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Radiotherapy, a crucial technique in cancer therapy, has traditionally relied on the premise of largely unchanging patient anatomy during the treatment course and encompassing uncertainties by target margins. This review introduces adaptive radiotherapy (ART), a notable innovation that addresses anatomy changes and optimizes the therapeutic ratio. ART utilizes advanced imaging techniques such as CT, MRI, and PET to modify the treatment plan based on observed anatomical changes and even biological changes during the course of treatment. The narrative review provides a comprehensive guide on ART for healthcare professionals and trainees in radiation oncology and anyone else interested in the topic. The incorporation of artificial intelligence in ART has played a crucial role in improving effectiveness, particularly in contour segmentation, treatment planning, and quality assurance. This has expedited the process to render online ART feasible, lowered the burden for radiation oncology practitioners, and enhanced the precision of dynamically personalized treatment. Current technical and clinical progress on ART is discussed in this review, highlighting the ongoing development of imaging technologies and AI and emphasizing their contribution to enhancing the applicability and effectiveness of ART.

Simple Summary: The MR-Linac (or MRL) is a powerful new device that integrates high-resolution magnetic resonance imaging (MRI) within a linear accelerator to enhance the precision of radiation treatment delivery beyond the predominantly CT-guided standard of care. Our institution was one of the seven founding members of the consortium that tested and refined the 1.5 Tesla MR-Linac in preparation for the first-in-human clinical trials, resulting in several years of early clinical experience. Its application in delivering ablative doses (stereotactic ablative radiation therapy; SBRT) to renal cell carcinoma (RCC) or upper tract urothelial carcinomas (UTUC) has been of particular interest out of clinical necessity and technical challenge. We present a retrospective analysis of our multi-year experience using MRL-SBRT, with emphasis on our evolving treatment setup and early clinical outcomes. Our aim is to contribute to and support the development and innovation of further programs using one of the largest worldwide single-institution cohorts. Background/Objectives: Advancements in radiotherapy technology now enable the delivery of ablative doses to targets in the upper urinary tract, including primary renal cell carcinoma (RCC) or upper tract urothelial carcinomas (UTUC), and secondary involvement by other histologies. Magnetic resonance imaging-guided linear accelerators (MR-Linacs) have shown promise to further improve the precision and adaptability of stereotactic body radiotherapy (SBRT). Methods: This single-institution retrospective study analyzed 34 patients (31 with upper urinary tract non-metastatic primaries [RCC or UTUC] and 3 with metastases of non-genitourinary histology) who received SBRT from August 2020 through September 2024 using a 1.5 Tesla MR-Linac system. Treatment plans were adjusted by using [online settings] for "adapt-to-position" (ATP) and "adapt-to-shape" (ATS) strategies for anatomic changes that developed during treatment; compression belts were used for motion management. Results: The median duration of treatment was 56 min overall and was significantly shorter using the adapt-to-position (ATP) (median 54 min, range 38–97 min) in comparison with adapt-to-shape (ATS) option (median 80, range 53–235 min). Most patients (77%) experienced self-resolving grade 1–2 acute radiation-induced toxicity; none had grade ≥ 3. Three participants (9%) experienced late grade 1–2 toxicity, potentially attributable to SBRT, with one (3%) experiencing grade 3. Conclusions: We conclude that MR-Linac-based SBRT, supported by online plan adaptation, is a feasible, safe, and highly precise treatment modality for the definitive management of select upper urinary tract lesions. [ABSTRACT FROM AUTHOR]

Variability in the target and organs at risk (OARs) in cervical cancer treatment presents challenges for precise radiotherapy. Adaptive radiotherapy (ART) offers the potential to enhance treatment precision and outcomes. However, the increased workload and a lack of consensus on the most suitable ART approach hinder its clinical adoption. This systematic review aims to assess the current use of adaptive strategies for cervical cancer and define the optimal approach. A systematic review of current literature published between January 2012 and May 2023 was conducted. Searches used PubMed/Medline, Cochrane Library, and Web of Science databases, supplemented with the University of Manchester, Google Scholar, and papers retrieved from reference lists. The review assessed workflows, compared dosimetric benefits, and examined resources for each identified strategy. Excluded were abstracts, conference abstracts, reviews, articles unrelated to ART management, proton therapy, brachytherapy, or qualitative studies. A narrative synthesis involved data tabulation, summarizing selected studies detailing workflow for cervical cancer and dosimetric outcomes for targets and OARs. Sixteen articles met the inclusion criteria; these were mostly retrospective simulation planning studies, except four studies that had been clinically implemented. We identified five approaches for ART radiotherapy for cervical cancer: reactive and scheduled adaptation, internal target volume (ITV)-based approach using library of plans (LOP), fixed-margin approach using LOP, and real-time adaptation, with each approach reducing irradiated volumes without compromising target coverage compared to the non-ART approach. The LOP-based ITV approach is the most used and clinically assessed. Identifying the optimal strategy is challenging due to dosimetric assessment limitations. Implementing cervical cancer ART necessitates strategic optimization of clinical benefits and resources through research, including studies to identify the optimal frequency, and prospective evaluations of toxicity. [ABSTRACT FROM AUTHOR]

Background: Cardiac applications in radiation therapy are rapidly expanding including magnetic resonance guided radiation therapy (MRgRT) for real‐time gating for targeting and avoidance near the heart or treating ventricular tachycardia (VT). Purpose: This work describes the development and implementation of a novel multi‐modality and magnetic resonance (MR)‐compatible cardiac phantom. Methods: The patient‐informed 3D model was derived from manual contouring of a contrast‐enhanced Coronary Computed Tomography Angiography scan, exported as a Stereolithography model, then post‐processed to simulate female heart with an average volume. The model was 3D‐printed using Elastic50A to provide MR contrast to water background. Two rigid acrylic modules containing cardiac structures were designed and assembled, retrofitting to an MR‐safe programmable motor to supply cardiac and respiratory motion in superior‐inferior directions. One module contained a cavity for an ion chamber (IC), and the other was equipped with multiple interchangeable cavities for plastic scintillation detectors (PSDs). Images were acquired on a 0.35 T MR‐linac for validation of phantom geometry, motion, and simulated online treatment planning and delivery. Three motion profiles were prescribed: patient‐derived cardiac (sine waveform, 4.3 mm peak‐to‐peak, 60 beats/min), respiratory (cos4 waveform, 30 mm peak‐to‐peak, 12 breaths/min), and a superposition of cardiac (sine waveform, 4 mm peak‐to‐peak, 70 beats/min) and respiratory (cos4 waveform, 24 mm peak‐to‐peak, 12 breaths/min). The amplitude of the motion profiles was evaluated from sagittal cine images at eight frames/s with a resolution of 2.4 mm × 2.4 mm. Gated dosimetry experiments were performed using the two module configurations for calculating dose relative to stationary. A CT‐based VT treatment plan was delivered twice under cone‐beam CT guidance and cumulative stationary doses to multi‐point PSDs were evaluated. Results: No artifacts were observed on any images acquired during phantom operation. Phantom excursions measured 49.3 ± 25.8%/66.9 ± 14.0%, 97.0 ± 2.2%/96.4 ± 1.7%, and 90.4 ± 4.8%/89.3 ± 3.5% of prescription for cardiac, respiratory, and cardio‐respiratory motion profiles for the 2‐chamber (PSD) and 12‐substructure (IC) phantom modules respectively. In the gated experiments, the cumulative dose was <2% from expected using the IC module. Real‐time dose measured for the PSDs at 10 Hz acquisition rate demonstrated the ability to detect the dosimetric consequences of cardiac, respiratory, and cardio‐respiratory motion when sampling of different locations during a single delivery, and the stability of our phantom dosimetric results over repeated cycles for the high dose and high gradient regions. For the VT delivery, high dose PSD was <1% from expected (5–6 cGy deviation of 5.9 Gy/fraction) and high gradient/low dose regions had deviations <3.6% (6.3 cGy less than expected 1.73 Gy/fraction). Conclusions: A novel multi‐modality modular heart phantom was designed, constructed, and used for gated radiotherapy experiments on a 0.35 T MR‐linac. Our phantom was capable of mimicking cardiac, cardio‐respiratory, and respiratory motion while performing dosimetric evaluations of gated procedures using IC and PSD configurations. Time‐resolved PSDs with small sensitive volumes appear promising for low‐amplitude/high‐frequency motion and multi‐point data acquisition for advanced dosimetric capabilities. Illustrating VT planning and delivery further expands our phantom to address the unmet needs of cardiac applications in radiotherapy. [ABSTRACT FROM AUTHOR]

