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Objective. This study aims to develop and evaluate a fast and robust deep learning-based auto-segmentation approach for organs at risk in MRI-guided radiotherapy of pancreatic cancer to overcome the problems of time-intensive manual contouring in online adaptive workflows. The research focuses on implementing novel data augmentation techniques to address the challenges posed by limited datasets. Approach. This study was conducted in two phases. In phase I, we selected and customized the best-performing segmentation model among ResU-Net, SegResNet, and nnU-Net, using 43 balanced 3DVane images from 10 patients with 5-fold cross-validation. Phase II focused on optimizing the chosen model through two advanced data augmentation approaches to improve performance and generalizability by increasing the effective input dataset: (1) a novel structure-guided deformation-based augmentation approach (sgDefAug) and (2) a generative adversarial network-based method using a cycleGAN (GANAug). These were compared with comprehensive conventional augmentations (ConvAug). The approaches were evaluated using geometric (Dice score, average surface distance (ASD)) and dosimetric (D2% and D50% from dose-volume histograms) criteria. Main results. The nnU-Net framework demonstrated superior performance (mean Dice: 0.78 ± 0.10, mean ASD: 3.92 ± 1.94 mm) compared to other models. The sgDefAug and GANAug approaches significantly improved model performance over ConvAug, with sgDefAug demonstrating slightly superior results (mean Dice: 0.84 ± 0.09, mean ASD: 3.14 ± 1.79 mm). The proposed methodology produced auto-contours in under 30 s, with 75% of organs showing less than 1% difference in D2% and D50% dose criteria compared to ground truth. Significance. The integration of the nnU-Net framework with our proposed novel augmentation technique effectively addresses the challenges of limited datasets and stringent time constraints in online adaptive radiotherapy for pancreatic cancer. Our approach offers a promising solution for streamlining online adaptive workflows and represents a substantial step forward in the practical application of auto-segmentation techniques in clinical radiotherapy settings., (Creative Commons Attribution license.)

Introduction: We aimed to establish if stereotactic body radiotherapy to the prostate can be delivered safely using reduced clinical target volume (CTV) to planning target volume (PTV) margins on the 1.5T MR-Linac (MRL) (Elekta, Stockholm, Sweden), in the absence of gating., Methods: Cine images taken in 3 orthogonal planes during the delivery of prostate SBRT with 36.25 Gray (Gy) in 5 fractions on the MRL were analysed. Using the data from 20 patients, the percentage of radiotherapy (RT) delivery time where the prostate position moved beyond 1, 2, 3, 4 and 5 mm in the left-right (LR), superior-inferior (SI), anterior-posterior (AP) and any direction was calculated., Results: The prostate moved less than 3 mm in any direction for 90% of the monitoring period in 95% of patients. On a per-fraction basis, 93% of fractions displayed motion in all directions within 3 mm for 90% of the fraction delivery time. Recurring motion patterns were observed showing that the prostate moved with shallow drift (most common), transient excursions and persistent excursions during treatment., Conclusion: A 3 mm CTV-PTV margin is safe to use for the treatment of 5 fraction prostate SBRT on the MRL, without gating. In the context of gating this work suggests that treatment time will not be extensively lengthened when an appropriate gating window is applied., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Westley, Alexander, Goodwin, Dunlop, Nill, Oelfke, McNair and Tree.)

HERMES is a phase II trial of MRI-guided daily-adaptive radiotherapy (MRIgART) randomising men with localised prostate cancer to either 2-fractions of SBRT with a boost to the tumour or 5-fraction SBRT. In the context of this highly innovative regime the dose delivered must be carefully considered. The first ten patients recruited to HERMES were analysed in order to establish the dose received by the targets and organs at risk (OARS) in the context of intrafraction motion. A regression analysis was performed to measure how the volume of air within the rectum might further impact rectal dose secondary to the electron return effect (ERE). One hundred percent of CTV target objectives were achieved on the MRI taken prior to beam-on-time. The post-delivery MRI showed that high-dose CTV coverage was achieved in 90% of sub-fractions (each fraction is delivered in two sub-fractions) in the 2-fraction cohort and in 88% of fractions the 5-fraction cohort. Rectal D1 cm 3 was the most exceeded constraint; three patients exceeded the D1 cm 3 < 20.8 Gy in the 2-fraction cohort and one patient exceeded the D1 cm 3 < 36 Gy in the 5-fraction cohort. The volume of rectal gas within 1 cm of the prostate was directly proportional to the increase in rectal D1 cm 3 , with a strong (R = 0.69) and very strong (R = 0.90) correlation in the 2-fraction and 5-fraction cohort respectively. Dose delivery specified in HERMES is feasible, although for some patients delivered doses to both target and OARs may vary from those planned.

Background: MR-Linac allows for daily online treatment adaptation to the observed geometry of tumor targets and organs at risk (OARs). Manual delineation for head and neck cancer (HNC) patients takes 45-75 minutes, making it unsuitable for online adaptive radiotherapy. This study aims to clinically and dosimetrically validate an in-house developed algorithm which automatically delineates the elective target volume and OARs for HNC patients in under a minute., Methods: Auto-contours were generated by an in-house model with 2D U-Net architecture trained and tested on 52 MRI scans via leave-one-out cross-validation. A randomized selection of 684 automated and manual contours (split half-and-half) was presented to an oncologist to perform a blind test and determine the clinical acceptability. The dosimetric impact was investigated for 13 patients evaluating the differences in dosage for all structures., Results: Automated contours were generated in 8 seconds per MRI scan. The blind test concluded that 114 (33%) of auto-contours required adjustments with 85 only minor and 15 (4.4%) of manual contours required adjustments with 12 only minor. Dosimetric analysis showed negligible dosimetric differences between clinically acceptable structures and structures requiring minor changes. The Dice Similarity coefficients for the auto-contours ranged from 0.66 ± 0.11 to 0.88 ± 0.06 across all structures., Conclusion: Majority of auto-contours were clinically acceptable and could be used without any adjustments. Majority of structures requiring minor adjustments did not lead to significant dosimetric differences, hence manual adjustments were needed only for structures requiring major changes, which takes no longer than 10 minutes per patient., Competing Interests: Authors VK, BE, AD, AG, TG, KHW, SN, KH, and UO declare the following financial interests/personal relationships which may be considered as potential competing interests: The Institute of Cancer Research and The Royal Marsden Hospital are members of the Elekta MR Linac Consortium. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Koteva, Eiben, Dunlop, Gupta, Gangil, Wong, Breedveld, Nill, Harrington and Oelfke.)

