Case report: Cardiac neuroendocrine carcinoma and squamous cell carcinoma treated with MR-guided adaptive stereotactic radiation therapy.

We present two cases of cardiac metastases adjacent to the right ventricle in a 55-year-old male and a 61-year-old female, both treated with magnetic resonance (MR)-guided adaptive stereotactic radiation therapy (SBRT). The prescribed regimen was 30Gy delivered in 3 fractions using a 1.5 Tesla magnetic resonance linear accelerator (MR-linac). Patients exhibited favorable tolerance to the treatment, with no observed acute toxicity.

Personalizing radiotherapy with adaptive radiotherapy: Interest and challenges.

Adaptive radiotherapy (ART) is a recent development in radiotherapy technology and treatment personalization that allows treatment to be tailored to the daily anatomical changes of patients. While it was until recently only performed "offline", i.e. between two radiotherapy sessions, it is now possible during ART to perform a daily online adaptive process for a given patient. Therefore, ART allows a daily customization to ensure optimal coverage of the treatment target volumes with minimized margins, taking into account only the uncertainties related to the adaptive process itself. This optimization appears particularly relevant in case of daily variations in the positioning of the target volume or of the organs at risk (OAR) associated with a proximity of these volumes and a tenuous therapeutic index. ART aims to minimize severe acute and late toxicity and allows tumor dose escalation. These new achievements have been possible thanks to technological development, the contribution of new multimodal and onboard imaging modalities and the integration of artificial intelligence tools for the contouring, planning and delivery of radiation therapy. Online ART is currently available on two types of radiotherapy machines: MR-linear accelerators and recently CBCT-linear accelerators. We will first describe the benefits, advantages, constraints and limitations of each of these two modalities, as well as the online adaptive process itself. We will then evaluate the clinical situations for which online adaptive radiotherapy is particularly indicated on MR- and CBCT-linear accelerators. Finally, we will detail some challenges and possible solutions in the development of online ART in the coming years.

Impact of motion management strategies on abdominal organ at risk delineation for magnetic resonance-guided radiotherapy.

Background and purpose: The impact of respiratory motion management strategies for abdominal radiotherapy, such as abdominal compression (AC) and breath hold (BH), on abdominal organ at risk (OAR) delineation on magnetic resonance imaging (MRI) is unknown. This feasibility study compared the inter- and intra- observer delineation variation on MRI acquired with AC, BH for three critical abdominal OAR. Materials and methods: T2-weighted (W) 3D MRI in free-breathing (FB) and with AC, and T1W 3D mDixon exhale BH were acquired. Four observers blinded to motion management strategy used, delineated stomach, liver, and duodenum on all MRI. One case per strategy was repeated over 6 weeks later to quantify intra-observer variation. Simultaneous truth and performance level estimation (STAPLE) contours for each OAR were generated, median and IQR mean distance to agreement (mDTA) and maximum Hausdorff distance (HD) between observer and STAPLE contours were calculated. Observers scored organ visibility on each MRI using a four-point Likert scale. Results: A total of 27 scans including repeats were delineated. Pooled mDTA for all OARs was 1.3 mm (0.5 mm) with AC, 1.4 mm (1.0 mm) with BH, and 1.3 mm (0.5 mm) in FB. Intra-observer mDTA was highest for all organs in FB with 10.8 mm for duodenum, 1.8 mm for liver, and 2.7 mm for stomach. The pooled mean perceptual quality score value was highest for AC across organs. Conclusions: No motion management strategy demonstrated superior similarity across OAR, emphasizing the need for personalised approaches based on individual clinical and patient factors.

Clinical Outcomes of Prostate SBRT Using Non-adaptive MR-Guided Radiotherapy.