Single-fraction stereotactic radiosurgery (SRS) or fractionated SRS (FSRS) are well established strategies for patients with limited brain metastases. A broad spectrum of modern dedicated platforms are currently available for delivering intracranial SRS/FSRS; however, SRS/FSRS delivered using traditional CT-based platforms relies on the need for diagnostic MR images to be coregistered to planning CT scans for target volume delineation. Additionally, the on-board image guidance on traditional platforms yields limited inter-fraction and intra-fraction real-time visualization of the tumor at the time of treatment delivery. MR Linacs are capable of obtaining treatment planning MR and on-table MR sequences to enable visualization of the targets and organs-at-risk and may subsequently help identify anatomical changes prior to treatment that may invoke the need for on table treatment adaptation. Recently, an MR-guided intracranial package (MRIdian A3i BrainTxTM) was released for intracranial treatment with the ability to perform high-resolution MR sequences using a dedicated brain coil and cranial immobilization system. The objective of this report is to provide, through the experience of our first patient treated, a comprehensive overview of the clinical application of our institutional program for FSRS adaptive delivery using MRIdian's A3i BrainTx system—highlights include reviewing the imaging sequence selection, workflow demonstration, and details in its delivery feasibility in clinical practice, and dosimetric outcomes. [ABSTRACT FROM AUTHOR]

Purpose: This study presents a novel and comprehensive framework for evaluating magnetic resonance guided radiotherapy (MRgRT) workflow by integrating the Failure Modes and Effects Analysis (FMEA) approach with Time‐Driven Activity‐Based Costing (TDABC). We assess the workflow for safety, quality, and economic implications, providing a holistic understanding of the MRgRT implementation. The aim is to offer valuable insights to healthcare practitioners and administrators, facilitating informed decision‐making regarding the 0.35T MRIdian MR‐Linac system's clinical workflow. Methods: For FMEA, a multidisciplinary team followed the TG‐100 methodology to assess the MRgRT workflow's potential failure modes. Following the mitigation of primary failure modes and workflow optimization, a treatment process was established for TDABC analysis. The TDABC was applied to both MRgRT and computed tomography guided RT (CTgRT) for typical five‐fraction stereotactic body RT (SBRT) treatments, assessing total workflow and costs associated between the two treatment workflows. Results: A total of 279 failure modes were identified, with 31 categorized as high‐risk, 55 as medium‐risk, and the rest as low‐risk. The top 20% risk priority numbers (RPN) were determined for each radiation oncology care team member. Total MRgRT and CTgRT costs were assessed. Implementing technological advancements, such as real‐time multi leaf collimator (MLC) tracking with volumetric modulated arc therapy (VMAT), auto‐segmentation, and increasing the Linac dose rate, led to significant cost savings for MRgRT. Conclusion: In this study, we integrated FMEA with TDABC to comprehensively evaluate the workflow and the associated costs of MRgRT compared to conventional CTgRT for five‐fraction SBRT treatments. FMEA analysis identified critical failure modes, offering insights to enhance patient safety. TDABC analysis revealed that while MRgRT provides unique advantages, it may involve higher costs. Our findings underscore the importance of exploring cost‐effective strategies and key technological advancements to ensure the widespread adoption and financial sustainability of MRgRT in clinical practice. [ABSTRACT FROM AUTHOR]

In the current era of high-precision radiation therapy, real-time magnetic resonance (MR)-guided tracking of the tumor and organs at risk (OARs) is a novel approach that enables accurate and safe delivery of high-dose radiation. Organ tracking provides a general sense of the need for daily online adaptation but lacks precise information regarding exact dosimetry. To overcome this limitation, we developed the methodology for monitoring intrafraction motion with real-time MR-guided isodose line-based tracking of an OAR in combination with anatomic tumor-based tracking and reported the first case treated with this approach. An isolated para-aortic (PA) nodal recurrence from carcinosarcoma of the endometrium was treated with an ablative dose of 50 Gy in five fractions using MR-guided radiotherapy (MRgRT). This report demonstrates the feasibility, workflow, dosimetric constraints, and treatment paradigm for real-time isodose line-based OAR tracking and gating to enable an isotoxicity delivery approach. This innovative treatment strategy effectively tracked the intrafraction motion of both the target and OAR independently and enhanced the accuracy of structure localization in time and space with a more precise dosimetric evaluation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the accuracy of different dosimeters and the treatment planning system (TPS) for assessing the skin dose due to the electron streaming effect (ESE) on a 1.5 T magnetic resonance (MR)‐linac. Method: Skin dose due to the ESE on an MR‐linac (Unity, Elekta) was investigated using a solid water phantom rotated 45° in the x‐y plane (IEC61217) and centered at the isocenter. The phantom was irradiated with 1 × 1, 3 × 3, 5 × 5, 10 × 10, and 22 × 22 cm2 fields, gantry at 90°. Out‐of‐field doses (OFDs) deposited by electron streams generated at the entry and exit surface of the angled phantom were measured on the surface of solid water slabs placed ±20.0 cm from the isocenter along the x‐direction. A high‐resolution MOSkin™ detector served as a benchmark due to its shallower depth of measurement that matches the International Commission on Radiological Protection (ICRP) recommended depth for skin dose assessment (0.07 mm). MOSkin™ doses were compared to EBT3 film, OSLDs, a diamond detector, and the TPS where the experimental setup was modeled using two separate calculation parameters settings: a 0.1 cm dose grid with 0.2% statistical uncertainty (0.1 cm, 0.2%) and a 0.2 cm dose grid with 3.0% statistical uncertainty (0.2 cm, 3.0%). Results: OSLD, film, the 0.1 cm, 0.2%, and 0.2 cm, 3.0% TPS ESE doses, underestimated skin doses measured by the MOSkin™ by as much as –75.3%, –7.0%, –24.7%, and –41.9%, respectively. Film results were most similar to MOSkin™ skin dose measurements. Conclusions: These results show that electron streams can deposit significant doses outside the primary field and that dosimeter choice and TPS calculation settings greatly influence the reported readings. Due to the steep dose gradient of the ESE, EBT3 film remains the choice for accurate skin dose assessment in this challenging environment. [ABSTRACT FROM AUTHOR]

MRI-guided radiotherapy systems enable beam gating by tracking the target on planar, two-dimensional cine images acquired during treatment. This study aims to evaluate how deep-learning (DL) models for target tracking that are trained on data from one fraction can be translated to subsequent fractions. Cine images were acquired for six patients treated on an MRI-guided radiotherapy platform (MRIdian, Viewray Inc.) with an onboard 0.35 T MRI scanner. Three DL models (U-net, attention U-net and nested U-net) for target tracking were trained using two training strategies: (1) uniform training using data obtained only from the first fraction with testing performed on data from subsequent fractions and (2) adaptive training in which training was updated each fraction by adding 20 samples from the current fraction with testing performed on the remaining images from that fraction. Tracking performance was compared between algorithms, models and training strategies by evaluating the Dice similarity coefficient (DSC) and 95% Hausdorff Distance (HD95) between automatically generated and manually specified contours. The mean DSC for all six patients in comparing manual contours and contours generated by the onboard algorithm (OBT) were 0.68 ± 0.16. Compared to OBT, the DSC values improved 17.0 − 19.3% for the three DL models with uniform training, and 24.7 − 25.7% for the models based on adaptive training. The HD95 values improved 50.6 − 54.5% for the models based on adaptive training. DL-based techniques achieved better tracking performance than the onboard, registration-based tracking approach. DL-based tracking performance improved when implementing an adaptive strategy that augments training data fraction-by-fraction. [ABSTRACT FROM AUTHOR]