Purpose: Ultrahypofractionated radiation therapy (UHRT) is an effective treatment for localized prostate cancer with an acceptable toxicity profile; boosting the visible intraprostatic tumor has been shown to improve biochemical disease-free survival with no significant effect on genitourinary (GU) and gastrointestinal (GI) toxicity., Methods and Materials: HERMES is a single-center noncomparative randomized phase 2 trial in men with intermediate or lower high risk prostate cancer. Patients were allocated (1:1) to 36.25 Gy in 5 fractions over 2 weeks or 24 Gy in 2 fractions over 8 days with an integrated boost to the magnetic resonance imaging (MRI) visible tumor of 27 Gy in 2 fractions. A minimization algorithm with a random element with risk group as a balancing factor was used for participant randomization. Treatment was delivered on the Unity MR-Linac (Elekta AB) with daily online adaption. The primary endpoint was acute GU Common Terminology Criteria for Adverse Events version 5.0 toxicity with the aim of excluding a doubling of the rate of acute grade 2+ GU toxicity seen in PACE. Analysis was by treatment received and included all participants who received at least 1 fraction of study treatment. This interim analysis was prespecified (stage 1 of a 2-stage Simon design) for when 10 participants in each treatment group had completed the acute toxicity monitoring period (12 weeks after radiation therapy)., Results: Acute grade 2 GU toxicity was reported in 1 (10%) patient in the 5-fraction group and 2 (20%) patients in the 2-fraction group. No grade 3+ GU toxicities were reported., Conclusions: At this interim analysis, the rate of GU toxicity in the 2-fraction and 5-fraction treatment groups was found to be below the prespecified threshold (5/10 grade 2+) and continuation of the study to complete recruitment of 23 participants per group was recommended., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Real-time dose estimation is a key-prerequisite to enable online intra-fraction treatment adaptation in magnetic resonance (MR)-guided radiotherapy (MRgRT). It is an essential component for the assessment of the dosimetric benefits and risks of online adaptive treatments, such as multi-leaf collimator (MLC)-tracking., Purpose: We present a proof-of-concept for a software workflow for real-time dose estimation of MR-guided adaptive radiotherapy based on real-time data-streams of the linac delivery parameters and target positions., Methods: A software workflow, combining our in-house motion management software DynaTrack, a real-time dose calculation engine that connects to a research version of the treatment planning software (TPS) Monaco (v.6.09.00, Elekta AB, Stockholm, Sweden) was developed and evaluated. MR-guided treatment delivery on the Elekta Unity MR-linac was simulated with and without MLC-tracking for three prostate patients, previously treated on the Elekta Unity MR-linac (36.25 Gy/five fractions). Three motion scenarios were used: no motion, regular motion, and erratic prostate motion. Accumulated monitor units (MUs), centre of mass target position and MLC-leaf positions, were forwarded from DynaTrack at a rate of 25 Hz to a Monte Carlo (MC) based dose calculation engine which utilises the research GPUMCD-library (Elekta AB, Stockholm, Sweden). A rigid isocentre shift derived from the selected motion scenarios was applied to a bulk density-assigned session MR-image. The respective electron density used for treatment planning was accessed through the research Monaco TPS. The software workflow including the online dose reconstruction was validated against offline dose reconstructions. Our investigation showed that MC-based real-time dose calculations that account for all linac states (including MUs, MLC positions and target position) were infeasible, hence states were randomly sampled and used for calculation as follows; Once a new linac state was received, a dose calculation with 10 6 photons was started. Linac states that arrived during the time of the ongoing calculation were put into a queue. After completion of the ongoing calculation, one new linac state was randomly picked from the queue and assigned the MU accumulated from the previous state until the last sample in the queue. The queue was emptied, and the process repeated throughout treatment simulation., Results: On average 27% (23%-30%) of received samples were used in the real-time calculation, corresponding to a calculation time for one linac state of 148 ms. Median gamma pass rate (2%/3 mm local) was 100.0% (99.9%-100%) within the PTV volume and 99.1% (90.1%-99.4.0%) with a 15% dose cut off. Differences in PTVD mean , CTVD mean , RectumD 2% , and BladderD 2% (offline-online, % of prescribed dose) were below 0.64%. Beam-by-beam comparisons showed deviations below 0.07 Gy. Repeated simulations resulted in standard deviations below 0.31% and 0.12 Gy for the investigated volume and dose criteria respectively., Conclusions: Real-time dose estimation was successfully performed using the developed software workflow for different prostate motion traces with and without MLC-tracking. Negligible dosimetric differences were seen when comparing online and offline reconstructed dose, enabling online intra-fraction treatment decisions based on estimates of the delivered dose., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Objective. Respiratory motion of lung tumours and adjacent structures is challenging for radiotherapy. Online MR-imaging cannot currently provide real-time volumetric information of the moving patient anatomy, therefore limiting precise dose delivery, delivered dose reconstruction, and downstream adaptation methods. Approach. We tailor a respiratory motion modelling framework towards an MR-Linac workflow to estimate the time-resolved 4D motion from real-time data. We develop a multi-slice acquisition scheme which acquires thick, overlapping 2D motion-slices in different locations and orientations, interleaved with 2D surrogate-slices from a fixed location. The framework fits a motion model directly to the input data without the need for sorting or binning to account for inter- and intra-cycle variation of the breathing motion. The framework alternates between model fitting and motion-compensated super-resolution image reconstruction to recover a high-quality motion-free image and a motion model. The fitted model can then estimate the 4D motion from 2D surrogate-slices. The framework is applied to four simulated anthropomorphic datasets and evaluated against known ground truth anatomy and motion. Clinical applicability is demonstrated by applying our framework to eight datasets acquired on an MR-Linac from four lung cancer patients. Main results. The framework accurately reconstructs high-quality motion-compensated 3D images with 2 mm 3 isotropic voxels. For the simulated case with the largest target motion, the motion model achieved a mean deformation field error of 1.13 mm. For the patient cases residual error registrations estimate the model error to be 1.07 mm (1.64 mm), 0.91 mm (1.32 mm), and 0.88 mm (1.33 mm) in superior-inferior, anterior-posterior, and left-right directions respectively for the building (application) data. Significance. The motion modelling framework estimates the patient motion with high accuracy and accurately reconstructs the anatomy. The image acquisition scheme can be flexibly integrated into an MR-Linac workflow whilst maintaining the capability of online motion-management strategies based on cine imaging such as target tracking and/or gating., (Creative Commons Attribution license.)

Hybrid systems that combine Magnetic Resonance Imaging (MRI) and linear accelerators are available clinically to guide and adapt radiotherapy. Vendor-approved MRI sequences are provided, however alternative sequences may offer advantages. The aim of this study was to develop a systematic approach for non-vendor sequence evaluation, to determine safety, accuracy and overall clinical application of two potential sequences for bladder cancer MRI guided radiotherapy. Non-vendor sequences underwent and passed clinical image qualitative review, phantom quality assurance, and radiotherapy planning assessments. Volunteer workflow tests showed the potential for one sequence to reduce workflow time by 27% compared to the standard vendor sequence., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The Royal Marsden Hospital and The Institute of Cancer Research are members of the Elekta MR-linac Consortium, which aims to coordinate international collaborative research relating to the Elekta Unity (MR-linac). Elekta (Elekta AB, Stockholm, Sweden) and Philips (Philips, Best, the Netherlands) are commercial members of the MR-linac Consortium. Elekta financially supports consortium member institutions with research funding, education and travel costs for consortium meetings. S. Hafeez is bladder tumour site group lead within the MR-linac Consortium. No commercial financial support was received from any organisation for the submitted work., (© 2023 The Authors.)

Objective: The goal of this consensus expert opinion was to define quality assurance (QA) tests for online magnetic resonance image (MRI) guided radiotherapy (oMRgRT) systems and to define the important medical physics aspects for installation and commissioning of an oMRgRT system., Materials and Methods: Ten medical physicists and two radiation oncologists experienced in oMRgRT participated in the survey. In the first round of the consensus expert opinion, ideas on QA and commissioning were collected. Only tests and aspects different from commissioning of a CT guided radiotherapy (RT) system were considered. In the following two rounds all twelve participants voted on the importance of the QA tests, their recommended frequency and their suitability for the two oMRgRT systems approved for clinical use as well as on the importance of the aspects to consider during medical physics commissioning., Results: Twenty-four QA tests were identified which are potentially important during commissioning and routine QA on oMRgRT systems compared to online CT guided RT systems. An additional eleven tasks and aspects related to construction, workflow development and training were collected. Consensus was found for most tests on their importance, their recommended frequency and their suitability for the two approved systems. In addition, eight aspects mostly related to the definition of workflows were also found to be important during commissioning., Conclusions: A program for QA and commissioning of oMRgRT systems was developed to support medical physicists to prepare for safe handling of such systems., 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. Published by Elsevier B.V.)

Background and Purpose: The implementation of MRI-guided online adaptive radiotherapy has facilitated the extension of therapeutic radiographers' roles to include contouring, thus releasing the clinician from attending daily treatment. Following undergoing a specifically designed training programme, an online interobserver variability study was performed., Materials and Methods: 117 images from six patients treated on a MR Linac were contoured online by either radiographer or clinician and the same images contoured offline by the alternate profession. Dice similarity coefficient (DSC), mean distance to agreement (MDA), Hausdorff distance (HD) and volume metrics were used to analyse contours. Additionally, the online radiographer contours and optimised plans (n = 59) were analysed using the offline clinician defined contours. After clinical implementation of radiographer contouring, target volume comparison and dose analysis was performed on 20 contours from five patients., Results: Comparison of the radiographers' and clinicians' contours resulted in a median (range) DSC of 0.92 (0.86 - 0.99), median (range) MDA of 0.98 mm (0.2-1.7) and median (range) HD of 6.3 mm (2.5-11.5) for all 117 fractions. There was no significant difference in volume size between the two groups. Of the 59 plans created with radiographer online contours and overlaid with clinicians' offline contours, 39 met mandatory dose constraints and 12 were acceptable because 95 % of the high dose PTV was covered by 95 % dose, or the high dose PTV was within 3 % of online plan. A clinician blindly reviewed the eight remaining fractions and, using trial quality assurance metrics, deemed all to be acceptable. Following clinical implementation of radiographer contouring, the median (range) DSC of CTV was 0.93 (0.88-1.0), median (range) MDA was 0.8 mm (0.04-1.18) and HD was 5.15 mm (2.09-8.54) respectively. Of the 20 plans created using radiographer online contours overlaid with clinicians' offline contours, 18 met the dosimetric success criteria, the remaining 2 were deemed acceptable by a clinician., Conclusion: Radiographer and clinician prostate and seminal vesicle contours on MRI for an online adaptive workflow are comparable and produce clinically acceptable plans. Radiographer contouring for prostate treatment on a MR-linac can be effectively introduced with appropriate training and evaluation. A DSC threshold for target structures could be implemented to streamline future training., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Helen A McNair reports financial support was provided by National Institute for Health Research and Health Education England. Alison Tree, Angela Pathmanathan, Rosalyne Westley reports a relationship with Elekta Ltd. Alison Tree reports a relationship with Accuray Inc. Alison Tree reports a relationship with Varian Medical Systems Inc. Alison Tree, Sophie Alexander reports a relationship with Cancer Research UK that. Research at The Institute of Cancer Research is also supported by Cancer Research UK under Programme C33589/A28284 and C7224/A28724.., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: Neoadjuvant chemoradiotherapy followed by surgery is the mainstay of treatment for patients with rectal cancer. Standard clinical target volume (CTV) to planning target volume (PTV) margins of 10 mm are used to accommodate inter- and intrafraction motion of target. Treating on magnetic resonance-integrated linear accelerators (MR-linacs) allows for online manual recontouring and adaptation (MRgART) enabling the reduction of PTV margins. The aim of this study was to investigate motion of the primary CTV (CTVA; gross tumour volume and macroscopic nodes with 10 mm expansion to cover microscopic disease) in order to develop a simultaneous integrated boost protocol for use on MR-linacs., Materials and Methods: Patients suitable for neoadjuvant chemoradiotherapy were recruited for treatment on MR-linac using a two-phase technique; only the five phase 1 fractions on MR-linac were used for analysis. Intrafraction motion of CTVA was measured between pre-treatment and post-treatment MRI scans. In MRgART, isotropically expanded pre-treatment PTV margins from 1 to 10 mm were rigidly propagated to post-treatment MRI to determine overlap with 95% of CTVA. The PTV margin was considered acceptable if overlap was >95% in 90% of fractions. To understand the benefit of MRgART, the same methodology was repeated using a reference computed tomography planning scan for pre-treatment imaging., Results: In total, nine patients were recruited between January 2018 and December 2020 with T3a-T4, N0-N2, M0 disease. Forty-five fractions were analysed in total. The median motion across all planes was 0 mm, demonstrating minimal intrafraction motion. A PTV margin of 3 and 5mm was found to be acceptable in 96 and 98% of fractions, respectively. When comparing to the computed tomography reference scan, the analysis found that PTV margins to 5 and 10 mm only acceptably covered 51 and 76% of fractions, respectively., Conclusion: PTV margins can be reduced to 3-5 mm in MRgART for rectal cancer treatment on MR-linac within an simultaneous integrated boost protocol., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