OBJECTIVES: Stereotactic body radiotherapy (SBRT) is widely used for localized prostate cancer and implementation of MR-guided radiotherapy has the advantage of tighter margins and improved sparing of organs at risk. Here we evaluate outcomes and time required to treat using non-adaptive MR-guided SBRT (MRgSBRT) for localized prostate cancer at our institution. METHODS: From 9/2019 to 11/2021 we conducted a retrospective review of 80 consecutive patients who were treated with MRgSBRT to the prostate. Patients included low (LR) (5%), favorable intermediate (FIR) (40%), unfavorable intermediate (UIR) (49%), and high risk (HR) (6%). Short-term androgen deprivation therapy was used in 32% of patients. Target volumes included prostate gland and proximal seminal vesicles with an isotropic 3 mm margin. Treatment was prescribed to 36.25 Gy in 5 fractions every other day with urethral sparing. Hydrogel spacer was used in 18% of patients. Time on the linac was recorded as beam on time (BOT) plus total treatment time (TTT) including gating. Analyzed outcomes included PSA response and patient reported outcomes scored by the American Urological Association (AUA) questionnaire and toxicity per CTCAE v5. General linear regression model was used to analyze factors affecting PSA and AUA in longitudinal follow up, and chi-square test was used to assess factors affecting toxicity. RESULTS: Median follow up was 19.3 months (3.8 - 36.6). Median BOT was 4.6 min (2.6 - 7.2) with a median TTT of 11 min (7.6 - 15.8). Pre-treatment vs post-RT median PSA was 6.36 (2.20 - 19.6) vs 0.85 (0.19 - 3.6), respectively (P < 0.001). PSA decrease differed significantly when patients were stratified by risk category, favoring LR/FIR vs UIF/HR group (P = 0.019). Four (5%) patients experienced a biochemical failure (BCF), with a median time to BCF of 20.4 months (7.9 - 34.5). Median biochemical failure free survival (BCFFS) was not reached, with 2-yr and 4-yr BCFFS of 97.1% and 72.1%, respectively. Patients with LR/FIR disease had 100% 2-yr and 4-yr BCFFS, whereas patients with UIF/HR had 95% and 41% 2-yr and 4-yr BCFFS (P = 0.05). Mean pre-treatment AUA was 7.3 (1 - 25) vs 11.3 (1 - 26) at first follow-up; however, AUA normalized to baseline over time. Urethral Dmax ≥35 Gy trended to lower AUA score at all follow-ups (P = 0.07). Forty-one (51%) patients reported grade 1-2 genitourinary toxicities at the 1 month follow up. Grade 3 toxicity (proctitis) was noted in 1 patient. There was no decrease in any grade rectal toxicity with use of hydrogel spacer (3 vs 6, P = 0.2). No grade ≥4 toxicities was observed. CONCLUSIONS: MRgSBRT has the potential for treatment adaptation but this comes at the cost of increased resource utilization. Our experience with non-adaptive MRgSBRT of the prostate highlights its short treatment times as well as efficacy with good PSA control and low toxicity profile.

Does a peer review group consensus process for MR-Linac patients affect clinical care? Evaluation of impact and feasibility.

Background and purpose: Peer review is an important component of quality assurance in radiotherapy. To our knowledge, there are no studies reporting on the feasibility and outcomes of the peer review process for magnetic resonance (MR) guided radiotherapy (MRgRT) on the MR linear accelerator (MR-Linac) despite the planning complexity involved and its evolving clinical indications. This study aimed to quantify the rate of change in treatment plans post-peer review and the time and resources required. Materials and methods: Fifty-five cases presented at weekly MR-Linac peer review meetings across two centres from 8 June to 21 September 2023 were prospectively collected. Cases were analysed to determine the rate and extent of plan changes based on the Peer Review Audit Tool for radiation oncology (PRAT) developed by the Royal Australian and New Zealand College of Radiologists (RANZCR). Results: Peer review resulted in changes to 36.4 % of treatment plans (n = 20), with 3.6 % (n = 2) having major changes requiring deferment of treatment. The most frequent changes were to organs at risk (OAR) volumes involving both delineation and increased OAR sparing (16.4 %, n = 9), total dose and fractionation (10.9 %, n = 6) and target volume dose coverage (5.5 %, n = 3). Patients with SBRT plans (39.1 % cf 22.2 %), oligometastatic/oligoprogressive sites (38.1 % cf 30.7 %) and reirradiation cases (41.2 % cf 34.2 %) had higher rates of change. Cases took a mean of 7 min (range 2-15 minutes) to discuss. Conclusion: The high rates of plan changes support the value of peer review in MRgRT. We recommend, where possible that all MRgRT cases, particularly those involving SBRT plans, oligometastatic/oligoprogressive sites, and/or reirradiation, be subject to peer review.

Robustness of radiomics features on 0.35 T magnetic resonance imaging for magnetic resonance-guided radiotherapy.