Background and purpose: Patients with cardiac implantable electronic devices (CIED patients) are often ineligible for online magnetic resonance-guided radiotherapy (MRgRT), most likely due to the absence of established guidelines. Existing radiotherapy (RT) and magnetic resonance imaging (MRI) guidelines offer an opportunity to construct MRgRT protocols, promoting equitable access. Our objective was to present such a workflow, share multi-institutional experiences treating CIED patients with MRgRT on a 1.5 T magnetic resonance-linear accelerator (MR-linac), and investigate geometric accuracy and electrocardiogram (ECG) monitoring for thoracic treatment. Materials and methods: A risk analysis identified strategies for safe MRgRT for CIED patients. At three institutions, 21 pelvic and abdominal patients were treated. Patient records were analyzed for adverse events. Geometric accuracy was investigated using B0-mapping with a phantom simulating moving lung and cardiac lesions near a CIED. Volunteer measurements evaluated the effects of patient positioning and MRI sequences on ECG signal distortion. Results: MRI and RT workflows were adaptable to MRgRT. No adverse events were recorded. B0-maps showed a maximum mean difference between static and dynamic phantom configurations of 0.1 mm, increasing to 0.4 mm distortion in the presence of a CIED. ECG readings exhibited severe distortions during scanning, hampering heart rhythm detection for most MRI sequences. Conclusions: CIED patients can safely undergo treatment on a 1.5 T MR-linac following RT and MRI guidelines. For targets near CIEDs, a B0-mapping procedure was considered accurate enough to determine MRgRT eligibility. Pulse oximetry is recommended for cardiac monitoring during MRI scanning due to ECG signal distortion.

In the current era of high-precision radiation therapy, real-time magnetic resonance (MR)-guided tracking of the tumor and organs at risk (OARs) is a novel approach that enables accurate and safe delivery of high-dose radiation. Organ tracking provides a general sense of the need for daily online adaptation but lacks precise information regarding exact dosimetry. To overcome this limitation, we developed the methodology for monitoring intrafraction motion with real-time MR-guided isodose line-based tracking of an OAR in combination with anatomic tumor-based tracking and reported the first case treated with this approach. An isolated para-aortic (PA) nodal recurrence from carcinosarcoma of the endometrium was treated with an ablative dose of 50 Gy in five fractions using MR-guided radiotherapy (MRgRT). This report demonstrates the feasibility, workflow, dosimetric constraints, and treatment paradigm for real-time isodose line-based OAR tracking and gating to enable an isotoxicity delivery approach. This innovative treatment strategy effectively tracked the intrafraction motion of both the target and OAR independently and enhanced the accuracy of structure localization in time and space with a more precise dosimetric evaluation.

This study investigates the use of contrast-enhanced magnetic resonance (MR) in MR-guided adaptive radiotherapy (MRgART) for upper abdominal tumors. Contrast-enhanced T1-weighted MR (cT1w MR) using half doses of gadoterate was used to guide daily adaptive radiotherapy for tumors poorly visualized without contrast. The use of gadoterate was found to be feasible and safe in 5-fraction MRgART and could improve the contrast-to-noise ratio of MR images. And the use of cT1w MR could reduce the interobserver variation of adaptive tumor delineation compared to plain T1w MR (4.41 vs. 6.58, p

Background and purpose: Magnetic Resonance Imaging (MRI)-guided Stereotactic body radiotherapy (SBRT) treatment to prostate bed after radical prostatectomy has garnered growing interests. The aim of this study is to evaluate intra-fractional anatomic and dose/volume metric variations for patients receiving this treatment. Materials and methods: Nineteen patients who received 30–34 Gy in 5 fractions on a 0.35T MR-Linac were included. Pre- and post-treatment MRIs were acquired for each fraction (total of 75 fractions). The Clinical Target Volume (CTV), bladder, rectum, and rectal wall were contoured on all images. Volumetric changes, Hausdorff distance, Mean Distance to Agreement (MDA), and Dice similarity coefficient (DSC) for each structure were calculated. Median value and Interquartile range (IQR) were recorded. Changes in target coverage and Organ at Risk (OAR) constraints were compared and evaluated using Wilcoxon rank sum tests at a significant level of 0.05. Results: Bladder had the largest volumetric changes, with a median volume increase of 48.9 % (IQR 28.9–76.8 %) and a median MDA of 5.1 mm (IQR 3.4–7.1 mm). Intra-fractional CTV volume remained stable with a median volume change of 1.2 % (0.0–4.8 %). DSC was 0.97 (IQR 0.94–0.99). For the dose/volume metrics, there were no statistically significant changes observed except for an increase in bladder hotspot and a decrease of bladder V32.5 Gy and mean dose. The CTV V95% changed from 99.9 % (IQR 98.8–100 %) to 99.6 % (IQR 93.9–100 %). Conclusion: Despite intra-fractional variations of OARs, CTV coverage remained stable during MRI-guided SBRT treatments for the prostate bed.

Background and Purpose: Online adaptive MR-guided radiotherapy (MRgRT) is a relatively new form of radiotherapy treatment, delivered using a MR-Linac. It is unknown what patients expect from this treatment and whether these expectations are met. This study evaluates whether patients’ pre-treatment expectations of MRgRT are met and reports patients’ on-table experience on a 1.5 T MR-Linac. Materials and methods: All patients treated on the MR-Linac from November 2020 until April 2021, were eligible for inclusion. Patient expectation and experience were captured through questionnaires before, during, and three months after treatment. The on-table experience questionnaire included patient’ physical and psychological coping. Patient-expected side effects, participation in daily and social activity, disease outcome and, disease related symptoms were compared to post-treatment experience. Results: We included 113 patients who were primarily male (n = 100, 89 %), with a median age of 69 years (range 52–90). For on-table experience, ninety percent of patients (strongly) agreed to feeling calm during their treatment. Six and eight percent of patients found the treatment position or bed uncomfortable respectively. Twenty-eight percent of patients felt tingling sensations during treatment. After treatment, 79 % of patients’ expectations were met. Most patients experienced an (better than) expected level of side effects (75 %), participation in daily- (83 %) and social activity (86 %) and symptoms (78 %). However, 33 % expected more treatment efficacy than experienced. Conclusion: Treatment on the 1.5 T MR-Linac is well tolerated and meets patient expectations. Despite the fact that some patients expected greater treatment efficacy and the frequent occurrence of tingling sensations during treatment, most patient experiences were comparable or better than previously expected.

Introduction: Stereotactic MR-guided on-table adaptive radiotherapy (SMART) allows the precise delivery of high-dose radiation to tumors in great proximity to radiation-sensitive organs. The aim of this study is to evaluate the toxicity and clinical outcome in locally advanced or recurrent pancreatic tumors, with or without prior irradiation, treated with SMART. Methods: Patients were treated for pancreatic cancer (PC) using SMART technology to a prescribed dose of 50 Gy (BED10, 100 Gy) in five fractions, with daily on-table adaptation of treatment plan. Endpoints were acute and late toxicities, local control, local disease-free period, and overall survival. Results: A total of 54 PC patients were treated between August 2019 and September 2022, with a median follow-up of 8.9 months from SMART. The median age was 70.4 (45.2--86.9) years. A total of 40 patients had upfront inoperable PC (55% were locally advanced and 45% metastatic), and 14 had local recurrence following prior pancreatectomy (six patients also had prior adjuvant RT). Of the patients, 87% received at least one chemotherapy regimen (Oxaliplatin based, 72.2%), and 25.9% received ≥2 regimens. Except from lower CA 19-9 serum level at the time of diagnosis and 6 weeks prior to SMART in previously operated patients, there were no significant differences in baseline parameters between prior pancreatectomy and the inoperable group. On-table adaptive replanning was performed for 100% of the fractions. No patient reported grade ≥2 acute GI toxicity. All previously irradiated patients reported only low-grade toxicities during RT. A total of 48 patients (88.9%) were available for evaluation. Complete local control was achieved in 21.7% (10 patients) for a median of 9 months (2.8--28.8); three had later local progression. Eight patients had regional or marginal recurrence. Six- and 12-month OS were 75.0% and 52.1%, respectively. Apart from mild diarrhea 1--3 months after SMART and general fatigue, there were no significant differences in toxicity and outcomes between post-pancreatectomy and inoperable groups. Conclusion: SMART allows safe delivery of an ablative dose of radiotherapy, with minimal treatment-related toxicity, even in previously resected or irradiated patients. In this real-world cohort, local control with complete response was achieved by 20% of the patients. Further studies are needed to evaluate longterm outcome and late toxicity. [ABSTRACT FROM AUTHOR]