The implementation of MRI-guided online adaptive radiotherapy has enabled extension of therapeutic radiographers' roles to include contouring. An offline interobserver variability study compared five radiographers' and five clinicians' contours on 10 MRIs acquired on a MR-Linac from 10 patients. All contours were compared to a "gold standard" created from an average of clinicians' contours. The median (range) DSC of radiographers' and clinicians' contours compared to the "gold standard" was 0.91 (0.86-0.96), and 0.93 (0.88-0.97) respectively illustrating non-inferiority of the radiographers' contours to the clinicians. There was no significant difference in HD, MDA or volume size between the groups., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Helen A McNair reports financial support was provided by National Institute for Health Research and Health Education England. Alison Tree, Angela Pathmanathan, Rosalyne Westley reports a relationship with Elekta Ltd. Alison Tree reports a relationship with Accuray Inc. Alison Tree reports a relationship with Varian Medical Systems Inc. Alison Tree, Sophie Alexander reports a relationship with Cancer Research UK that. Research at The Institute of Cancer Research is also supported by Cancer Research UK under Programme C33589/A28284 and C7224/A28724., (© 2022 The Author(s).)

A shift of the daily plan can mitigate target position changes that occur between daily MR acquisition and treatment for MR-linac radiotherapy, but increases the session time. We demonstrated that our workflow strategy and decision-making process, to determine whether a subsequent shift is necessary, is appropriate., 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. Alison Tree acknowledges research funding from Elekta, Varian and Accuray and honoraria/travel grants from Elekta, Accuray and Janssen. Angela Pathmanathan acknowledges honoraria from Elekta and Janssen. ICR/RMH is a member of the Elekta MR-linac Research Consortium and receives institutional support from Elekta., (© 2022 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Purpose: This study aims to develop and validate a simple geometric model of the accelerator head, from which a particle phase space can be calculated for application to fast Monte Carlo dose calculation in real-time adaptive photon radiotherapy. With this objective in view, the study investigates whether the phase space model can facilitate dose calculations which are compatible with those of a commercial treatment planning system, for convenient interoperability., Materials and Methods: A dual-source model of the head of a Versa HD accelerator (Elekta AB, Stockholm, Sweden) was created. The model used parameters chosen to be compatible with those of 6-MV flattened and 6-MV flattening filter-free photon beams in the RayStation treatment planning system (RaySearch Laboratories, Stockholm, Sweden). The phase space model was used to calculate a photon phase space for several treatment plans, and the resulting phase space was applied to the Dose Planning Method (DPM) Monte Carlo dose calculation algorithm. Simple fields and intensity-modulated radiation therapy (IMRT) treatment plans for prostate and lung were calculated for benchmarking purposes and compared with the convolution-superposition dose calculation within RayStation., Results: For simple square fields in a water phantom, the calculated dose distribution agrees to within ±2% with that from the commercial treatment planning system, except in the buildup region, where the DPM code does not model the electron contamination. For IMRT plans of prostate and lung, agreements of ±2% and ±6%, respectively, are found, with slightly larger differences in the high dose gradients., Conclusions: The phase space model presented allows convenient calculation of a phase space for application to Monte Carlo dose calculation, with straightforward translation of beam parameters from the RayStation beam model. This provides a basis on which to develop dose calculation in a real-time adaptive setting., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Background: The prostate demonstrates inter- and intra- fractional changes and thus adaptive radiotherapy would be required to ensure optimal coverage. Daily adaptive radiotherapy for MRI-guided radiotherapy can be both time and resource intensive when structure delineation is completed manually. Contours can be auto-generated on the MR-Linac via a deformable image registration (DIR) based mapping process from the reference image. This study evaluates the performance of automatically generated target structure contours against manually delineated contours by radiation oncologists for prostate radiotherapy on the Elekta Unity MR-Linac., Methods: Plans were generated from prostate contours propagated by DIR and rigid image registration (RIR) for forty fractions from ten patients. A two-dose level SIB (simultaneous integrated boost) IMRT plan is used to treat localised prostate cancer; 6000 cGy to the prostate and 4860 cGy to the seminal vesicles. The dose coverage of the PTV 6000 and PTV 4860 created from the manually drawn target structures was evaluated with each plan. If the dose objectives were met, the plan was considered successful in covering the gold standard (clinician-delineated) volume., Results: The mandatory PTV 6000 dose objective (D98% > 5580 cGy) was met in 81 % of DIR plans and 45 % of RIR plans. The SV were mapped by DIR only and for all the plans, the PTV 4860 dose objective met the optimal target (D98% > 4617 cGy). The plans created by RIR led to under-coverage of the clinician-delineated prostate, predominantly at the apex or the bladder-prostate interface., Conclusion: Plans created from DIR propagation of prostate contours outperform those created from RIR propagation. In approximately 1 in 5 DIR plans, dosimetric coverage of the gold standard PTV was not clinically acceptable. Thus, at our institution, we use a combination of DIR propagation of contours alongside manual editing of contours where deemed necessary for online treatments., 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 The Authors.)

