Stereotactic Body Radiotherapy (SBRT) to Localised Prostate Cancer in the Era of MRI-Guided Adaptive Radiotherapy: Doses Delivered in the HERMES Trial Comparing Two- and Five-Fraction Treatments.

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 cm3 was the most exceeded constraint; three patients exceeded the D1 cm3 < 20.8 Gy in the 2-fraction cohort and one patient exceeded the D1 cm3 < 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 cm3, 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.

Magnetic resonance image-guided adaptive radiotherapy enables safe CTV-to-PTV margin reduction in prostate cancer: a cine MRI motion study.

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.

Clinical acceptance and dosimetric impact of automatically delineated elective target and organs at risk for head and neck MR-Linac patients.

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.

Respiratory motion modelling for MR-guided lung cancer radiotherapy: model development and geometric accuracy evaluation.

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 mm3isotropic 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.

Real-time motion-including dose estimation of simulated multi-leaf collimator-tracked magnetic resonance-guided radiotherapy.

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 106 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 PTVDmean , CTVDmean , RectumD2% , and BladderD2% (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.

Interim Toxicity Analysis From the Randomized HERMES Trial of 2- and 5-Fraction Magnetic Resonance Imaging-Guided Adaptive Prostate Radiation Therapy.

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.

Evaluation of non-vendor magnetic resonance imaging sequences for use in bladder cancer magnetic resonance image guided radiotherapy.

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.

An ESTRO-ACROP guideline on quality assurance and medical physics commissioning of online MRI guided radiotherapy systems based on a consensus expert opinion.

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.

Evaluation of therapeutic radiographer contouring for magnetic resonance image guided online adaptive prostate radiotherapy.

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.

Interobserver variation of clinical oncologists compared to therapeutic radiographers (RTT) prostate contours on T2 weighted MRI.

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.

Dosimetric comparison of automatically propagated prostate contours with manually drawn contours in MRI-guided radiotherapy: A step towards a contouring free workflow?

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.

A phase space model of a Versa HD linear accelerator for application to Monte Carlo dose calculation in a real-time adaptive workflow.

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.

Online adaptive radiotherapy for head and neck cancers on the MR linear Accelerator: Introducing a novel modified Adapt-to-Shape approach.

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.

Rapid 4D-MRI reconstruction using a deep radial convolutional neural network: Dracula.

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 mm3) 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.

Machine QA for the Elekta Unity system: A Report from the Elekta MR-linac consortium.

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.

New target volume delineation and PTV strategies to further personalise radiotherapy.

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.

Feasibility of MR-guided ultrahypofractionated radiotherapy in 5, 2 or 1 fractions for prostate cancer.

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.

Daily adaptive radiotherapy for patients with prostate cancer using a high field MR-linac: Initial clinical experiences and assessment of delivered doses compared to a C-arm linac.

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.

Consistent and invertible deformation vector fields for a breathing anthropomorphic phantom: a post-processing framework for the XCAT phantom.

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.

Dosimetric accuracy of delivering SBRT using dynamic arcs on Cyberknife.

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%.