Introduction: Patients treatment compliance increases during free-breathing (FB) treatment, taking generally less time and fatigue with respect to deep inspiration breath-hold (DIBH). This study quantifies the gross target volume (GTV) motion on cine-MRI of apical lung lesions undergoing a SBRT in a MRLinac and supports the patient specific treatment gating pre-selection. Material and methods: A total of 12 patients were retrospectively enrolled in this study. During simulation and treatment fractions, sagittal 0.35 T cine-MRI allows real-time GTV motion tracking. Cine-MRI has been exported, and an in-house developed MATLAB script performed image segmentation for measuring GTV centroid position on cine-MRI frames. Motion measurements were performed during the deep inspiration phase of DIBH patient and during all the session for FB patient. Treatment plans of FB patients were reoptimized using the same cost function, choosing the 3 mm GTV-PTV margin used for DIBH patients instead of the original 5 mm margin, comparing GTV and OARs DVH for the different TP. Results: GTV centroidmotion is <2.2mmin the antero-posterior and cranio-caudal direction in DIBH. For FB patients, GTV motion is lower than 1.7 mm, and motion during the treatment was always in agreement with the one measured during the simulation. No differences have been observed in GTV coverage between the TP with 3-mm and 5-mm margins. Using a 3-mm margin, the mean reduction in the chest wall and trachea-bronchus Dmax was 2.5 Gy and 3.0 Gy, respectively, and a reduction of 1.0 Gy, 0.6 Gy, and 2.3% in Dmax, Dmean, and V5Gy, respectively, of the homolateral lung and 1.7 Gy in the contralateral lung Dmax. Discussions: Cine-MRI allows to select FB lung patients when GTVmotion is <2mm. The use of narrower PTV margins reduces OARs dose and maintains target coverage. [ABSTRACT FROM AUTHOR]

Introduction: Contouring of gas pockets is a time consuming step in the workflow of adaptive radiotherapy. We would like to better understand which gas pockets electronic densitiy should be used and the dosimetric impact on adaptive MRgRT treatment. Materials and methods: 21 CT scans of patients undergoing SBRT were retrospectively evaluated. Anatomical structures were contoured: Gross Tumour Volume (GTV), stomach (ST), small bowel (SB), large bowel (LB), gas pockets (GAS) and gas in each organ respectively STG, SBG, LBG. Average HU in GAS was converted in RED, the obtained value has been named as Gastrointestinal Gas RED (GIGED). Differences of average HU in GAS, STG, SBG and LBG were computed. Three treatment plans were calculated editing the GAS volume RED that was overwritten with: air RED (0.0012), water RED (1.000), GIGED, generating respectively APLAN, WPLAN and the GPLAN. 2-D dose distributions were analyzed by gamma analysis. Parameter called active gas volume (AGV) was calculated as the intersection of GAS with the isodose of 5% of prescription dose. Results: Average HU value contained in GAS results to be equal to -620. No significative difference was noted between the average HU of gas in different organ at risk. Value of Gamma Passing Rate (GPR) anticorrelates with the AGV for each plan comparison and the threshold value for GPR to fall below 90% is 41, 60 and 139 cc for WPLANvsAPLAN, GPLANvsAPLAN and WPLANvsGPLAN respectively. Discussions: GIGED is the right RED for Gastrointestinal Gas. Novel AGV is a useful parameter to evaluate the effect of gas pocket on dose distribution. [ABSTRACT FROM AUTHOR]

Simple Summary: Magnetic resonance imaging (MRI) has several advantages over computerized tomography (CT) in the treatment planning of central nervous system (CNS) malignancies. The adoption of hybrid MRI and linear accelerators (MRLs) has allowed for more effective tumor control and reduced unnecessary neurotoxicity through precise daily adaptations. In this review, we provide a summary of the evidence for MRLs in the management of various CNS tumors. Additionally, we discuss the potential of multiparametric MRI and genomically guided radiotherapy to enhance patient outcomes. Magnetic resonance imaging (MRI) provides excellent visualization of central nervous system (CNS) tumors due to its superior soft tissue contrast. Magnetic resonance-guided radiotherapy (MRgRT) has historically been limited to use in the initial treatment planning stage due to cost and feasibility. MRI-guided linear accelerators (MRLs) allow clinicians to visualize tumors and organs at risk (OARs) directly before and during treatment, a process known as online MRgRT. This novel system permits adaptive treatment planning based on anatomical changes to ensure accurate dose delivery to the tumor while minimizing unnecessary toxicity to healthy tissue. These advancements are critical to treatment adaptation in the brain and spinal cord, where both preliminary MRI and daily CT guidance have typically had limited benefit. In this narrative review, we investigate the application of online MRgRT in the treatment of various CNS malignancies and any relevant ongoing clinical trials. Imaging of glioblastoma patients has shown significant changes in the gross tumor volume over a standard course of chemoradiotherapy. The use of adaptive online MRgRT in these patients demonstrated reduced target volumes with cavity shrinkage and a resulting reduction in radiation dose to uninvolved tissue. Dosimetric feasibility studies have shown MRL-guided stereotactic radiotherapy (SRT) for intracranial and spine tumors to have potential dosimetric advantages and reduced morbidity compared with conventional linear accelerators. Similarly, dosimetric feasibility studies have shown promise in hippocampal avoidance whole brain radiotherapy (HA-WBRT). Next, we explore the potential of MRL-based multiparametric MRI (mpMRI) and genomically informed radiotherapy to treat CNS disease with cutting-edge precision. Lastly, we explore the challenges of treating CNS malignancies and special limitations MRL systems face. [ABSTRACT FROM AUTHOR]