Bladder tumour-focused magnetic resonance image-guided adaptive radiotherapy using a 1.5 Tesla MR-linac is feasible. A full online workflow adapting to anatomy at each fraction is achievable in approximately 30 min. Intra-fraction bladder filling did not compromise target coverage with the class solution employed., Competing Interests: The Royal Marsden Hospital, and The Institute of Cancer Research are members of the Elekta MR-linac Consortium, which aims to coordinate international collaborative research relating to the Elekta Unity (MR-linac). Elekta (Elekta AB, Stockholm, Sweden) and Philips (Philips, Best, Netherlands) are commercial members of the MR-linac Consortium. Elekta financially supports consortium member institutions with research funding, education, and travel costs for consortium meetings. S.H. is bladder tumour site group lead within the MR-linac Consortium. No commercial financial support was received from any organisation for the submitted work., (© 2022 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Aims: With interest in normal tissue sparing and dose-escalated radiotherapy in the treatment of inoperable locally advanced non-small cell lung cancer, this study investigated the impact of motion-managed moderate deep inspiration breath hold (mDIBH) on normal tissue sparing and dose-escalation potential and compared this to planning with a four-dimensional motion-encompassing internal target volume or motion-compensating mid-ventilation approach., Materials and Methods: Twenty-one patients underwent four-dimensional and mDIBH planning computed tomography scans. Internal and mid-ventilation target volumes were generated on the four-dimensional scan, with mDIBH target volumes generated on the mDIBH scan. Isotoxic target dose-escalation guidelines were used to generate six plans per patient: three with a target dose cap and three without. Target dose-escalation potential, normal tissue complication probability and differences in pre-specified dose-volume metrics were evaluated for the three motion-management techniques., Results: The mean total lung volume was significantly greater with mDIBH compared with four-dimensional scans. Lung dose (mean and V 21 Gy ) and mean heart dose were significantly reduced with mDIBH in comparison with four-dimensional-based approaches, and this translated to a significant reduction in heart and lung normal tissue complication probability with mDIBH. In 20/21 patients, the trial target prescription dose cap of 79.2 Gy was achievable with all motion-management techniques., Conclusion: mDIBH aids lung and heart dose sparing in isotoxic dose-escalated radiotherapy compared with four-dimensional planning techniques. Given concerns about lung and cardiac toxicity, particularly in an era of consolidation immunotherapy, reduced normal tissue doses may be advantageous for treatment tolerance and outcome., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Introduction: The Elekta Unity MR-Linac (MRL) has enabled adaptive radiotherapy (ART) for patients with head and neck cancers (HNC). Adapt-To-Shape-Lite (ATS-Lite) is a novel Adapt-to-Shape strategy that provides ART without requiring daily clinician presence to perform online target and organ at risk (OAR) delineation. In this study we compared the performance of our clinically-delivered ATS-Lite strategy against three Adapt-To-Position (ATP) variants: Adapt Segments (ATP-AS), Optimise Weights (ATP-OW), and Optimise Shapes (ATP-OS)., Methods: Two patients with HNC received radical-dose radiotherapy on the MRL. For each fraction, an ATS-Lite plan was generated online and delivered and additional plans were generated offline for each ATP variant. To assess the clinical acceptability of a plan for every fraction, twenty clinical goals for targets and OARs were assessed for all four plans., Results: 53 fractions were analysed. ATS-Lite passed 99.9% of mandatory dose constraints. ATP-AS and ATP-OW each failed 7.6% of mandatory dose constraints. The Planning Target Volumes for 54 Gy (D95% and D98%) were the most frequently failing dose constraint targets for ATP. ATS-Lite median fraction times for Patient 1 and 2 were 40 mins 9 s (range 28 mins 16 s - 47 mins 20 s) and 32 mins 14 s (range 25 mins 33 s - 44 mins 27 s), respectively., Conclusions: Our early data show that the novel ATS-Lite strategy produced plans that fulfilled 99.9% of clinical dose constraints in a time frame that is tolerable for patients and comparable to ATP workflows. Therefore, ATS-Lite, which bridges the gap between ATP and full ATS, will be further utilised and developed within our institute and it is a workflow that should be considered for treating patients with HNC on the MRL., 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: 4D and midposition MRI could inform plan adaptation in lung and abdominal MR-guided radiotherapy. We present deep learning-based solutions to overcome long 4D-MRI reconstruction times while maintaining high image quality and short scan times., Methods: Two 3D U-net deep convolutional neural networks were trained to accelerate the 4D joint MoCo-HDTV reconstruction. For the first network, gridded and joint MoCo-HDTV-reconstructed 4D-MRI were used as input and target data, respectively, whereas the second network was trained to directly calculate the midposition image. For both networks, input and target data had dimensions of 256 × 256 voxels (2D) and 16 respiratory phases. Deep learning-based MRI were verified against joint MoCo-HDTV-reconstructed MRI using the structural similarity index (SSIM) and the naturalness image quality evaluator (NIQE). Moreover, two experienced observers contoured the gross tumour volume and scored the images in a blinded study., Results: For 12 subjects, previously unseen by the networks, high-quality 4D and midposition MRI (1.25 × 1.25 × 3.3 mm 3 ) were each reconstructed from gridded images in only 28 seconds per subject. Excellent agreement was found between deep-learning-based and joint MoCo-HDTV-reconstructed MRI (average SSIM ≥ 0.96, NIQE scores 7.94 and 5.66). Deep-learning-based 4D-MRI were clinically acceptable for target and organ-at-risk delineation. Tumour positions agreed within 0.7 mm on midposition images., Conclusion: Our results suggest that the joint MoCo-HDTV and midposition algorithms can each be approximated by a deep convolutional neural network. This rapid reconstruction of 4D and midposition MRI facilitates online treatment adaptation in thoracic or abdominal MR-guided radiotherapy., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Over the last few years, magnetic resonance image-guided radiotherapy systems have been introduced into the clinic, allowing for daily online plan adaption. While quality assurance (QA) is similar to conventional radiotherapy systems, there is a need to introduce or modify measurement techniques. As yet, there is no consensus guidance on the QA equipment and test requirements for such systems. Therefore, this report provides an overview of QA equipment and techniques for mechanical, dosimetric, and imaging performance of such systems and recommendation of the QA procedures, particularly for a 1.5T MR-linac device. An overview of the system design and considerations for QA measurements, particularly the effect of the machine geometry and magnetic field on the radiation beam measurements is given. The effect of the magnetic field on measurement equipment and methods is reviewed to provide a foundation for interpreting measurement results and devising appropriate methods. And lastly, a consensus overview of recommended QA, appropriate methods, and tolerances is provided based on conventional QA protocols. The aim of this consensus work was to provide a foundation for QA protocols, comparative studies of system performance, and for future development of QA protocols and measurement methods., (© 2021 Elekta Limited. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Aims: Target delineation uncertainty is arguably the largest source of geometric uncertainty in radiotherapy. Several factors can affect it, including the imaging modality used for delineation. It is accounted for by applying safety margins to the target to produce a planning target volume (PTV), to which treatments are designed. To determine the margin, the delineation uncertainty is measured as the delineation error, and then a margin recipe used. However, there is no published evidence of such analysis for recurrent gynaecological cancers (RGC). The aims of this study were first to quantify the delineation uncertainty for RGC gross tumour volumes (GTVs) and to calculate the associated PTV margins and then to quantify the difference in GTV, delineation uncertainty and PTV margin, between a computed tomography-magnetic resonance imaging (CT-MRI) and MRI workflow., Materials and Methods: Seven clinicians delineated the GTV for 20 RGC tumours on co-registered CT and MRI datasets (CT-MRI) and on MRI alone. The delineation error, the standard deviation of distances from each clinician's outline to a reference, was measured and the required PTV margin determined. Differences between using CT-MRI and MRI alone were assessed., Results: The overall delineation error and the resulting margin were 3.1 mm and 8.5 mm, respectively, for CT-MRI, reducing to 2.5 mm and 7.1 mm, respectively, for MRI alone. Delineation errors and therefore the theoretical margins, varied widely between patients. MRI tumour volumes were on average 15% smaller than CT-MRI tumour volumes., Discussion: This study is the first to quantify delineation error for RGC tumours and to calculate the corresponding PTV margin. The determined margins were larger than those reported in the literature for similar patients, bringing into question both current margins and margin calculation methods. The wide variation in delineation error between these patients suggests that applying a single population-based margin may result in PTVs that are suboptimal for many. Finally, the reduced tumour volumes and safety margins suggest that patients with RGC may benefit from an MRI-only treatment workflow., (Copyright © 2021 The Royal College of Radiologists. All rights reserved.)

Target volume delineation uncertainty (DU) is arguably one of the largest geometric uncertainties in radiotherapy that are accounted for using planning target volume (PTV) margins. Geometrical uncertainties are typically derived from a limited sample of patients. Consequently, the resultant margins are not tailored to individual patients. Furthermore, standard PTVs cannot account for arbitrary anisotropic extensions of the target volume originating from DU. We address these limitations by developing a method to measure DU for each patient by a single clinician. This information is then used to produce PTVs that account for each patient's unique DU, including any required anisotropic component. We do so using a two-step uncertainty evaluation strategy that does not rely on multiple samples of data to capture the DU of a patient's gross tumour volume (GTV) or clinical target volume. For simplicity, we will just refer to the GTV in the following. First, the clinician delineates two contour sets; one which bounds all voxels believed to have a probability of belonging to the GTV of 1, while the second includes all voxels with a probability greater than 0. Next, one specifies a probability density function for the true GTV boundary position within the boundaries of the two contours. Finally, a patient-specific PTV, designed to account for all systematic errors, is created using this information along with measurements of the other systematic errors. Clinical examples indicate that our margin strategy can produce significantly smaller PTVs than the van Herk margin recipe. Our new radiotherapy target delineation concept allows DUs to be quantified by the clinician for each patient, leading to PTV margins that are tailored to each unique patient, thus paving the way to a greater personalisation of radiotherapy.

The drive towards hypofractionated prostate radiotherapy is motivated by a low alpha/beta ratio for prostate cancer (1 to 3 Gy) compared to surrounding organs at risk, implying an improved therapeutic ratio with increasing dose per fraction. Early evidence from studies of ultrahypofractionated (UHF) prostate HDR brachytherapy has shown good tolerability in terms of normal tissue toxicities and clinical outcomes similar to conventional fractionation schedules. MR-guided stereotactic body radiotherapy (SBRT) with online plan adaptation and real-time tumour imaging may enable UHF doses to be delivered to the prostate safely, without the invasiveness of brachytherapy. The feasibility of UHF prostate treatment planning for the Unity MR-Linac (MRL, Elekta AB, Stockholm) was investigated for target prescriptions and planning constraints derived from the HDR brachytherapy and SBRT literature. Monaco 5.40 (Elekta) was used to generate MRL step-and-shoot IMRT plans for three dose fractionation protocols (5, 2 and 1 fractions), for ten randomly selected previously treated prostate cancer patients. Of the ten plans per UHF scheme, all clinical goals were met in all cases for 5 fractions, and in six cases for both 2 and 1 fraction schemes. PTV D95% was compromised by up to 6.4% and 3.9% of the associated target dose for 2 and 1 fraction plans respectively. There were two cases of PTV D95% compromise greater than a 5% dose decrease for the 2 fraction plans. The study suggests feasibility of the UHF treatment planning approaches if combined with real-time motion mitigation strategies., (© 2020 The Authors.)