Background and purpose: MR-guided radiotherapy adds the precision of magnetic resonance imaging (MRI) to the therapeutic benefits of a linear accelerator. Prior to each therapeutic session, an MRI generates a significant volume of imaging data ripe for analysis. Radiomics stands at the forefront of medical imaging and oncology research, dedicated to mining quantitative imaging attributes to forge predictive models. However, the robustness of these models is often challenged. Materials and methods: To assess the robustness of feature extraction, we conducted reproducibility studies using a 0.35 T MR-linac system, employing both a specialized phantom and patient-derived images, focusing on cases of pancreatic cancer. We extracted shape-based, first-order and textural features from patient-derived images and only first-order and textural features from phantom-derived images. The impact of the delay between simulation and first fraction images was also assessed with an equivalence test. Results: From 107 features evaluated, 58 (54 %) were considered as non-reproducible: 18 were uniformly inconsistent across both phantom and patient images, 9 were specific to phantom-based analysis, and 31 to patient-derived data. Conclusion: Our findings show that a significant proportion of radiomic features extracted from this dual dataset were unreliable. It is essential to discard these non-reproducible elements to refine and enhance radiomic model development, particularly for MR-guided radiotherapy in pancreatic cancer.

Impact of 1.5†T Magnetic Field on Treatment Plan Quality in MR-Guided Radiotherapy: Typical Phantom Test Cases.

PURPOSE: This study aims to investigate the influence of the magnetic field on treatment plan quality using typical phantom test cases, which encompass a circle target test case, AAPM TG119 test cases (prostate, head-and-neck, C-shape, multi-target test cases), and a lung test case. MATERIALS AND METHODS: For the typical phantom test cases, two plans were formulated. The first plan underwent optimization in the presence of a 1.5 Tesla magnetic field (1.5 T plan). The second plan was re-optimized without a magnetic field (0 T plan), utilizing the same optimization conditions as the first plan. The two plans were compared based on various parameters, including con-formity index (CI), homogeneity index (HI), fit index (FI) and dose coverage of the planning target volume (PTV), dose delivered to organs at risk (OARs) and normal tissue (NT), monitor unit (MU). A plan-quality metric (PQM) scoring procedure was employed. For the 1.5 T plans, dose verifications were performed using an MR-compatible ArcCHECK phantom. RESULTS: A smaller dose influence of the magnetic field was found for the circle target, prostate, head-and-neck, and C-shape test cases, compared with the multi-target and lung test cases. In the multi-target test case, the significant dose influence was on the inferior PTV, followed by the superior PTV. There was a relatively large dose influence on the PTV and OARs for lung test case. No statistically significant differences in PQM and MUs were observed. For the 1.5 T plans, gamma passing rates were all higher than 95% with criteria of 2 mm/3% and 2 mm/2%. CONCLUSION: The presence of a 1.5 T magnetic field had a relatively large impact on dose parameters in the multi-target and lung test cases compared with other test cases. However, there were no significant influences on the plan-quality metric, MU and dose accuracy for all test cases.

Investigating the use of comprehensive motion monitoring for intrafraction 3D drift assessment of hypofractionated prostate cancer patients on a 1.5T magnetic resonance imaging radiotherapy system.

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

Abdominal MR Multitasking for radiotherapy treatment planning: A motion-resolved and multicontrast 3D imaging approach.

PURPOSE: Radiotherapy treatment planning (RTP) using MR has been used increasingly for the abdominal site. Multiple contrast weightings and motion-resolved imaging are desired for accurate delineation of the target and various organs-at-risk and patient-tailored planning. Current MR protocols achieve these through multiple scans with distinct contrast and variable respiratory motion management strategies and acquisition parameters, leading to a complex and inaccurate planning process. This study presents a standalone MR Multitasking (MT)-based technique to produce volumetric, motion-resolved, multicontrast images for abdominal radiotherapy treatment planning. METHODS: The MT technique resolves motion and provides a wide range of contrast weightings by repeating a magnetization-prepared (saturation recovery and T2 preparations) spoiled gradient-echo readout series and adopting the MT image reconstruction framework. The performance of the technique was assessed through digital phantom simulations and in vivo studies of both healthy volunteers and patients with liver tumors. RESULTS: In the digital phantom study, the MT technique presented structural details and motion in excellent agreement with the digital ground truth. The in vivo studies showed that the motion range was highly correlated (R2 = 0.82) between MT and 2D cine imaging. MT allowed for a flexible contrast-weighting selection for better visualization. Initial clinical testing with interobserver analysis demonstrated acceptable target delineation quality (Dice coefficient = 0.85 ± 0.05, Hausdorff distance = 3.3 ± 0.72 mm). CONCLUSION: The developed MT-based, abdomen-dedicated technique is capable of providing motion-resolved, multicontrast volumetric images in a single scan, which may facilitate abdominal radiotherapy treatment planning.