Background and Purpose: In the emerging paradigm of stereotactic radiosurgery being proposed for MR‐guided radiotherapy (MRgRT), assessment of mechanical geometric accuracy is critical for the implementation of stereotactic delivery. We benchmarked the mechanical accuracy of an MR Linac system that lacks an onboard detector/array. Our mechanical tests utilize a half beam block (HBB) geometry that takes advantage of the sensitivity of a partially occluded detector. Materials and Methods: Mechanical tests benchmarked the couch, MLC, and gantry geometric accuracy for an MR‐Linac system. An HBB technique was used to irradiate an ionization chamber profiler (ICP) array with partial occlusion of individual detectors for characterization of MLC skew, beam divergence displacement, and RT isocenter localization. The sensitivity of the partially occluded detector's ICP‐X (detector width) and ICP‐Y (detector length) was characterized by displacing the detector relative to radiation isocenter by 0.2 mm increments, introduced through couch motion. The accuracy of the HBB ICP technique was verified with a starshot using radiochromic film, and the reproducibility was verified on a conventional C‐arm Linac and compared to Winston‐Lutz. Results: The sensitivity of the HBB technique as quantified through the dose difference normalized to open field as a function of displacement from RT isocenter was 6.4%/mm and 13.0%/mm for the ICP‐X and ICP‐Y orientation, respectively, due to the oblong detector orientation. Couch positional accuracy and sag was within ±0.1 mm. Maximum MLC positional displacement was 0.7 mm with mean MLC skew at 0.07°. The maximum beam divergence displacement was 0.03 mm. The gantry angle was within 0.1°. Independent verification of the RT isocenter localization procedure produced repeatable results. Conclusion: This work serves for characterizing the mechanical and geometric radiation accuracy for the foundation of an MR‐guided stereotactic radiosurgery program, as demonstrated with high sensitivity and independent validation. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance (MR)‐guided radiation therapy provides capabilities to utilize high‐resolution and real‐time MR imaging before and during treatment, which is critical for adaptive radiotherapy. This emerging modality has been promptly adopted in the clinic settings in advance of adaptations to reference dosimetry formalism that are needed to account for the presence of strong magnetic fields. In particular, the influence of magnetic field on the uncertainty of parameters in the reference dosimetry equation needs to be determined in order to fully characterize the uncertainty budget for reference dosimetry in MR‐guided radiation therapy systems. Purpose: To identify and quantify key sources of uncertainty in the reference dosimetry of external high energy radiotherapy beams in the presence of a strong magnetic field. Methods: In the absence of a formalized Task Group report for reference dosimetry in MR‐integrated linacs, the currently suggested formalism follows the TG‐51 protocol with the addition of a quality conversion factor kBQ accounting for the effects of the magnetic field on ionization chamber response. In this work, we quantify various sources of uncertainty that impact each of the parameters in the formalism, and evaluate their overall contribution to the final dose. Measurements are done in a 1.5 T MR‐Linac (Unity, Elekta AB, Stockholm, Sweden) which integrates a 1.5 T Philips MR scanner and a 7 MVFFF linac. The responses of several reference‐class small volume ionization chambers (Exradin:A1SL, IBA:CC13, PTW:Semiflex‐3D) and Farmer type ionization chambers (Exradin:A19, IBA:FC65‐G) were evaluated throughout this process. Long‐term reproducibility and stability of beam quality, TPR1020${\mathrm{TPR}}_{10}^{20}$, was also measured with an in‐house built phantom. Results: Relative to the conventional external high energy linacs, the uncertainty on overall reference dose in MR‐linac is more significantly affected by the chamber setup: A translational displacement along y‐axis of ± 3 mm results in dose variation of < |0.20| ± 0.02% (k = 1), while rotation of ± 5° in horizontal and vertical parallel planes relative to relative to the direction of magnetic field, did not exceed variation of < |0.44| ± 0.02% for all 5 ionization chambers. We measured a larger dose variation for xy‐plane (horizontal) rotations (< |0.44| ± 0.02% (k = 1)) than for yz‐plane (vertical) rotations (< ||0.28| ± 0.02% (k = 1)), which we associate with the gradient of kB,Q as a function of chamber orientation with respect to direction of the B0‐field. Uncertainty in Pion (for two depths), Ppol (with various sub‐studies including effects of cable length, cable looping in the MRgRT bore, connector type in magnetic environment), and Prp were determined. Combined conversion factor kQ× kB,Q was provided for two reference depths at four cardinal angle orientations. Over a two‐year period, beam quality was quite stable with TPR1020${\mathrm{TPR}}_{10}^{20}$ being 0.669 ± 0.01%. The actual magnitude of TPR1020${\mathrm{TPR}}_{10}^{20}$ was measured using identical equipment and compared between two different Elekta Unity MR‐Linacs with results agreeing to within 0.21%. Conclusion: In this work, the uncertainty of a number of parameters influencing reference dosimetry was quantified. The results of this work can be used to identify best practice guidelines for reference dosimetry in the presence of magnetic fields, and to evaluate an uncertainty budget for future reference dosimetry protocols for MR‐linac. [ABSTRACT FROM AUTHOR]

The past decade has seen the increasing integration of magnetic resonance (MR) imaging into radiation therapy (RT). This growth can be contributed to multiple factors, including hardware and software advances that have allowed the acquisition of high-resolution volumetric data of RT patients in their treatment position (also known as MR simulation) and the development of methods to image and quantify tissue function and response to therapy. More recently, the advent of MR-guided radiation therapy (MRgRT) - achieved through the integration of MR imaging systems and linear accelerators - has further accelerated this trend. As MR imaging in RT techniques and technologies, such as MRgRT, gain regulatory approval worldwide, these systems will begin to propagate beyond tertiary care academic medical centers and into more community-based health systems and hospitals, creating new opportunities to provide advanced treatment options to a broader patient population. Accompanying these opportunities are unique challenges related to their adaptation, adoption, and use including modification of hardware and software to meet the unique and distinct demands of MR imaging in RT, the need for standardization of imaging techniques and protocols, education of the broader RT community (particularly in regards to MR safety) as well as the need to continue and support research, and development in this space. In response to this, an ad hoc committee of the American Association of Physicists in Medicine (AAPM) was formed to identify the unmet needs, roadblocks, and opportunities within this space. The purpose of this document is to report on the major findings and recommendations identified. Importantly, the provided recommendations represent the consensus opinions of the committee's membership, which were submitted in the committee's report to the AAPM Board of Directors. In addition, AAPM ad hoc committee reports differ from AAPM task group reports in that ad hoc committee reports are neither reviewed nor ultimately approved by the committee's parent groups, including at the council and executive committee level. Thus, the recommendations given in this summary should not be construed as being endorsed by or official recommendations from the AAPM.

PurposeTo estimate the overall spatial distortion on clinical patient images for a 0.35 T MR-guided radiotherapy system.MethodsTen patients with head-and-neck cancer underwent CT and MR simulations with identical immobilization. The MR images underwent the standard systematic distortion correction post-processing. The images were rigidly registered and landmark-based analysis was performed by an anatomical expert. Distortion was quantified using Euclidean distance between each landmark pair and tagged by tissue interface: bone-tissue, soft tissue, or air-tissue. For baseline comparisons, an anthropomorphic phantom was imaged and analyzed.ResultsThe average spatial discrepancy between CT and MR landmarks was 1.15 ± 1.14 mm for the phantom and 1.46 ± 1.78 mm for patients. The error histogram peaked at 0-1 mm. 66% of the discrepancies were

PURPOSE: To evaluate geometric variations of patients receiving stereotactic body radiotherapy (SBRT) after radical prostatectomy and the dosimetric benefits of stereotactic MRI guided adaptive radiotherapy (SMART) to compensate for these variations. MATERIALS/METHODS: The CTV and OAR were contoured on 55 MRI setup scans of 11 patients treated with an MR-LINAC and enrolled in a phase II trial of post-prostatectomy SBRT. All patients followed institutional bladder and rectum preparation protocols and received five fractions of 6-6.8 Gy to the prostate bed. Interfractional changes in volume were calculated and shape deformation was quantified by the Dice similar coefficient (DSC). Changes in CTV-V95%, bladder and rectum maximum dose, V32.5Gy and V27.5Gy were predicted by recalculating the initial plan on daily MRI. SMART was retrospectively simulated if the predicted dose exceeded pre-set criteria. RESULTS: The CTV volume and shape remained stable with a median volumetric change of 3.0% (IQR -3.0% to 11.5%) and DSC of 0.83 (IQR 0.79 to 0.88). Relatively large volumetric changes in bladder (median -24.5%, IQR -34.6% to 14.5%) and rectum (median 5.4%, IQR - 9.7% to 20.7%) were observed while shape changes were moderate (median DSC of 0.79 and 0.73, respectively). The median CTV-V95% was 98.4% (IQR 94.9% to 99.6%) for the predicted doses. However, SMART would have been deemed beneficial for 78.2% of the 55 fractions based on target undercoverage (16.4%), exceeding OAR constraints (50.9%), or both (10.9%). Simulated SMART improved the dosimetry and met dosimetric criteria in all fractions. Moderate correlations were observed between the CTV-V95% and target DSC (R2 = 0.73) and bladder mean dose versus volumetric changes (R2 = 0.61). CONCLUSIONS: Interfractional dosimetric variations resulting from anatomic deformation are commonly encountered with post-prostatectomy RT and can be mitigated with SMART.