Whole bladder magnetic resonance image-guided radiotherapy using the 1.5 Telsa MR-linac is feasible. Full online adaptive planning workflow based on the anatomy seen at each fraction was performed. This was delivered within 45 min. Intra-fraction bladder filling did not compromise target coverage. Patients reported acceptable tolerance of treatment., Competing Interests: The Royal Marsden Hospital and the Institute of Cancer Research are members of the Elekta MR-linac Consortium, which aims to coordinate international collaborative research relating to the Elekta Unity (MR-linac). Elekta (Elekta AB, Stockholm, Sweden) and Philips (Philips, Best, Netherlands) are commercial members of the MR-linac Consortium. Elekta financially supports consortium member institutions with research funding, education, and travel costs for consortium meetings. No commercial financial support was received from any organisation for the submitted work. AH, IH, AD, HB, LB, JC, CC, TH, RL, DM, HM, AM, JM, GS, and SN, have no other conflicts to disclose. HM also reports grant funding from a National Institute for Health Research and Health Education England (NIHR & HEE), Senior Clinical Lecturer award. TM also reports grant from Lister Institute of Preventive Medicine, outside the submitted work. EH is supported by a Cancer Research UK Centres Network Accelerator Award Grant (A21993) to the ART-NET consortium, other grants from Cancer Research UK during the conduct of the study; grants from Accuray Inc., grants from Varian Medical Systems Inc., outside the submitted work. UO also reports grants from Cancer Research UK. RH also reports non-financial support from Janssen, grants and personal fees from MSD, personal fees from Bristol Myers Squibb, grants from Cancer Research UK, other from Nektar Therapeutics, personal fees and non-financial support from Roche outside the submitted work. SH also reports non-financial support from Merck Sharp & Dohme (MSD), personal fees and non-financial support from Roche outside the submitted work., (© 2020 The Authors.)

Breathing motion is challenging for radiotherapy planning and delivery. This requires advanced four-dimensional (4D) imaging and motion mitigation strategies and associated validation tools with known deformations. Numerical phantoms such as the XCAT provide reproducible and realistic data for simulation-based validation. However, the XCAT generates partially inconsistent and non-invertible deformations where tumours remain rigid and structures can move through each other. We address these limitations by post-processing the XCAT deformation vector fields (DVF) to generate a breathing phantom with realistic motion and quantifiable deformation. An open-source post-processing framework was developed that corrects and inverts the XCAT-DVFs while preserving sliding motion between organs. Those post-processed DVFs are used to warp the first XCAT-generated image to consecutive time points providing a 4D phantom with a tumour that moves consistently with the anatomy, the ability to scale lung density as well as consistent and invertible DVFs. For a regularly breathing case, the inverse consistency of the DVFs was verified and the tumour motion was compared to the original XCAT. The generated phantom and DVFs were used to validate a motion-including dose reconstruction (MIDR) method using isocenter shifts to emulate rigid motion. Differences between the reconstructed doses with and without lung density scaling were evaluated. The post-processing framework produced DVFs with a maximum [Formula: see text]-percentile inverse-consistency error of 0.02 mm. The generated phantom preserved the dominant sliding motion between the chest wall and inner organs. The tumour of the original XCAT phantom preserved its trajectory while deforming consistently with the underlying tissue. The MIDR was compared to the ground truth dose reconstruction illustrating its limitations. MIDR with and without lung density scaling resulted in small dose differences up to 1 Gy (prescription 54 Gy). The proposed open-source post-processing framework overcomes important limitations of the original XCAT phantom and makes it applicable to a wider range of validation applications within radiotherapy.

Background and Purpose: Combined photon intensity-modulated radiotherapy (IMRT) and sequential dose-escalated carbon ion beam therapy (IBT) is a technically advanced treatment option for head and neck malignancies. We proposed and evaluated an integrated planning strategy as opposed to an established and largely separated planning workflow., Materials and Methods: Ten patients with representative malignancies of the head and neck region underwent combined carbon-photon radiotherapy (RT) in our facilities. Clinical plans were created according to the separated workflow with independent optimization stages for both modalities. Experimental plans incorporated the existing carbon IBT dose distribution into the optimization stage of a step-and-shoot photon IMRT (bias dose planning)., Results: Cumulative dose distributions showed statistically significant differences between the two planning strategies and were predominantly in favor of the integrated approach. As such, target irradiation was generally maintained or even improved in a subset of metrics, while normal tissue sparing was widely enhanced; for instance, in the ipsilateral temporal lobe with median D mean of -16% (p < 0.001). Maximum doses D 1% (with adjustment for different fractionation) fell below thresholds for toxicity risk in a minority of instances, where they were previously exceeded. Integral dose did not differ significantly., Conclusions: Our findings indicate that combination planning of carbon-photon RT for head and neck malignancies may benefit from a proposed bias dose method, yielding favorable dose distribution characteristics and a streamlined planning workflow with fewer plan revisions. Further research is necessary to validate these observations in terms of robustness and their potential for higher tumor control., 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., (© 2020 The Author(s).)

Respiratory-gated radiotherapy treatments of lung tumors reduce the irradiated normal tissue volume and potentially lower the risk of side effects. However, in clinical routine, the gating signal is usually derived from external markers or other surrogate signals and may not always correlate well with the actual tumor position. This study uses the kV-imaging system of a LINAC in combination with a multiple template matching algorithm for markerless real-time detection of the tumor position in a dynamic anthropomorphic porcine lung phantom. The tumor was realized by a small container filled with polymer dosimetry gel, the so-called gel tumor. A full end-to-end test for a gated treatment was performed and the geometric and dosimetric accuracy was validated. The accuracy of the tumor detection algorithm in SI- direction was found to be [Formula: see text] mm and the gel tumor was automatically detected in 98 out of 100 images. The measured 3D dose distribution showed a uniform coverage of the gel tumor and comparison with the treatment plan revealed a high 3D [Formula: see text]-passing rate of [Formula: see text] ([Formula: see text]). The simulated treatment confirmed the employed margin sizes for residual motion within the gating window and serves as an end-to-end test for a gated treatment based on a markerless fluoroscopic real-time tumor detection.

Previous work has shown that PRESAGE ® can be used successfully to perform 3D dosimetric measurements of complex radiotherapy treatments. However, measurements near the sample edges are known to be difficult to achieve. This is an issue when the doses at air-material interfaces are of interest, for example when investigating the electron return effect (ERE) present in treatments delivered by magnetic resonance (MR)-linac systems. To study this effect, a set of 3.5 cm-diameter cylindrical PRESAGE ® samples was uniformly irradiated with multiple dose fractions, using either a conventional linac or an MR-linac. The samples were imaged between fractions using an optical-CT, to read out the corresponding accumulated doses. A calibration between TPS-predicted dose and optical-CT pixel value was determined for individual dosimeters as a function of radial distance from the axis of rotation. This data was used to develop a correction that was applied to four additional samples of PRESAGE ® of the same formulation, irradiated with 3D-CRT and IMRT treatment plans, to recover significantly improved 3D measurements of dose. An alternative strategy was also tested, in which the outer surface of the sample was physically removed prior to irradiation. Results show that for the formulation studied here, PRESAGE ® samples have a central region that responds uniformly and an edge region of 6-7 mm where there is gradual increase in dosimeter response, rising to an over-response of 24%-36% at the outer boundary. This non-uniform dose response increases in both extent and magnitude over time. Both mitigation strategies investigated were successful. In our four exemplar studies, we show how discrepancies at edges are reduced from 13%-37% of the maximum dose to between 2 and 8%. Quantitative analysis shows that the 3D gamma passing rates rise from 90.4, 69.3, 63.7 and 43.6% to 97.3, 99.9, 96.7 and 98.9% respectively.

Introduction: MR-guided adapted radiotherapy (MRgART) using a high field MR-linac has recently become available. We report the estimated delivered fractional dose of the first five prostate cancer patients treated at our centre using MRgART and compare this to C-Arm linac daily Image Guided Radiotherapy (IGRT)., Methods: Patients were treated using adapted treatment plans shaped to their daily anatomy. The treatments were recalculated on an MR image acquired immediately prior to treatment delivery in order to estimate the delivered fractional dose. C-arm linac non-adapted VMAT treatment plans were recalculated on the same MR images to estimate the fractional dose that would have been delivered using conventional radiotherapy techniques using a daily IGRT protocol., Results: 95% and 93% of mandatory target coverage objectives and organ at risk dose constraints were achieved by MRgART and C-arm linac delivered dose estimates, respectively. Both delivery techniques were estimated to have achieved 98% of mandatory Organ At Risk (OAR) dose constraints whereas for the target clinical goals, 86% and 80% were achieved by MRgART and C-arm linac delivered dose estimates., Conclusions: Prostate MRgART can be delivered using the a high field MR-linac. Radiotherapy performed on a C-arm linac offers a good solution for prostate cancer patients who present with favourable anatomy at the time of reference imaging and demonstrate stable anatomy throughout the course of their treatment. For patients with critical OARs abutting target volumes on their reference image we have demonstrated the potential for a target dose coverage improvement for MRgART compared to C-arm linac treatment., 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., (© 2020 The Authors.)