Carbon ion beam dosimetry in magnetic fields using Farmer-type ionization chambers of different radii: measurements and simulations.

Objective.To investigate magnetic field effects on the dose distribution and ionization chambers response in carbon ion reference fields and determine magnetic field correction factors for chambers of different volumes.Approach.The response of six Farmer-type chambers with varying radii (1-6 mm, termed as R1-R6) was measured in magnetic fields up to 1 T in 0.1 T increments using an experimental electromagnet and compared with Monte Carlo simulations. Chamber readings were measured in the entrance region of a monoenergetic carbon ion beam of 390.75 MeV u-1. A lower energy of 200.28 MeV u-1was applied to chamber R3 for comparison. Polarity and recombination corrections were investigated for the R3 chamber. The local dose change induced by the magnetic field was calculated by Monte Carlo, which together with change of the chamber's response, was used to calculate the final magnetic field correction factors.Main results.The dependence of the chamber response on the magnetic field was non-linear and volume-dependent. Maximum changes ranged from 0.30% (R4) to 0.62% (R5) at 0.2 T. For R3, the response for the lower energy was systematically decreased by 0.2% in the range of 0.2 T to 0.7 T. No significant effect of the magnetic field on polarity and ion recombination correction was found. The maximum variation of the local dose was found to be (0.03 ± 0.08) % at 0.2 T for beam energy of 390.75 MeV u-1. Magnetic field correction factors for the different chambers ranged from 0.28% (R4) to 0.60% (R5).Significance.This study provides the first detailed analysis of chambers' response to magnetic flux densities of up to 1 T using chambers of different radii and comparison with simulations. By combining the chamber response alterations with local dose changes magnetic field correction factors were calculated for all six chambers, including the commercial Farmer-type chamber.

Clinical Outcomes of Online Adaptive Magnetic Resonance-Guided Stereotactic Body Radiotherapy of Adrenal Metastases from a Single Institution.

(1) Background: Recent publications foster stereotactic body radiotherapy (SBRT) in patients with adrenal oligometastases or oligoprogression. However, local control (LC) after non-adaptive SBRT shows the potential for improvement. Online adaptive MR-guided SBRT (MRgSBRT) improves tumor coverage and organ-at-risk (OAR) sparing. Long-term results of adaptive MRgSBRT are still sparse. (2) Methods: Adaptive MRgSBRT was performed on a 0.35 T MR-Linac. LC, overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity were assessed. (3) Results: 35 patients with 40 adrenal metastases were analyzed. The median gross tumor volume was 30.6 cc. The most common regimen was 10 fractions at 5 Gy. The median biologically effective dose (BED10) was 75.0 Gy. Plan adaptation was performed in 98% of all fractions. The median follow-up was 7.9 months. One local failure occurred after 16.6 months, resulting in estimated LC rates of 100% at one year and 90% at two years. ORR was 67.5%. The median OS was 22.4 months, and the median PFS was 5.1 months. No toxicity > CTCAE grade 2 occurred. (4) Conclusions: LC and ORR after adrenal adaptive MRgSBRT were excellent, even in a cohort with comparably large metastases. A BED10 of 75 Gy seems sufficient for improved LC in comparison to non-adaptive SBRT.

A multi-institutional comparison of retrospective deformable dose accumulation for online adaptive magnetic resonance-guided radiotherapy.

Background and Purpose: Application of different deformable dose accumulation (DDA) solutions makes institutional comparisons after online-adaptive magnetic resonance-guided radiotherapy (OA-MRgRT) challenging. The aim of this multi-institutional study was to analyze accuracy and agreement of DDA-implementations in OA-MRgRT. Material and Methods: One gold standard (GS) case deformed with a biomechanical-model and five clinical cases consisting of prostate (2x), cervix, liver, and lymph node cancer, treated with OA-MRgRT, were analyzed. Six centers conducted DDA using institutional implementations. Deformable image registration (DIR) and DDA results were compared using the contour metrics Dice Similarity Coefficient (DSC), surface-DSC, Hausdorff-distance (HD95%), and accumulated dose-volume histograms (DVHs) analyzed via intraclass correlation coefficient (ICC) and clinical dosimetric criteria (CDC). Results: For the GS, median DDA errors ranged from 0.0 to 2.8 Gy across contours and implementations. DIR of clinical cases resulted in DSC > 0.8 for up to 81.3% of contours and a variability of surface-DSC values depending on the implementation. Maximum HD95%=73.3 mm was found for duodenum in the liver case. Although DVH ICC > 0.90 was found after DDA for all but two contours, relevant absolute CDC differences were observed in clinical cases: Prostate I/II showed maximum differences in bladder V28Gy (10.2/7.6%), while for cervix, liver, and lymph node the highest differences were found for rectum D2cm3 (2.8 Gy), duodenum Dmax (7.1 Gy), and rectum D0.5cm3 (4.6 Gy). Conclusion: Overall, high agreement was found between the different DIR and DDA implementations. Case- and algorithm-dependent differences were observed, leading to potentially clinically relevant results. Larger studies are needed to define future DDA-guidelines.