Abstract Aims Reirradiation of prostate cancer (PC) local recurrences represents an emerging challenge for current radiotherapy. In this context, stereotactic body radiation therapy (SBRT) allows the delivery of high doses, with curative intent. Magnetic Resonance guided Radiation Therapy (MRgRT) has shown promising results in terms of safety, feasibility and efficacy of delivering SBRT thanks to the enhanced soft tissue contrast and the online adaptive workflow. This multicentric retrospective analysis evaluates the feasibility and efficacy of PC reirradiation, using a 0.35 T hybrid MR delivery unit. Methods Patients affected by local recurrences of PC and treated in five institutions between 2019 and 2022 were retrospectively collected. All patients had undergone previous Radiation Therapy (RT) in definitive or adjuvant setting. Re-treatment MRgSBRT was delivered with a total dose ranging from 25 to 40 Gy in 5 fractions. Toxicity according to CTCAE v 5.0 and treatment response were assessed at the end of the treatment and at follow-up. Results Eighteen patients were included in this analysis. All patients had previously undergone external beam radiation therapy (EBRT) up to a total dose of 59.36 to 80 Gy. Median cumulative biologically effective dose (BED) of SBRT re-treatment was 213,3 Gy (103,1-560), considering an α/β of 1.5. Complete response was achieved in 4 patients (22.2%). No grade ≥ 2 acute genitourinary (GU) toxicity events were recorded, while gastrointestinal (GI) acute toxicity events occurred in 4 patients (22.2%). Conclusion The low rates of acute toxicity of this experience encourages considering MRgSBRT a feasibile therapeutic approach for the treatment of clinically relapsed PC. Accurate gating of target volumes, the online adaptive planning workflow and the high definition of MRI treatment images allow delivering high doses to the PTV while efficiently sparing organs at risk (OARs).

Background and purpose: Ultra-hypofractionated online adaptive magnetic resonance-guided radiotherapy (MRgRT) is promising for prostate cancer. However, the impact of online adaptation on target coverage and organ-at-risk (OAR) sparing at the level of accumulated dose has not yet been reported. Using deformable image registration (DIR)-based accumulation, we compared the delivered adapted dose with the simulated non-adapted dose. Materials and methods: Twenty-three prostate cancer patients treated at two clinics with 0.35 T magnetic resonance-guided linear accelerator (MR-linac) following the same treatment protocol (5 × 7.5 Gy with urethral sparing and daily adaptation) were included. The fraction MR images were deformably registered to the planning MR image. Both non-adapted and adapted fraction doses were accumulated with the corresponding vector fields. Two DIR approaches were implemented. PTV* (planning target volume minus urethra+2mm) D95%, CTV* (clinical target volume minus urethra) D98%, and OARs (urethra+2mm, bladder, and rectum) D0.2cc, were evaluated. Statistical significance was inferred from a two-tailed Wilcoxon signed-rank test (p

IntroductionStereotactic MR-guided on-table adaptive radiotherapy (SMART) allows the precise delivery of high-dose radiation to tumors in great proximity to radiation-sensitive organs. The aim of this study is to evaluate the toxicity and clinical outcome in locally advanced or recurrent pancreatic tumors, with or without prior irradiation, treated with SMART.MethodsPatients were treated for pancreatic cancer (PC) using SMART technology to a prescribed dose of 50 Gy (BED10, 100 Gy) in five fractions, with daily on-table adaptation of treatment plan. Endpoints were acute and late toxicities, local control, local disease-free period, and overall survival.ResultsA total of 54 PC patients were treated between August 2019 and September 2022, with a median follow-up of 8.9 months from SMART. The median age was 70.4 (45.2–86.9) years. A total of 40 patients had upfront inoperable PC (55% were locally advanced and 45% metastatic), and 14 had local recurrence following prior pancreatectomy (six patients also had prior adjuvant RT). Of the patients, 87% received at least one chemotherapy regimen (Oxaliplatin based, 72.2%), and 25.9% received ≥2 regimens. Except from lower CA 19-9 serum level at the time of diagnosis and 6 weeks prior to SMART in previously operated patients, there were no significant differences in baseline parameters between prior pancreatectomy and the inoperable group. On-table adaptive replanning was performed for 100% of the fractions. No patient reported grade ≥2 acute GI toxicity. All previously irradiated patients reported only low-grade toxicities during RT. A total of 48 patients (88.9%) were available for evaluation. Complete local control was achieved in 21.7% (10 patients) for a median of 9 months (2.8–28.8); three had later local progression. Eight patients had regional or marginal recurrence. Six- and 12-month OS were 75.0% and 52.1%, respectively. Apart from mild diarrhea 1–3 months after SMART and general fatigue, there were no significant differences in toxicity and outcomes between post-pancreatectomy and inoperable groups.ConclusionSMART allows safe delivery of an ablative dose of radiotherapy, with minimal treatment-related toxicity, even in previously resected or irradiated patients. In this real-world cohort, local control with complete response was achieved by 20% of the patients. Further studies are needed to evaluate long-term outcome and late toxicity.

IntroductionPatients treatment compliance increases during free-breathing (FB) treatment, taking generally less time and fatigue with respect to deep inspiration breath-hold (DIBH). This study quantifies the gross target volume (GTV) motion on cine-MRI of apical lung lesions undergoing a SBRT in a MR-Linac and supports the patient specific treatment gating pre-selection.Material and methodsA total of 12 patients were retrospectively enrolled in this study. During simulation and treatment fractions, sagittal 0.35 T cine-MRI allows real-time GTV motion tracking. Cine-MRI has been exported, and an in-house developed MATLAB script performed image segmentation for measuring GTV centroid position on cine-MRI frames. Motion measurements were performed during the deep inspiration phase of DIBH patient and during all the session for FB patient. Treatment plans of FB patients were reoptimized using the same cost function, choosing the 3 mm GTV-PTV margin used for DIBH patients instead of the original 5 mm margin, comparing GTV and OARs DVH for the different TP.ResultsGTV centroid motion is

IntroductionContouring of gas pockets is a time consuming step in the workflow of adaptive radiotherapy. We would like to better understand which gas pockets electronic densitiy should be used and the dosimetric impact on adaptive MRgRT treatment.Materials and methods21 CT scans of patients undergoing SBRT were retrospectively evaluated. Anatomical structures were contoured: Gross Tumour Volume (GTV), stomach (ST), small bowel (SB), large bowel (LB), gas pockets (GAS) and gas in each organ respectively STG, SBG, LBG. Average HU in GAS was converted in RED, the obtained value has been named as Gastrointestinal Gas RED (GIGED). Differences of average HU in GAS, STG, SBG and LBG were computed. Three treatment plans were calculated editing the GAS volume RED that was overwritten with: air RED (0.0012), water RED (1.000), GIGED, generating respectively APLAN, WPLAN and the GPLAN. 2-D dose distributions were analyzed by gamma analysis. Parameter called active gas volume (AGV) was calculated as the intersection of GAS with the isodose of 5% of prescription dose.ResultsAverage HU value contained in GAS results to be equal to -620. No significative difference was noted between the average HU of gas in different organ at risk. Value of Gamma Passing Rate (GPR) anticorrelates with the AGV for each plan comparison and the threshold value for GPR to fall below 90% is 41, 60 and 139 cc for WPLANvsAPLAN, GPLANvsAPLAN and WPLANvsGPLAN respectively.DiscussionsGIGED is the right RED for Gastrointestinal Gas. Novel AGV is a useful parameter to evaluate the effect of gas pocket on dose distribution.