Background and Purpose: Anatomical changes during external beam radiotherapy prevent the accurate delivery of the intended dose distribution. Resolving the delivered dose, which is currently unknown, is crucial to link radiotherapy doses to clinical outcomes and ultimately improve the standard of care., Material and Methods: In this study, we present a dose reconstruction workflow based on data routinely acquired during MR-guided radiotherapy. It employs 3D MR images, 2D cine MR images and treatment machine log files to calculate the delivered dose taking intrafractional motion into account. The developed pipeline was used to measure anatomical changes and assess their dosimetric impact in 89 prostate radiotherapy fractions delivered with a 1.5 T MR-linac at our institute., Results: Over the course of radiation delivery, the CTV shifted 0.6 mm ± 2.1 mm posteriorly and 1.3 mm ± 1.5 mm inferiorly. When extrapolating the dose changes in each case to 20 fractions, the mean clinical target volume D 98% and clinical target volume D 50% dose-volume metrics decreased by 1.1 Gy ± 1.6 Gy and 0.1 Gy ± 0.2 Gy, respectively. Bladder D 3% did not change (0.0 Gy ± 1.2 Gy), while rectum D 3% decreased by 1.0 Gy ± 2.0 Gy. Although anatomical changes and their dosimetric impact were small in the majority of cases, large intrafractional motion caused the delivered dose to substantially deviate from the intended plan in some fractions., Conclusions: The presented end-to-end workflow is able to reliably, non-invasively and automatically reconstruct the delivered prostate radiotherapy dose by processing MR-linac treatment log files and online MR images. In the future, we envision this workflow to be adapted to other cancer sites and ultimately to enter widespread clinical use., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Several studies have demonstrated potential improvements in treatment time through the use of dynamic arcs for delivery of stereotactic body radiation therapy (SBRT) on Cyberknife. However, the delivery system has a finite accuracy, so that potential exists for dosimetric uncertainties. This study estimates the expected dosimetric accuracy of dynamic delivery of SBRT, based on realistic estimates of the uncertainties in delivery parameters., Methods: Five SBRT patient cases (prostate A - conventional, prostate B - brachytherapy-type, lung, liver, partial left breast) were retrospectively studied. Treatment plans were produced for a fixed arc trajectory using fluence optimization, segmentation, and direct aperture optimization. Dose rate uncertainty was modeled as a smoothly varying random fluctuation of ± 1.0%, ±2.0% or ± 5.0% over a time period of 10, 30 or 60 s. Multileaf collimator uncertainty was modeled as a lag in position of each leaf up to 0.25 or 0.5 mm. Robot pointing error was modeled as a shift of the target location, with the direction of the shift chosen as a random angle with respect to the multileaf collimator and with a random magnitude in the range 0.0-1.0 mm at the delivery nodes and with an additional random magnitude of 0.5-1.0 mm in between the delivery nodes. The impact of the errors was investigated using dose-volume histograms., Results: Uncertainty in dose rate has the effect of varying the total monitor units delivered, which in turn produces a variation in mean dose to the planning target volume. The random sampling of dose rate error produces a distribution of mean doses with a standard deviation proportional to the magnitude of the dose rate uncertainty. A lag in multileaf collimator position of 0.25 or 0.5 mm produces a small impact on the delivered dose. In general, an increase in the PTV mean dose of around 1% is observed. An error in robot pointing of the order of 1 mm produces a small increase in dose inhomogeneity to the planning target volume, sometimes accompanied by an increase in mean dose by around 1%., Conclusions: Based upon the limited data available on the dose rate stability and geometric accuracy of the Cyberknife system, this study estimates that dynamic arc delivery can be accomplished with sufficient accuracy for clinical application. Dose rate variation produces a change in dose to the planning target volume according to the perturbation of total monitor units delivered, while multileaf collimator lag and robot pointing error typically increase the mean dose to the planning target volume by up to 1%., (© 2020 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Objectives: To systematically identify the preferred magnetic resonance imaging (MRI) sequences following volunteer imaging on a 1.5 Tesla (T) MR-Linear Accelerator (MR Linac) for future protocol development., Methods: Non-patient volunteers were recruited to a Research and Ethics committee approved prospective MR-only imaging study on a 1.5T MR Linac system. Volunteers attended 1-3 imaging sessions that included a combination of mDixon, T1w, T2w sequences using 2-dimensional (2D) and 3-dimensional (3D) acquisitions. Each sequence was acquired over 2-7 minutes and reviewed by a panel of 3 observers to evaluate image quality using a visual grading analysis based on a 4-point Likert scale. Sequences were acquired and modified iteratively until deemed fit for purpose (online image matching or re-planning) and all observers agreed they were suitable in 3 volunteers., Results: 26 volunteers underwent 31 imaging sessions of six general anatomical regions. Images were acquired in one or two of six general anatomical regions: male pelvis (n = 9), female pelvis (n = 4), chestwall/breast (n = 5), lung/oesophagus (n = 5), abdomen (n = 3) and head and neck (n = 5). Images were acquired using a pre-defined exam-card that on average, included six sequences (range 2-10), with a maximum scan time of approximately one hour. The majority of observers preferred T2-weighted sequences. The thorax teams were the only groups to prefer T1-weighted imaging., Conclusions: An iterative process identified sequence agreement in all anatomical regions. These sequences will now be evaluated in patient volunteers., Advances in Knowledge: This manuscript is the first publication sharing the results of the first systematic selection of MRI sequences for use in on-board MRI-guided radiotherapy by end-users (therapeutic radiographers and clinical oncologists) in healthy volunteers., (© 2019 The Authors.)

Purpose: The use of dynamic arcs for delivery of stereotactic body radiation therapy (SBRT) on Cyberknife is investigated, with a view to improving treatment times. This study investigates the required modeling of robot and multileaf collimator (MLC) motion between control points in the trajectory and then uses this to develop an optimization method for treatment planning of a dynamic arc with Cyberknife. The resulting plans are compared in terms of dose-volume histograms and estimated treatment times with those produced by a conventional beam arrangement., Methods: Five SBRT patient cases (prostate A - conventional, prostate B - brachytherapy-type, lung, liver, and partial left breast) were retrospectively studied. A suitable arc trajectory with control points spaced at 5° was proposed and treatment plans were produced for typical clinical protocols. The optimization consisted of a fluence optimization, segmentation, and direct aperture optimization using a gradient descent method. Dose delivered by the moving MLC was either taken to be the dose delivered discretely at the control points or modeled using effective fluence delivered between control points. The accuracy of calculated dose was assessed by recalculating after optimization using five interpolated beams and 100 interpolated apertures between each optimization control point. The resulting plans were compared using dose-volume histograms and estimated treatment times with those for a conventional Cyberknife beam arrangement., Results: If optimization is performed based on discrete doses delivered at the arc control points, large differences of up to 40% of the prescribed dose are seen when recalculating with interpolation. When the effective fluence between control points is taken into account during optimization, dosimetric differences are <2% for most structures when the plans are recalculated using intermediate nodes, but there are differences of up to 15% peripherally. Treatment plan quality is comparable between the arc trajectory and conventional body path. All plans meet the relevant clinical goals, with the exception of specific structures which overlap with the planning target volume. Median estimated treatment time is 355 s (range 235-672 s) for arc delivery and 675 s (range 554-1025 s) for conventional delivery., Conclusions: The method of using effective fluence to model MLC motion between control points is sufficiently accurate to provide for accurate inverse planning of dynamic arcs with Cyberknife. The proposed arcing method produces treatment plans with comparable quality to the body path, with reduced estimated treatment delivery time., (© 2019 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

CT-based radiotherapy workflow is limited by poor soft tissue definition in the pelvis and reliance on rigid registration methods. Current image-guided radiotherapy and adaptive radiotherapy models therefore have limited ability to improve clinical outcomes. The advent of MRI-guided radiotherapy solutions provides the opportunity to overcome these limitations with the potential to deliver online real-time MRI-based plan adaptation on a daily basis, a true "plan of the day." This review describes the application of MRI guided radiotherapy in two pelvic tumour sites likely to benefit from this approach.