Pixelwise Gradient Model for Image Fusion (PGMIF): a multi-sequence magnetic resonance imaging (MRI) fusion model for tumor contrast enhancement of nasopharyngeal carcinoma.

Background: Different image modalities capture different aspects of a patient. It is desirable to produce images that capture all such features in a single image. This research investigates the potential of multi-modal image fusion method to enhance magnetic resonance imaging (MRI) tumor contrast and its consistency across different patients, which can capture both the anatomical structures and tumor contrast clearly in one image, making MRI-based target delineation more accurate and efficient. Methods: T1-weighted (T1-w) and T2-weighted (T2-w) magnetic resonance (MR) images from 80 nasopharyngeal carcinoma (NPC) patients were used. A novel image fusion method, Pixelwise Gradient Model for Image Fusion (PGMIF), which is based on the pixelwise gradient to capture the shape and a generative adversarial network (GAN) term to capture the image contrast, was introduced. PGMIF is compared with several popular fusion methods. The performance of fusion methods was quantified using two metrics: the tumor contrast-to-noise ratio (CNR), which aims to measure the contrast of the edges, and a Generalized Sobel Operator Analysis, which aims to measure the sharpness of edge. Results: The PGMIF method yielded the highest CNR [median (mdn) =1.208, interquartile range (IQR) =1.175-1.381]. It was a statistically significant enhancement compared to both T1-w (mdn =1.044, IQR =0.957-1.042, P<5.60×10-4) and T2-w MR images (mdn =1.111, IQR =1.023-1.182, P<2.40×10-3), and outperformed other fusion models: Gradient Model with Maximum Comparison among Images (GMMCI) (mdn =0.967, IQR =0.795-0.982, P<5.60×10-4), Deep Learning Model with Weighted Loss (DLMWL) (mdn =0.883, IQR =0.832-0.943, P<5.60×10-4), Pixelwise Weighted Average (PWA) (mdn =0.875, IQR =0.806-0.972, P<5.60×10-4) and Maximum of Images (MoI) (mdn =0.863, IQR =0.823-0.991, P<5.60×10-4). In terms of the Generalized Sobel Operator Analysis, a measure based on Sobel operator to measure contrast enhancement, PGMIF again exhibited the highest Generalized Sobel Operator (mdn =0.594, IQR =0.579-0.607; mdn =0.692, IQR =0.651-0.718 for comparison with T1-w and T2-w images), compared to: GMMCI (mdn =0.491, IQR =0.458-0.507, P<5.60×10-4; mdn =0.495, IQR =0.487-0.533, P<5.60×10-4), DLMWL (mdn =0.292, IQR =0.248-0.317, P<5.60×10-4; mdn =0.191, IQR =0.179-0.243, P<5.60×10-4), PWA (mdn =0.423, IQR =0.383-0.455, P<5.60×10-4; mdn =0.448, IQR =0.414-0.463, P<5.60×10-4) and MoI (mdn =0.437, IQR =0.406-0.479, P<5.60×10-4; mdn =0.540, IQR =0.521-0.636, P<5.60×10-4), demonstrating superior contrast enhancement and sharpness compared to other methods. Conclusions: Based on the tumor CNR and Generalized Sobel Operator Analysis, the proposed PGMIF method demonstrated its capability of enhancing MRI tumor contrast while keeping the anatomical structures of the input images. It holds promises for NPC tumor delineation in radiotherapy.

Skin dose investigations on a 0.5 T parallel rotating biplanar linac-MR using Monte Carlo simulations and measurements.