Background and purpose: The optimal stereotactic ablative radiotherapy (SABR) doses for adrenal tumors are unknown. Some trials have specified that organ at risk (OAR) dose constraints should take priority over target coverage. We performed a retrospective review of the outcomes of MR-guided adrenal SABR (MRgRT) delivered with OAR sparing. Materials and methods: Patients who underwent adrenal MRgRT between 2016 and 2023 were identified from our Ethics-approved institutional database. Dose ranged between 8 and 24 Gy per fraction, delivered in 1–5 fractions. A 3 mm margin was added to the breath-hold gross tumor volume (GTV) to derive a PTV. Plan were delivered to an ‘optimized’ PTV that was generated by excluding any overlap with OARs. Results: Adrenal SABR was performed in 107 patients (114 metastases). The commonest scheme used 5 fractions of 10 Gy (53.5 %); 82 % of plans delivered a BED10 ≧ 80 Gy. Systemic therapy was administered within 3 months preceding or following SABR in 53.5 % of patients. Grade 3 acute toxicity (CTCAE v5.0) occurred in 0.9 % of patients, and 4.4 % reported late toxicity, consisting of adrenal insufficiency and a vertebral collapse. Median follow-up was 13.8 months (range, 0.0–73.4 months). Local progression occurred in 7.4 % of evaluable patients. PTV underdosage was frequent, with a coverage compromise index (D99/prescription dose) of

Few studies have examined the cardiac volume and radiation dose differences among cardiac phases during radiation therapy (RT). Such information is crucial to dose reconstruction and understanding of RT related cardiac toxicity. In a cohort of nine patients, we studied the changes in the volume and doses of several cardiac substructures between the end-diastolic and end-systolic phases based on the clinical magnetic resonance-guided RT (MRgRT) treatment plans. Significant differences in the volume and dose between the two phases were observed. Onboard cardiac cine MRI holds promise for patient-specific cardiac sparing treatment designs.

Introduction: Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is a promising treatment modality for pancreatic cancer and is being employed by an increasing number of centers worldwide. However, clinical outcomes have only been reported on a small scale, often from single institutes and in the context of clinical trials, in which strict patient selection might limit generalizability of outcomes. This study presents clinical outcomes of a large, international cohort of patients with (peri)pancreatic tumors treated with online adaptive MRgRT. Methods: We evaluated clinical outcomes and treatment details of patients with (peri)pancreatic tumors treated on a 1.5 Tesla (T) MR-linac in two large-volume treatment centers participating in the prospective MOMENTUM cohort (NCT04075305). Treatments were evaluated through schematics, dosage, delivery strategies, and success rates. Acute toxicity was assessed until 3 months after MRgRT started, and late toxicity from 3-12 months of follow-up (FU). The EORTC QLQ-C30 questionnaire was used to evaluate the quality of life (QoL) at baseline and 3 months of FU. Furthermore, we used the Kaplan-Meier analysis to calculate the cumulative overall survival. Results: A total of 80 patients were assessed with a median FU of 8 months (range 1-39 months). There were 34 patients who had an unresectable primary tumor or were medically inoperable, 29 who had an isolated local recurrence, and 17 who had an oligometastasis. A total of 357 of the 358 fractions from all hypofractionated schemes were delivered as planned. Grade 3-4 acute toxicity occurred in 3 of 59 patients (5%) with hypofractionated MRgRT and grade 3-4 late toxicity in 5 of 41 patients (12%). Six patients died within 3 months after MRgRT; in one of these patients, RT attribution could not be ruled out as cause of death. The QLQ-C30 global health status remained stable from baseline to 3 months FU (70.5 at baseline, median change of +2.7 [P = 0.5]). The 1-year cumulative overall survival for the entire cohort was 67%, and that for the primary tumor group was 66%. Conclusion: Online adaptive MRgRT for (peri)pancreatic tumors on a 1.5 T MRLinac could be delivered as planned, with low numbers of missed fractions. In addition, treatments were associated with limited grade 3-4 toxicity and a stable QoL at 3 months of FU. [ABSTRACT FROM AUTHOR]

Abstract Recent years have seen both a fresh knowledge of cancer and impressive advancements in its treatment. However, the clinical treatment paradigm of cancer is still difficult to implement in the twenty-first century due to the rise in its prevalence. Radiotherapy (RT) is a crucial component of cancer treatment that is helpful for almost all cancer types. The accuracy of RT dosage delivery is increasing as a result of the quick development of computer and imaging technology. The use of image-guided radiation (IGRT) has improved cancer outcomes and decreased toxicity. Online adaptive radiotherapy will be made possible by magnetic resonance imaging-guided radiotherapy (MRgRT) using a magnetic resonance linear accelerator (MR-Linac), which will enhance the visibility of malignancies. This review's objectives are to examine the benefits of MR-Linac as a treatment approach from the perspective of various cancer patients' prognoses and to suggest prospective development areas for additional study.

Abstract Background Significant comorbidities, advanced age, and a poor performance status prevent surgery and systemic treatment for many patients with localized (non-metastatic) pancreatic ductal adenocarcinoma (PDAC). These patients are currently treated with ‘best supportive care’. Therefore, it is desirable to find a treatment option which could improve both disease control and quality of life in these patients. A brief course of high-dose high-precision radiotherapy i.e. stereotactic ablative body radiotherapy (SABR) may be feasible. Methods A nationwide multicenter trial performed within a previously established large prospective cohort (the Dutch Pancreatic cancer project; PACAP) according to the ‘Trial within cohorts’ (TwiCs) design. Patients enrolled in the PACAP cohort routinely provide informed consent to answer quality of life questionnaires and to be randomized according to the TwiCs design when eligible for a study. Patients with localized PDAC who are unfit for chemotherapy and surgery or those who refrain from these treatments are eligible. Patients will be randomized between SABR (5 fractions of 8 Gy) with ‘best supportive care’ and ‘best supportive care’ only. The primary endpoint is overall survival from randomization. Secondary endpoints include preservation of quality of life (EORTC-QLQ-C30 and -PAN26), NRS pain score response and WHO performance scores at baseline, and, 3, 6 and 12 months. Acute and late toxicity will be scored using CTCAE criteria version 5.0: assessed at baseline, day of last fraction, at 3 and 6 weeks, and 3, 6 and 12 months following SABR. Discussion The PANCOSAR trial studies the added value of SBRT as compared to ‘best supportive care’ in patients with localized PDAC who are medically unfit to receive chemotherapy and surgery, or refrain from these treatments. This study will assess whether SABR, in comparison to best supportive care, can relieve or delay tumor-related symptoms, enhance quality of life, and extend survival in these patients. Trial registration Clinical trials, NCT05265663 , Registered March 3 2022, Retrospectively registered.

Background and purpose: The 1.5 Tesla (T) Magnetic Resonance Linear Accelerator (MRL) provides an innovative modality for improved cardiac imaging when planning radiation treatment. No MRL based cardiac atlases currently exist, thus, we sought to comprehensively characterize cardiac substructures, including the conduction system, from cardiac images acquired using a 1.5 T MRL and provide contouring guidelines. Materials and methods: Five volunteers were enrolled in a prospective protocol (NCT03500081) and were imaged on the 1.5 T MRL with Half Fourier Single-Shot Turbo Spin-Echo (HASTE) and 3D Balanced Steady-State Free Precession (bSSFP) sequences in axial, short axis, and vertical long axis. Cardiac anatomy was contoured by (AS) and confirmed by a board certified cardiologist (JR) with expertise in cardiac MR imaging. Results: A total of five volunteers had images acquired with the HASTE sequence, with 21 contours created on each image. One of these volunteers had additional images obtained with 3D bSSFP sequences in the axial plane and additional images obtained with HASTE sequences in the key cardiac planes. Contouring guidelines were created and outlined. 15–16 contours were made for the short axis and vertical long axis. The cardiac conduction system was demonstrated with eleven representative contours. There was reasonable variation of contour volume across volunteers, with structures more clearly delineated on the 3D bSSFP sequence. Conclusions: We present a comprehensive cardiac atlas using novel images acquired prospectively on a 1.5 T MRL. This cardiac atlas provides a novel resource for radiation oncologists in delineating cardiac structures for treatment with radiotherapy, with special focus on the cardiac conduction system.