MR-guided radiotherapy treatment planning utilises the high soft-tissue contrast of MRI to reduce uncertainty in delineation of the target and organs at risk. Replacing 4D-CT with MRI-derived synthetic 4D-CT would support treatment plan adaptation on hybrid MR-guided radiotherapy systems for inter- and intrafractional differences in anatomy and respiration, whilst mitigating the risk of CT to MRI registration errors. Three methods were devised to calculate synthetic 4D and midposition (time-weighted mean position of the respiratory cycle) CT from 4D-T1w and Dixon MRI. The first approach employed intensity-based segmentation of Dixon MRI for bulk-density assignment (sCT D ). The second step added spine density information using an atlas of CT and Dixon MRI (sCT DS ). The third iteration used a polynomial function relating Hounsfield units and normalised T1w image intensity to account for variable lung density (sCT DSL ). Motion information in 4D-T1w MRI was applied to generate synthetic CT in midposition and in twenty respiratory phases. For six lung cancer patients, synthetic 4D-CT was validated against 4D-CT in midposition by comparison of Hounsfield units and dose-volume metrics. Dosimetric differences found by comparing sCT D,DS,DSL and CT were evaluated using a Wilcoxon signed-rank test (p   =  0.05). Compared to sCT D and sCT DS , planning on sCT DSL significantly reduced absolute dosimetric differences in the planning target volume metrics to less than 98 cGy (1.7% of the prescribed dose) on average. When comparing sCT DSL and CT, average radiodensity differences were within 97 Hounsfield units and dosimetric differences were significant only for the planning target volume D99% metric. All methods produced clinically acceptable results for the organs at risk in accordance with the UK SABR consensus guidelines and the LungTech EORTC phase II trial. The overall good agreement between sCT DSL and CT demonstrates the feasibility of employing synthetic 4D-CT for plan adaptation on hybrid MR-guided radiotherapy systems.

Objectives: To determine the potential for dose escalation to a biological equivalent dose BED 10 ≅ 100 Gy in hypofractionated radiotherapy for locally advanced pancreatic cancer (LAPC)., Materials and Methods: Ten unselected LAPC patients were retrospectively included in the study. Two fractionation regimens were compared (5 and 15 fractions). The aim was to cover 95% of the Planning Target Volume (PTV) with a BED 10  = 54 Gy (base dose = 33 Gy in 5 fractions, 42.5 Gy in 15 fractions) whilst respecting organs-at-risk (OAR) constraints. Once the highest PTV coverage was achieved dose escalation to a BED 10 ≅ 100 Gy (escalated dose = 50 Gy in 5 fractions, 67.5 Gy in 15 fractions) was attempted, limiting the PTV maximum dose to 130% of the escalated dose., Results: In 5 fractions, 95% PTV coverage by both base and escalated doses could be achieved for one patient with PTV more than 1 cm away from OAR. 95% and 90% PTV coverage by the base dose was achieved in one and two patients respectively. In all other patients, coverage even by the base dose had to be compromised to comply with OAR constraints. In 15 fractions, 95% PTV coverage by the base dose was feasible for all patients except one. Dose escalation allowed improvement in target coverage by the base dose in both fractionation regimen whilst covering a sub-volume of the PTV with a BED 10 ≅ 100 Gy. Both fractionation schemes were equivalent in terms of dose escalation potential., Conclusion: LAPC patients with OAR close to the PTV are generally not eligible for hypofractionation with dose escalation. However, this planning study shows that it is possible to cover PTV sub-volumes with a BED 10 ≅ 100 Gy in addition to delivering a BED 10  = 54 Gy to 90-95% of the PTV as commonly prescribed to this population. Combined with an adaptive approach, this may maximize PTV coverage by a high BED on days with favourable anatomy.

On-treatment imaging in radiotherapy has evolved over the last 60 years, bringing with it changes in the roles of radiographers, radiologists and oncologists. The ability to acquire and interpret high quality images (2D kilovoltage and megavoltage imaging and 3D CT and cone-beam CT) for radiotherapy planning and delivery requires therapy radiographers to have skills and knowledge that overlap with those of diagnostic radiographers. With the implementation of MRI-guided radiotherapy, treatment radiographers and clinical oncologists are exploring new territory, requiring truly collaborative working practices with their radiology partners. This short communication introduces the first images acquired using the hybrid MR Linac at our institution., (Copyright © 2018 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.)

The Cyberknife system (Accuray Inc., Sunnyvale, CA) enables radiotherapy using stereotactic ablative body radiotherapy (SABR) with a large number of non-coplanar beam orientations. Recently, a multileaf collimator has also been available to allow flexibility in field shaping. This work aims to evaluate the quality of treatment plans obtainable with the multileaf collimator. Specifically, the aim is to find a subset of beam orientations from a predetermined set of candidate directions, such that the treatment quality is maintained but the treatment time is reduced. An evolutionary algorithm is used to successively refine a randomly selected starting set of beam orientations. By using an efficient computational framework, clinically useful solutions can be found in several hours. It is found that 15 beam orientations are able to provide treatment quality which approaches that of the candidate beam set of 110 beam orientations, but with approximately half of the estimated treatment time. Choice of an efficient subset of beam orientations offers the possibility to improve the patient experience and maximise the number of patients treated., (Copyright © 2018. Published by Elsevier Ltd.)

Background and Purpose: The superior soft-tissue contrast of 4D-T2w MRI motivates its use for delineation in radiotherapy treatment planning. We address current limitations of slice-selective implementations, including thick slices and artefacts originating from data incompleteness and variable breathing., Materials and Methods: A method was developed to calculate midposition and 4D-T2w images of the whole thorax from continuously acquired axial and sagittal 2D-T2w MRI (1.5 × 1.5 × 5.0 mm 3 ). The method employed image-derived respiratory surrogates, deformable image registration and super-resolution reconstruction. Volunteer imaging and a respiratory motion phantom were used for validation. The minimum number of dynamic acquisitions needed to calculate a representative midposition image was investigated by retrospectively subsampling the data (10-30 dynamic acquisitions)., Results: Super-resolution 4D-T2w MRI (1.0 × 1.0 × 1.0 mm 3 , 8 respiratory phases) did not suffer from data incompleteness and exhibited reduced stitching artefacts compared to sorted multi-slice MRI. Experiments using a respiratory motion phantom and colour-intensity projection images demonstrated a minor underestimation of the motion range. Midposition diaphragm differences in retrospectively subsampled acquisitions were <1.1 mm compared to the full dataset. 10 dynamic acquisitions were found sufficient to generate midposition MRI., Conclusions: A motion-modelling and super-resolution method was developed to calculate high quality 4D/midposition T2w MRI from orthogonal 2D-T2w MRI., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

2D cine MR imaging may be utilized to monitor rapidly moving tumors and organs-at-risk for real-time adaptive radiotherapy. This study systematically investigates the impact of geometric imaging parameters on the ability of 2D cine MR imaging to guide template-matching-driven autocontouring of lung tumors and abdominal organs. Abdominal 4D MR images were acquired of six healthy volunteers and thoracic 4D MR images were obtained of eight lung cancer patients. At each breathing phase of the images, the left kidney and gallbladder or lung tumor, respectively, were outlined as volumes of interest. These images and contours were used to create artificial 2D cine MR images, while simultaneously serving as 3D ground truth. We explored the impact of five different imaging parameters (pixel size, slice thickness, imaging plane orientation, number and relative alignment of images as well as strategies to create training images). For each possible combination of imaging parameters, we generated artificial 2D cine MR images as training and test images. A template-matching algorithm used the training images to determine the tumor or organ position in the test images. Subsequently, a 3D base contour was shifted to the determined position and compared to the ground truth via centroid distance and Dice similarity coefficient. The median centroid distance between adapted and ground truth contours was 1.56 mm for the kidney, 3.81 mm for the gallbladder and 1.03 mm for the lung tumor (median Dice similarity coefficient: 0.95, 0.72 and 0.93). We observed that a decrease in image resolution led to a modest decrease in localization accuracy, especially for the small gallbladder. However, for all volumes of interest localization accuracy varied substantially more between subjects than due to the different imaging parameters. Automated tumor and organ localization using 2D cine MR imaging and template-matching-based autocontouring is robust against variation of geometric imaging parameters. Future work and optimization efforts of 2D cine MR imaging for real-time adaptive radiotherapy is needed to characterize the influence of sequence- and anatomical site-specific imaging contrast.

Adaptive radiotherapy (ART) strategies systematically monitor variations in target and neighbouring structures to inform treatment-plan modification during radiotherapy. This is necessary because a single plan designed before treatment is insufficient to capture the actual dose delivered to the target and adjacent critical structures during the course of radiotherapy. Magnetic resonance imaging (MRI) provides superior soft-tissue image contrast over current standard X-ray-based technologies without additional radiation exposure. With integrated MRI and radiotherapy platforms permitting motion monitoring during treatment delivery, it is possible that adaption can be informed by real-time anatomical imaging. This allows greater treatment accuracy in terms of dose delivered to target with smaller, individualised treatment margins. The use of functional MRI sequences would permit ART to be informed by imaging biomarkers, so allowing both personalised geometric and biological adaption. In this review, we discuss ART solutions enabled by MRI guidance and its potential gains for our patients across tumour types., (Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Margins are employed in radiotherapy treatment planning to mitigate the dosimetric effects of geometric uncertainties for the clinical target volume (CTV). Unfortunately, whilst the use of margins can increase the probability that sufficient dose is delivered to the CTV, it can also result in delivering high dose of radiation to surrounding organs at risk (OARs). We expand on our previous work on beam-dependent margins and propose a novel adaptive margin concept, where margins are moulded away from selected OARs for better OAR-high-dose sparing, whilst maintaining similar dose coverage probability to the CTV. This, however, comes at a cost of a larger irradiation volume, and thus can negatively impact other structures. We investigate the impact of the adaptive margin concept when applied to prostate radiotherapy treatments, and compare treatment plans generated using our beam-dependent margins without adaptation, with adaption from the rectum and with adaptation from both the rectum and bladder. Five prostate patients were used in this planning study. All plans achieved similar dose coverage probability, and were able to ensure at least 90% population coverage with the target receiving at least 95% of the prescribed dose to [Formula: see text]. We observed overall better high-dose sparing to OARs that were considered when using the adapted beam-dependent PTVs, with the degree of sparing dependent on both the number of OARs under consideration as well as the relative position between the CTV and the OARs.