BACKGROUND: The Alberta rotating biplanar linac-MR has a 0.5 T magnetic field parallel to the beamline. When developing a new linac-MR system, interactions of charged particles with the magnetic field necessitate careful consideration of skin dose and tissue interface effects. PURPOSE: To investigate the effect of the magnetic field on skin dose using measurements and Monte Carlo (MC) simulations. METHODS: We develop an MC model of our linac-MR, which we validate by comparison with ion chamber measurements in a water tank. Additionally, MC simulation results are compared with radiochromic film surface dose measurements on solid water. Variations in surface dose as a function of field size are measured using a parallel plate ion chamber in solid water. Using an anthropomorphic computational phantom with a 2 mm-thick skin layer, we investigate dose distributions resulting from three beam arrangements. Magnetic field on and off scenarios are considered for all measurements and simulations. RESULTS: For a 20 × 20 cm2 field size, D 0.2 c c ${D_{0.2cc}}$ (the minimum dose to the hottest contiguous 0.2 cc volume) for the top 2 mm of a simple water phantom is 72% when the magnetic field is on, compared to 34% with magnetic field off (values are normalized to the central axis dose maximum). Parallel plate ion chamber measurements demonstrate that the relative increase in surface dose due to the magnetic field decreases with increasing field size. For the anthropomorphic phantom, D ∼ 0.2 c c ${D_{ \sim 0.2cc}}$ (minimum skin dose in the hottest 1 × 1 × 1 cm3 cube) shows relative increases of 20%-28% when the magnetic field is on compared to when it is off. With magnetic field off, skin D ∼ 0.2 c c ${D_{ \sim 0.2cc}}$ is 71%, 56%, and 21% for medial-lateral tangents, anterior-posterior beams, and a five-field arrangement, respectively. For magnetic field on, the corresponding skin D ∼ 0.2 c c ${D_{ \sim 0.2cc}}$ values are 91%, 67%, and 25%. CONCLUSIONS: Using a validated MC model of our linac-MR, surface doses are calculated in various scenarios. MC-calculated skin dose varies depending on field sizes, obliquity, and the number of beams. In general, the parallel linac-MR arrangement results in skin dose enhancement due to charged particles spiraling along magnetic field lines, which impedes lateral motion away from the central axis. Nonetheless, considering the results presented herein, treatment plans can be designed to minimize skin dose by, for example, avoiding oblique beams and using a larger number of fields.

Compliance of volunteers in a fully-enclosed patient rotation system for MR-guided radiation therapy: a prospective study.

BACKGROUND: Particle therapy makes a noteworthy contribution in the treatment of tumor diseases. In order to be able to irradiate from different angles, usually expensive, complex and large gantries are used. Instead rotating the beam via a gantry, the patient itself might be rotated. Here we present tolerance and compliance of volunteers for a fully-enclosed patient rotation system in a clinical magnetic resonance (MR)-scanner for potential use in MR-guided radiotherapy, conducted within a prospective evaluation study. METHODS: A patient rotation system was used to simulate and perform magnetic resonance imaging (MRI)-examinations with 50 volunteers without an oncological question. For 20 participants, the MR-examination within the bore was simulated by introducing realistic MRI noise, whereas 30 participants received an examination with image acquisition. Initially, body parameters and claustrophobia were assessed. The subjects were then rotated to different angles for simulation (0°, 45°, 90°, 180°) and imaging (0°, 70°, 90°, 110°). At each angle, anxiety and motion sickness were assessed using a 6-item State-Trait-Anxiety-Inventory (STAI-6) and a modified Motion Sickness Assessment Questionnaire (MSAQ). In addition, general areas of discomfort were evaluated. RESULTS: Out of 50 subjects, three (6%) subjects terminated the study prematurely. One subject dropped out during simulation due to nausea while rotating to 45°. During imaging, further two subjects dropped out due to shoulder pain from positioning at 90° and 110°, respectively. The average result for claustrophobia (0 = no claustrophobia to 4 = extreme claustrophobia) was none to light claustrophobia (average score: simulation 0.64 ± 0.33, imaging 0.51 ± 0.39). The mean anxiety scores (0% = no anxiety to 100% = maximal anxiety) were 11.04% (simulation) and 15.82% (imaging). Mean motion sickness scores (0% = no motion sickness to 100% = maximal motion sickness) of 3.5% (simulation) and 6.76% (imaging) were obtained across all participants. CONCLUSION: Our study proves the feasibility of horizontal rotation in a fully-enclosed rotation system within an MR-scanner. Anxiety scores were low and motion sickness was only a minor influence. Both anxiety and motion sickness showed no angular dependency. Further optimizations with regard to immobilization in the rotation device may increase subject comfort.

