatment. A retrospective planning study (n  =  100) was performed in which automatically and manually generated treatment plans were compared. A clinical pilot (n  =  21) was performed to investigate the usability of our method. Operator time for the planning process was reduced to  <5 min. The retrospective planning study showed that 98 plans met all clinical constraints. Significant improvements were made in the volume receiving 72Gy (V72Gy) for the bladder and rectum and the mean dose of the bladder and the body. A reduced plan variance was observed. During the clinical pilot 20 automatically generated plans met all constraints and 17 plans were selected for treatment. The automated radiotherapy treatment planning and optimization workflow is capable of efficiently generating patient specifically optimized and improved clinical grade plans. It has now been adopted as the current standard workflow in our clinic to generate treatment plans for prostate cancer.

Conventional treatment planning in intensity-modulated radiation therapy (IMRT) is a trial-and-error process that usually involves tedious tweaking of optimization parameters. Here, we present an algorithm that automates part of this process, in particular the adaptation of voxel-based penalties within normal tissue. Thereby, the proposed algorithm explicitly considers a priori known physical limitations of photon irradiation. The efficacy of the developed algorithm is assessed during treatment planning studies comprising 16 prostate and 5 head and neck cases. We study the eradication of hot spots in the normal tissue, effects on target coverage and target conformity, as well as selected dose volume points for organs at risk. The potential of the proposed method to generate class solutions for the two indications is investigated. Run-times of the algorithms are reported. Physically constrained voxel-based penalty adaptation is an adequate means to automatically detect and eradicate hot-spots during IMRT planning while maintaining target coverage and conformity. Negative effects on organs at risk are comparably small and restricted to lower doses. Using physically constrained voxel-based penalty adaptation, it was possible to improve the generation of class solutions for both indications. Considering the reported run-times of less than 20 s, physically constrained voxel-based penalty adaptation has the potential to reduce the clinical workload during planning and automated treatment plan generation in the long run, facilitating adaptive radiation treatments., (© 2016 The Authors)

The new era of hybrid MRI and linear accelerator machines, including the MR-linac currently being installed in the University Medical Center Utrecht (Utrecht, The Netherlands), will be able to provide the actual anatomy and real-time anatomy changes of the patient's target(s) and organ(s) at risk (OARs) during radiation delivery. In order to be able to take advantage of this input, a new generation of treatment planning systems is needed, that will allow plan adaptation to the latest anatomy state in an online regime. In this paper, we present a treatment planning algorithm for intensity-modulated radiotherapy (IMRT), which is able to compensate for patient anatomy changes. The system consists of an iterative sequencing loop open to anatomy updates and an inter- and intrafraction adaptation scheme that enables convergence to the ideal dose distribution without the need of a final segment weight optimization (SWO). The ability of the system to take into account organ motion and adapt the plan to the latest anatomy state is illustrated using artificial baseline shifts created for three different kidney cases. Firstly, for two kidney cases of different target volumes, we show that the system can account for intrafraction motion, delivering the intended dose to the target with minimal dose deposition to the surroundings compared to conventional plans. Secondly, for a third kidney case we show that our algorithm combined with the interfraction scheme can be used to deliver the prescribed dose while adapting to the changing anatomy during multi-fraction treatments without performing a final SWO.

Proton therapy promises higher dose conformality in comparison with regular radiotherapy techniques. Also, image guidance has an increasing role in radiotherapy and MRI is a prime candidate for this imaging. Therefore, in this paper the dosimetric feasibility of Intensity Modulated Proton Therapy (IMPT) in a magnetic field of 1.5 T and the effect on the generated dose distributions compared to those at 0 T is evaluated, using the Monte Carlo software TOol for PArticle Simulation (TOPAS). For three different anatomic sites IMPT plans are generated. It is shown that the generation of an IMPT plan in a magnetic field is feasible, the impact of the magnetic field is small, and the resulting dose distributions are equivalent for 0 T and 1.5 T. Also, the framework of Monte Carlo simulation combined with an inverse optimization method can be used to generate IMPT plans. These plans can be used in future dosimetric comparisons with e.g. IMRT and conventional IMPT. Finally, this study shows that IMPT in a 1.5 T magnetic field is dosimetrically feasible.