Owing to its excellent soft-tissue contrast, magnetic resonance (MR) imaging has found an increased application in radiation therapy (RT). By harnessing these properties for treatment planning, automated segmentation methods can alleviate the manual workload burden to the clinical workflow. We investigated atlas-based segmentation methods of organs at risk (OARs) in the head and neck (H&N) region using one approach that selected the most similar atlas from a library of segmented images and two multi-atlas approaches. The latter were based on weighted majority voting and an iterative atlas-fusion approach called STEPS. We built the atlas library from pre-treatment T1-weighted MR images of 12 patients with manual contours of the parotids, spinal cord and mandible, delineated by a clinician. Following a leave-one-out cross-validation strategy, we measured the geometric accuracy by calculating Dice similarity coefficients (DSC), standard and 95% Hausdorff distances (HD and HD95), and the mean surface distance (MSD), whereby the manual contours served as the gold standard. To benchmark the algorithm, we determined the inter-observer variability (IOV) between three observers. To investigate the dosimetric effect of segmentation inaccuracies, we implemented an auto-planning strategy within the treatment planning system Monaco (Elekta AB, Stockholm, Sweden). For each set of auto-segmented OARs, we generated a plan for a 9-beam step and shoot intensity modulated RT treatment, designed according to our institution's clinical H&N protocol. Superimposing the dose distributions on the gold standard OARs, we calculated dose differences to OARs caused by delineation differences between auto-segmented and gold standard OARs. We investigated the correlations between geometric and dosimetric differences. The mean DSC was larger than 0.8 and the mean MSD smaller than 2 mm for the multi-atlas approaches, resulting in a geometric accuracy comparable to previously published results and within the range of the IOV. While dosimetric differences could be as large as 23% of the clinical goal, treatment plans fulfilled all imposed clinical goals for the gold standard OARs. Correlations between geometric and dosimetric measures were low with R 2   <  0.5. The geometric accuracy and the ability to achieve clinically acceptable treatment plans indicate the suitability of using atlas-based contours for RT treatment planning purposes. The low correlations between geometric and dosimetric measures suggest that geometric measures alone are not sufficient to predict the dosimetric impact of segmentation inaccuracies on treatment planning for the data utilised in this study.

Combined radiotherapy (RT) and hyperthermia (HT) treatments may improve treatment outcome by heat induced radio-sensitisation. We propose an empirical cell survival model (AlphaR model) to describe this multimodality therapy. The model is motivated by the observation that heat induced radio-sensitisation may be explained by a reduction in the DNA damage repair capacity of heated cells. We assume that this repair is only possible up to a threshold level above which survival will decrease exponentially with dose. Experimental cell survival data from two cell lines (HCT116, Cal27) were considered along with that taken from the literature (baby hamster kidney [BHK] and Chinese hamster ovary cells [CHO]) for HT and combined RT-HT. The AlphaR model was used to study the dependence of clonogenic survival on treatment temperature, and thermal dose R 2  ≥ 0.95 for all fits). For HT survival curves (0-80 CEM43 at 43.5-57 °C), the number of free fit AlphaR model parameters could be reduced to two. Both parameters increased exponentially with temperature. We derived the relative biological effectiveness (RBE) or HT treatments at different temperatures, to provide an alternative description of thermal dose, based on our AlphaR model. For combined RT-HT, our analysis is restricted to the linear quadratic arm of the model. We show that, for the range used (20-80 CEM43, 0-12 Gy), thermal dose is a valid indicator of heat induced radio-sensitisation, and that the model parameters can be described as a function thereof. Overall, the proposed model provides a flexible framework for describing cell survival curves, and may contribute to better quantification of heat induced radio-sensitisation, and thermal dose in general.

Dosimetric quality assurance (QA) of the new Elekta Unity (MR-linac) will differ from the QA performed of a conventional linac due to the constant magnetic field, which creates an electron return effect (ERE). In this work we aim to validate PRESAGE ® dosimetry in a transverse magnetic field, and assess its use to validate the research version of the Monaco TPS of the MR-linac. Cylindrical samples of PRESAGE ® 3D dosimeter separated by an air gap were irradiated with a cobalt-60 unit, while placed between the poles of an electromagnet at 0.5 T and 1.5 T. This set-up was simulated in EGSnrc/Cavity Monte Carlo (MC) code and relative dose distributions were compared with measurements using 1D and 2D gamma criteria of 3% and 1.5 mm. The irradiation conditions were adapted for the MR-linac and compared with Monaco TPS simulations. Measured and EGSnrc/Cavity simulated profiles showed good agreement with a gamma passing rate of 99.9% for 0.5 T and 99.8% for 1.5 T. Measurements on the MR-linac also compared well with Monaco TPS simulations, with a gamma passing rate of 98.4% at 1.5 T. Results demonstrated that PRESAGE ® can accurately measure dose and detect the ERE, encouraging its use as a QA tool to validate the Monaco TPS of the MR-linac for clinically relevant dose distributions at tissue-air boundaries.

Radiation therapy to the prostate involves increasingly sophisticated delivery techniques and changing fractionation schedules. With a low estimated α/β ratio, a larger dose per fraction would be beneficial, with moderate fractionation schedules rapidly becoming a standard of care. The integration of a magnetic resonance imaging (MRI) scanner and linear accelerator allows for accurate soft tissue tracking with the capacity to replan for the anatomy of the day. Extreme hypofractionation schedules become a possibility using the potentially automated steps of autosegmentation, MRI-only workflow, and real-time adaptive planning. The present report reviews the steps involved in hypofractionated adaptive MRI-guided prostate radiation therapy and addresses the challenges for implementation., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Combined radiotherapy and hyperthermia offer great potential for the successful treatment of radio-resistant tumours through thermo-radiosensitization. Tumour response heterogeneity, due to intrinsic, or micro-environmentally induced factors, may greatly influence treatment outcome, but is difficult to account for using traditional treatment planning approaches. Systems oncology simulation, using mathematical models designed to predict tumour growth and treatment response, provides a powerful tool for analysis and optimization of combined treatments. We present a framework that simulates such combination treatments on a cellular level. This multiscale hybrid cellular automaton simulates large cell populations (up to 10 7 cells) in vitro , while allowing individual cell-cycle progression, and treatment response by modelling radiation-induced mitotic cell death, and immediate cell kill in response to heating. Based on a calibration using a number of experimental growth, cell cycle and survival datasets for HCT116 cells, model predictions agreed well ( R 2 > 0.95) with experimental data within the range of (thermal and radiation) doses tested (0-40 CEM43, 0-5 Gy). The proposed framework offers flexibility for modelling multimodality treatment combinations in different scenarios. It may therefore provide an important step towards the modelling of personalized therapies using a virtual patient tumour., (© 2018 The Author(s).)

Purpose: Firstly, this study provides a real-time implementation of online dose reconstruction for tracked volumetric arc therapy (VMAT). Secondly, this study describes a novel offline quality assurance tool, based on commercial dose calculation algorithms., Methods: Online dose reconstruction for VMAT is a computationally challenging task in terms of computer memory usage and calculation speed. To potentially reduce the amount of memory used, we analyzed the impact of beam angle sampling for dose calculation on the accuracy of the dose distribution. To establish the performance of the method, we planned two single-arc VMAT prostate stereotactic body radiation therapy cases for delivery with dynamic MLC tracking. For quality assurance of our online dose reconstruction method we have also developed a stand-alone offline dose reconstruction tool, which utilizes the RayStation treatment planning system to calculate dose., Results: For the online reconstructed dose distributions of the tracked deliveries, we could establish strong resemblance for 72 and 36 beam co-planar equidistant beam samples with less than 1.2% deviation for the assessed dose-volume indicators (clinical target volume D98 and D2, and rectum D2). We could achieve average runtimes of 28-31 ms per reported MLC aperture for both dose computation and accumulation, meeting our real-time requirement. To cross-validate the offline tool, we have compared the planned dose to the offline reconstructed dose for static deliveries and found excellent agreement (3%/3 mm global gamma passing rates of 99.8%-100%)., Conclusion: Being able to reconstruct dose during delivery enables online quality assurance and online replanning strategies for VMAT. The offline quality assurance tool provides the means to validate novel online dose reconstruction applications using a commercial dose calculation engine., (© 2017 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)