Adaptive MRI-guided stereotactic body radiation therapy for locally advanced pancreatic cancer - A phase II study.

PURPOSE: Stereotactic body radiotherapy (SBRT) has emerged as a promising new modality for locally advanced pancreatic cancer (LAPC). The current study evaluated the efficacy and toxicity of SBRT in patients with LAPC (NCT03648632). METHODS: This prospective single institution phase II study recruited patients with histologically or cytologically proven adenocarcinoma of the pancreas after more than two months of combination chemotherapy with no sign of progressive disease. Patients were prescribed 50-60 Gy in 5-8 fractions. Patients were initially treated on a standard linac (n = 4). Since 2019, patients were treated using online magnetic resonance (MR) image-guidance on a 1.5 T MRI-linac, where the treatment plan was adapted to the anatomy of the day. The primary endpoint was resection rate. RESULTS: Twenty-eight patients were enrolled between August 2018 and March 2022. All patients had non-resectable disease at time of diagnosis. Median follow-up from inclusion was 28.3 months (95 % CI 24.0-NR). Median progression-free and overall survival from inclusion were 7.8 months (95 % CI 5.0-14.8) and 16.5 months (95 % CI 10.7-22.6), respectively. Six patients experienced grade III treatment-related adverse events (jaundice, nausea, vomiting and/or constipation). One of the initial four patients receiving treatment on a standard linac experienced a grade IV perforation of the duodenum. Six patients (21 %) underwent resection. A further one patient was offered resection but declined. CONCLUSION: This study demonstrates that SBRT in patients with LAPC was associated with promising overall survival and resection rates. Furthermore, SBRT was safe and well tolerated, with limited severe toxicities.

Treatment planning evaluation and experimental validation of the magnetic resonance-based intrafraction drift correction.

Background and purpose: MRI-guided online adaptive treatments can account for interfractional variations, however intrafraction motion reduces treatment accuracy. Intrafraction plan adaptation methods, such as the Intrafraction Drift Correction (IDC) or sub-fractionation, are needed. IDC uses real-time automatic monitoring of the tumor position to initiate plan adaptations by repositioning segments. IDC is a fast adaptation method that occurs only when necessary and this method could enable margin reduction. This research provides a treatment planning evaluation and experimental validation of the IDC. Materials and methods: An in silico treatment planning evaluation was performed for 13 prostate patients mid-treatment without and with intrafraction plan adaptation (IDC and sub-fractionation). The adaptation methods were evaluated using dose volume histogram (DVH) metrics. To experimentally verify IDC a treatment was mimicked whereby a motion phantom containing an EBT3 film moved mid-treatment, followed by repositioning of segments. In addition, the delivered treatment was irradiated on a diode array phantom for plan quality assurance purposes. Results: The planning study showed benefits for using intrafraction adaptation methods relative to no adaptation, where the IDC and sub-fractionation showed consistently improved target coverage with median target coverages of 100.0%. The experimental results verified the IDC with high minimum gamma passing rates of 99.1% and small mean dose deviations of maximum 0.3%. Conclusion: The straightforward and fast IDC technique showed DVH metrics consistent with the sub-fractionation method using segment weight re-optimization for prostate patients. The dosimetric and geometric accuracy was shown for a full IDC workflow using film and diode array dosimetry.

Inter-scanner super-resolution of 3D cine MRI using a transfer-learning network for MRgRT.

Objective. Deep-learning networks for super-resolution (SR) reconstruction enhance the spatial-resolution of 3D magnetic resonance imaging (MRI) for MR-guided radiotherapy (MRgRT). However, variations between MRI scanners and patients impact the quality of SR for real-time 3D low-resolution (LR) cine MRI. In this study, we present a personalized super-resolution (psSR) network that incorporates transfer-learning to overcome the challenges in inter-scanner SR of 3D cine MRI.Approach: Development of the proposed psSR network comprises two-stages: (1) a cohort-specific SR (csSR) network using clinical patient datasets, and (2) a psSR network using transfer-learning to target datasets. The csSR network was developed by training on breath-hold and respiratory-gated high-resolution (HR) 3D MRIs and their k-space down-sampled LR MRIs from 53 thoracoabdominal patients scanned at 1.5 T. The psSR network was developed through transfer-learning to retrain the csSR network using a single breath-hold HR MRI and a corresponding 3D cine MRI from 5 healthy volunteers scanned at 0.55 T. Image quality was evaluated using the peak-signal-noise-ratio (PSNR) and the structure-similarity-index-measure (SSIM). The clinical feasibility was assessed by liver contouring on the psSR MRI using an auto-segmentation network and quantified using the dice-similarity-coefficient (DSC).Results. Mean PSNR and SSIM values of psSR MRIs were increased by 57.2% (13.8-21.7) and 94.7% (0.38-0.74) compared to cine MRIs, with the reference 0.55 T breath-hold HR MRI. In the contour evaluation, DSC was increased by 15% (0.79-0.91). Average time consumed for transfer-learning was 90 s, psSR was 4.51 ms per volume, and auto-segmentation was 210 ms, respectively.Significance. The proposed psSR reconstruction substantially increased image and segmentation quality of cine MRI in an average of 215 ms across the scanners and patients with less than 2 min of prerequisite transfer-learning. This approach would be effective in overcoming cohort- and scanner-dependency of deep-learning for MRgRT.