Unlabelled: Before (166)Ho radioembolization, a small batch of the same type of microspheres is administered as a scout dose instead of the conventional (99m)Tc-macroaggregated albumin ((99m)Tc-MAA). The (166)Ho scout dose provides a more accurate and precise lung shunt assessment. However, in contrast to (99m)Tc-MAA, an unintended extrahepatic deposition of this β-emitting scout dose could inflict radiation damage, the extent of which we aimed to quantify in this study., Methods: All patients eligible for radioembolization in our institute between January 2011 and March 2014 were reviewed. Of the extrahepatic depositions of (99m)Tc-MAA on SPECT, the amount and volume were measured. These were used to calculate the theoretic absorbed dose in the case a (166)Ho scout dose had been used. The extrahepatic activity was measured as the sum of all voxels of the deposition. Volumes were measured using a threshold technique including all voxels from the maximum voxel intensity up to a certain percentage. The threshold needed to obtain the true volume was studied in a phantom study., Results: In the phantom study, a threshold of 40% was found to overestimate the volume, with the consequence of underestimating the absorbed dose. Of 160 patients, 32 patients (34 cases) of extrahepatic deposition were identified. The depositions contained a median of 1.3% (range, 0.1%-19.5%) of the administered activity in a median volume of 6.8 mL (range, 1.1-42 mL). The use of a scout dose of 250 MBq of (166)Ho microspheres in these cases would theoretically have resulted in a median absorbed dose of 6.0 Gy (range, 0.9-374 Gy). The dose exceeded a limit of 49 Gy (reported in 2013) in 2 of 34 cases (5.9%; 95% confidence interval, 0.7%-20.1%) or 2 of 160 (1.3%; 95% confidence interval, 0.1%-4.7%) of all patients. In these 2 patients with a large absorbed dose (112 and 374 Gy), the culprit vessel was identified in 1 case., Conclusion: Extrahepatic deposition of a (166)Ho scout dose seems to be theoretically safe in most patients. Its safety in clinical practice is being evaluated in ongoing clinical trials., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

The MRI linear accelerator (MR-linac) that is currently being installed in the University Medical Center Utrecht (Utrecht, The Netherlands), will be able to track the patient's target(s) and Organ(s) At Risk during radiation delivery. In this paper, we present a treatment planning system for intensity-modulated radiotherapy (IMRT). It is capable of Adaptive Radiotherapy and consists of a GPU Monte Carlo dose engine, an inverse dose optimization algorithm and a novel adaptive sequencing algorithm. The system is able to compensate for patient anatomy changes and enables radiation delivery immediately from the first calculated segment. IMRT plans meeting all clinical constraints were generated for two breast cases, one spinal bone metastasis case, two prostate cases with integrated boost regions and one head and neck case. These plans were generated by the segment weighted version of our algorithm, in a 0 T environment in order to test the feasibility of the new sequencing strategy in current clinical conditions, yielding very small differences between the fluence and sequenced distributions. All plans went through stringent experimental quality assurance on Delta4 and passed all clinical tests currently performed in our institute. A new inter-fraction adaptation scheme built on top of this algorithm is also proposed that enables convergence to the ideal dose distribution without the need of a final segment weight optimization. The first results of this method confirm that convergence is achieved within the first fractions of the treatment. These features combined will lead to a fully adaptive intra-fraction planning system able to take into account patient anatomy updates during treatment.

With the development of the 1.5 T MRI linear accelerator and the clinical introduction of the 0.35 T ViewRay™ system, delivering intensity-modulated radiotherapy (IMRT) in a transverse magnetic field becomes increasingly important. When delivering dose in the presence of a transverse magnetic field, one of the most prominent phenomena occurs around air cavities: the electron return effect (ERE). For stationary, spherical air cavities which are centrally located in the phantom, the ERE can be compensated by using opposing beams configurations in combination with IMRT. In this paper we investigate the effects of non-stationary spherical air cavities, centrally located within the target in a phantom containing no organs at risk, on IMRT dose delivery in 0.35 T and 1.5 T transverse magnetic fields by using Monte Carlo simulations. We show that IMRT can be used for compensating ERE around those air cavities, except for intrafraction appearing or disappearing air cavities. For these cases, gating or plan re-optimization should be used. We also analyzed the option of using IMRT plans optimized at 0 T to be delivered in the presence of 0.35 T and 1.5 T magnetic field. When delivering dose at 0.35 T, IMRT plans optimized at 0 T and 0.35 T perform equally well regarding ERE compensation. Within a 1.5 T environment, the 1.5 T optimized plans perform slightly better for the static and random intra- and interfraction air cavity movement cases than the 0 T optimized plans. For non-stationary spherical air cavities with a baseline shift (intra- and interfraction) the 0 T optimized plans perform better. These observations show the intrinsic ERE compensation by equidistant and opposing beam configurations for spherical air cavities within the target area. IMRT gives some additional compensation, but only in case of correct positioning of the air cavity according to the IMRT compensation. For intrafraction appearing or disappearing air cavities this correct positioning is absent and gating or plan re-optimization should be used.

Background and Purpose: To evaluate volume changes and position shifts and their contribution to treatment margins of pelvic and para-aortic lymph nodes during Intensity Modulated Radiation Therapy (IMRT) for advanced cervical cancer., Materials and Methods: Seventeen patients with visible nodes on MR images underwent T2-weighted MR scans before and weekly during the course of IMRT. Thirty-nine pelvic and para-aortic nodes were delineated on all scans. Margins accommodating for volume and position changes were taken from the boundaries of the nodal volumes in the six main directions., Results: Nodal volume regression from the pre-treatment situation to week 4 was 58% on average (range: 11.7% increase to 100% decrease). Nodal volumes partly increased between the pre-treatment scans and the scans in weeks 1-3, but in week 4 all nodes except one had regressed. Around the nodal volumes manually derived ITV margins accounting for volume changes and position shifts of 7.0, 4.0, 7.0, 8.0, 7.0 and 9.0mm to the medial, lateral, anterior, posterior, superior and inferior directions were needed to cover 95% of all nodes., Conclusions: We used weekly MR scans to derive inhomogeneous margins that accommodate for nodal volume and position changes during treatment. These margins should be taken into consideration when planning external beam radiotherapy (EBRT) boosts, especially for highly conformal boosting techniques., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