Stereotactic ultrahypofractionated MR-guided radiotherapy for localized prostate cancer - Acute toxicity and patient-reported outcomes in the prospective, multicenter SMILE phase II trial.

Background: Due to superior image quality and daily adaptive planning, MR-guided stereotactic body radiation therapy (MRgSBRT) has the potential to further widen the therapeutic window in radiotherapy of localized prostate cancer. This study reports on acute toxicity rates and patient-reported outcomes after MR-guided adaptive ultrahypofractionated radiotherapy for localized prostate cancer within the prospective, multicenter phase II SMILE trial. Materials and methods: A total of 69 patients with localized prostate cancer underwent MRgSBRT with daily online plan adaptation. Inclusion criteria comprised a tumor stage ≤ T3a, serum PSA value ≤ 20 ng/ml, ISUP Grade group ≤ 4. A dose of 37.5 Gy was prescribed to the PTV in five fractions on alternating days with an optional simultaneous boost of 40 Gy to the dominant intraprostatic lesion defined by multiparametric MRI. Acute genitourinary (GU-) and gastrointestinal (GI-) toxicity, as defined by CTCAE v. 5.0 and RTOG as well as patient-reported outcomes according to EORTC QLQ-C30 and -PR25 scores were analyzed at completion of radiotherapy, 6 and 12 weeks after radiotherapy and compared to baseline symptoms. Results: There were no toxicity-related treatment discontinuations. At the 12-week follow-up visit, no grade 3 + toxicities were reported according to CTCAE. Up until the 12-week visit, in total 16 patients (23 %) experienced a grade 2 GU or GI toxicity. Toxicity rates peaked at the end of radiation therapy and subsided within the 12-week follow-up period. At the 12-week follow-up visit, no residual grade 2 GU toxicities were reported and 1 patient (1 %) had residual grade 2 enteritic symptoms. With exception to a significant improvement in the emotional functioning score following MRgSBRT, no clinically meaningful changes in the global health status nor in relevant subscores were reported. Conclusion: Daily online-adaptive MRgSBRT for localized prostate cancer resulted in an excellent overall toxicity profile without any major negative impact on quality of life.

Characterization of spatial integrity with active and passive implants in a low-field magnetic resonance linear accelerator scanner.

Background and Purpose: Standard imaging protocols can guarantee the spatial integrity of magnetic resonance (MR) images utilized in radiotherapy. However, the presence of metallic implants can significantly compromise this integrity. Our proposed method aims at characterizing the geometric distortions induced by both passive and active implants commonly encountered in planning images obtained from a low-field 0.35 T MR-linear accelerator (LINAC). Materials and Methods: We designed a spatial integrity phantom defining 1276 control points and covering a field of view of 20x20x20 cm3. This phantom was scanned in a water tank with and without different implants used in hip and shoulder arthroplasty procedures as well as with active cardiac stimulators. The images were acquired with the clinical planning sequence (balanced steady-state free-precession, resolution 1.5x1.5x1.5 mm3). Spatial integrity was assessed by the Euclidian distance between the control point detected on the image and their theoretical locations. A first plane free of artefact (FPFA) was defined to evaluate the spatial integrity beyond the larger banding artefact. Results: In the region extending up to 20 mm from the largest banding artefacts, the tested passive and active implants could cause distortions up to 2 mm and 3 mm, respectively. Beyond this region the spatial integrity was recovered and the image could be considered as unaffected by the implants. Conclusions: We characterized the impact of common implants on a low field MR-LINAC planning sequence. These measurements could support the creation of extra margin while contouring organs at risk and target volumes in the vicinity of implants.