When delivering conventional intensity modulated radiotherapy (IMRT), discrepancies between the pre-treatment CT/MRI/PET based patient geometry and the daily patient geometry are minimized by performing couch translations and/or small rotations. However, full compensation of, in particular, rotations is usually not possible. In this paper, we introduce an online 'virtual couch shift (VCS)': we translate and/or rotate the pre-treatment dose distribution to compensate for the changes in patient anatomy and generate a new plan which delivers the transformed dose distribution automatically. We show for a phantom and a cervical cancer patient case that VCS accounts for both translations and large rotations equally well in terms of DVH results and 2%/2 mm γ analyses and when the various aspects of the clinical workflow can be implemented successfully, VCS can potentially outperform physical couch translations and/or rotations. This work is performed in the context of our hybrid 1.5 T MRI linear accelerator, which can provide translations and rotations but also deformations of the anatomy. The VCS is the first step toward compensating all of these anatomical changes by online re-optimization of the IMRT dose distribution.

The MRI accelerator, a combination of a 6 MV linear accelerator with a 1.5 T MRI, facilitates continuous patient anatomy updates regarding translations, rotations and deformations of targets and organs at risk. Accounting for these demands high speed, online intensity-modulated radiotherapy (IMRT) re-optimization. In this paper, a fast IMRT optimization system is described which combines a GPU-based Monte Carlo dose calculation engine for online beamlet generation and a fast inverse dose optimization algorithm. Tightly conformal IMRT plans are generated for four phantom cases and two clinical cases (cervix and kidney) in the presence of the magnetic fields of 0 and 1.5 T. We show that for the presented cases the beamlet generation and optimization routines are fast enough for online IMRT planning. Furthermore, there is no influence of the magnetic field on plan quality and complexity, and equal optimization constraints at 0 and 1.5 T lead to almost identical dose distributions.

Study Type: Prognostic (case series)., Level of Evidence: 4. What's known on the subject? and What does the study add? Nowadays more and more publications have been published about the topic prostate cancer aggressiveness and obesity with mixed results. However, most of the publications used the BMI as a marker for obesity, while the most metabolic active fat is the visceral fat. To learn more about these relations we measured and used the visceral fat in our paper., Objective: To examine if the periprostatic fat measured on computed tomography (CT) correlates with advanced disease we examined patients who received radiotherapy for localized prostate cancer. Several USA reports found a positive association between obesity and prostate cancer aggressiveness. However, in recent European studies these conclusions were not confirmed. Studies concerning this issue have basically relied on body mass index (BMI), as a marker of general obesity. Visceral fat, however, is the most metabolically active and best measured on CT., Patients and Methods: In 932 patients, who were treated with external radiotherapy (N=311) or brachytherapy (N=621) for their T1-3N0M0 prostate cancer, different fat measurements (periprostatic fat, subcutaneous fat thickness) were performed on a CT. Associations between the different fat measurements and risk of having high-risk (according to Ash et al., PSA>20 or Gleason score≥8 or T3) disease was measured., Results: The median age (IQR) was 67.0 years (62.0-71.0) and median BMI (IQR) was 25.8 (24.2-28.3). Logistic regression analyses, adjusted for age, revealed a significant association between periprostatic fat density (PFD) and risk of having a high risk disease. (Odds ratio [95% CI] 1.06 [1.04-1.08], P<0.001), Conclusion: Patients with a higher PFD had more often aggressive prostate cancer., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: Several reports found that obesity was associated with prostate cancer (PC) aggressiveness among men treated with radical prostatectomy or radiotherapy. Studies concerning this issue have basically relied on body mass index (BMI), as a marker for general obesity. Because visceral fat is the most metabolic active fat, we sought to evaluate if periprostatic fat measured on a computed tomography (CT) is a better marker than BMI to predict PC aggressiveness in a Dutch population who underwent brachytherapy for localized PC., Patients and Methods: Of the 902 patients who underwent brachytherapy, 725 CT scans were available. Subcutaneous fat thickness (CFT), periprostatic fat area (cm(2)) and fat-density (%) were determined on the CT scan. Patients were stratified into three groups: <25, 25-75 and >75 percentile of the fat-density. Associations between the three fat-density subgroups and BMI and PC aggressiveness were examined., Results: 237 patients were classified as having normal weight (37.2%), 320 as overweight (50.2%) and 80 as obese (12.6%). There was a strong significant association between BMI and fat-density and CFT. The strongest correlation was seen between BMI and CFT (Pearson r coefficient = 0.71). Logistic regression analysis revealed no statistically significant association between the different fat measurements and the risk of having a high-risk disease., Conclusions: Periprostatic fat and fat-density as measured with CT were not correlated with PC aggressiveness in patients receiving brachytherapy. However, 31% of the patients with a normal BMI had a fat-density of >75 percentile of the periprostatic fat-density.