Background and purpose: Automation is desirable for organ segmentation in radiotherapy. This study compared deep learning methods for auto-segmentation of organs-at-risk (OARs) and clinical target volume (CTV) in prostate cancer patients undergoing fractionated magnetic resonance (MR)-guided adaptive radiation therapy. Models predicting dense displacement fields (DDFMs) between planning and fraction images were compared to patient-specific (PSM) and baseline (BM) segmentation models. Materials and methods: A dataset of 92 patients with planning and fraction MR images (MRIs) from two institutions were used. DDFMs were trained to predict dense displacement fields (DDFs) between the planning and fraction images, which were subsequently used to propagate the planning contours of the bladder, rectum, and CTV to the daily MRI. The training was performed either with true planning-fraction image pairs or with planning images and their counterparts deformed by known DDFs. The BMs were trained on 53 planning images, while to generate PSMs, the BMs were fine-tuned using the planning image of a given single patient. The evaluation included Dice similarity coefficient (DSC), the average (HDavg) and the 95th percentile (HD95) Hausdorff distance (HD). Results: The DDFMs with DSCs for bladder/rectum of 0.76/0.76 performed worse than PSMs (0.91/0.90) and BMs (0.89/0.88). The same trend was observed for HDs. For CTV, DDFM and PSM performed similarly yielding DSCs of 0.87 and 0.84, respectively. Conclusions: DDFMs were found suitable for CTV delineation after rigid alignment. However, for OARs they were outperformed by PSMs, as they predicted only limited deformations even in the presence of substantial anatomical changes.

IntroductionOnline adaptive magnetic resonance-guided radiotherapy (MRgRT) is a promising treatment modality for pancreatic cancer and is being employed by an increasing number of centers worldwide. However, clinical outcomes have only been reported on a small scale, often from single institutes and in the context of clinical trials, in which strict patient selection might limit generalizability of outcomes. This study presents clinical outcomes of a large, international cohort of patients with (peri)pancreatic tumors treated with online adaptive MRgRT.MethodsWe evaluated clinical outcomes and treatment details of patients with (peri)pancreatic tumors treated on a 1.5 Tesla (T) MR-linac in two large-volume treatment centers participating in the prospective MOMENTUM cohort (NCT04075305). Treatments were evaluated through schematics, dosage, delivery strategies, and success rates. Acute toxicity was assessed until 3 months after MRgRT started, and late toxicity from 3–12 months of follow-up (FU). The EORTC QLQ-C30 questionnaire was used to evaluate the quality of life (QoL) at baseline and 3 months of FU. Furthermore, we used the Kaplan–Meier analysis to calculate the cumulative overall survival.ResultsA total of 80 patients were assessed with a median FU of 8 months (range 1–39 months). There were 34 patients who had an unresectable primary tumor or were medically inoperable, 29 who had an isolated local recurrence, and 17 who had an oligometastasis. A total of 357 of the 358 fractions from all hypofractionated schemes were delivered as planned. Grade 3–4 acute toxicity occurred in 3 of 59 patients (5%) with hypofractionated MRgRT and grade 3–4 late toxicity in 5 of 41 patients (12%). Six patients died within 3 months after MRgRT; in one of these patients, RT attribution could not be ruled out as cause of death. The QLQ-C30 global health status remained stable from baseline to 3 months FU (70.5 at baseline, median change of +2.7 [P = 0.5]). The 1-year cumulative overall survival for the entire cohort was 67%, and that for the primary tumor group was 66%.ConclusionOnline adaptive MRgRT for (peri)pancreatic tumors on a 1.5 T MR-Linac could be delivered as planned, with low numbers of missed fractions. In addition, treatments were associated with limited grade 3–4 toxicity and a stable QoL at 3 months of FU.

Background: The role of stereotactic ablative radiation therapy (SABR) as local treatment option after chemotherapy for locally advanced pancreatic cancer (LAPC) is evolving. However adequate patient selection criteria for SABR in patients with LAPC are lacking. Methods: A prospective institutional database collected data of patients with LAPC treated with chemotherapy, mainly FOLFIRINOX, followed by SABR, which was delivered using magnetic resonance guided radiotherapy, 40 Gy in 5 fractions within two weeks. Primary endpoint was overall survival (OS). Cox regression analyses were performed to identify predictors for OS. Results: Overall, 74 patients were included, median age 66 years, 45.9% had a KPS score of ≥90. Median OS was 19.6 months from diagnosis and 12.1 months from start of SABR. Local control was 90% at one year. Multivariable Cox regression analyses identified KPS ≥90, age <70, and absence of pain prior to SABR as independent favorable predictors for OS. The rate of grade ≥3 fatigue and late gastro-intestinal toxicity was 2.7%. Conclusions: SABR is a well-tolerated treatment in patients with unresectable LAPC following chemotherapy, with better outcomes when applied in patients with higher performance score, age <70 years and absence of pain. Future randomized trials will have to confirm these findings. [ABSTRACT FROM AUTHOR]

Treatment tolerability is a significant limitation to pancreatic cancer treatment with radiotherapy due to proximity to highly radiosensitive organs and respiratory motion necessitating expanded target margins. Further, pancreatic tumors are difficult to visualize on conventional radiotherapy systems. Surrogates are often used to locate the tumor but are often inconsistent and do not provide strong positional relations throughout the respiratory cycle. This work utilizes a retrospective dataset of 45 pancreatic cancer patients treated on an MR‐Linac system with cine MRI acquired for real‐time target tracking. We investigated intra‐fraction motion of tumors and two abdominal surrogates, leading to prediction models between the tumor and surrogate. Patient specific motion evaluation and prediction models were generated from 225 cine MRI series acquired during treatment. Tumor contours were used to evaluate the pancreatic tumor motion. Linear regression and principal component analysis (PCA) based models were used to predict tumor position from the anterior‐posterior (AP) motion of the abdominal surface, the superior‐inferior (SI) motion of the diaphragm, or a combination. Models were evaluated using mean squared error (MSE) and mean absolute error (MAE). Contour analysis showed the average pancreatic tumor motion range was 7.4 ± 2.7 mm and 14.9 ± 5.8 mm in the AP and SI directions, respectively. The PCA model had MSE of 1.4 mm2 and 0.6 mm2, for the SI and AP directions, respectively, with both surrogates as inputs for the models. When only the abdomen surrogate was used, MSE was 1.3 mm2 and 0.4 mm2 in the SI and AP directions, while it was 0.4 mm2 and 1.3 mm2 when only the diaphragm surrogate was used. We evaluated intra‐fraction pancreatic tumor motion and demonstrated prediction models between the tumor and surrogate. The models calculated the pancreatic tumor position from diaphragm, abdominal, or both contours within standard pancreatic cancer target margin, and the process could be applied to other disease sites in the abdominothoracic cavity. [ABSTRACT FROM AUTHOR]

To evaluate the image quality, dosimetric properties, setup reproducibility, and planar cine motion detection of a high‐resolution brain coil and integrated stereotactic brain immobilization system that constitute a new brain treatment package (BTP) on a low‐field magnetic resonance imaging (MRI) linear accelerator (MR‐linac). Image quality of the high‐resolution brain coil was evaluated with the 17 cm diameter spherical phantom and the American College of Radiology (ACR) Large MRI Phantom. Patient imaging studies approved by the institutional review board (IRB) assisted in selecting image acquisition parameters. Radiographic and dosimetric evaluation of the high‐resolution brain coil and the associated immobilization devices was performed using dose calculations and ion chamber measurements. End‐to‐end testing was performed simulating a cranial lesion in a phantom. Inter‐fraction setup variability and motion detection tests were evaluated on four healthy volunteers. Inter‐fraction variability was assessed based on three repeat setups for each volunteer. Motion detection was evaluated using three‐plane (axial, coronal, and sagittal) MR‐cine imaging sessions, where volunteers were asked to perform a set of specific motions. The images were post‐processed and evaluated using an in‐house program. Contrast resolution of the high‐resolution brain coil is superior to the head/neck and torso coils. The BTP receiver coils have an average HU value of 525 HU. The most significant radiation attenuation (3.14%) of the BTP, occurs through the lateral portion of the overlay board where the high‐precision lateral‐profile mask clips attach to the overlay. The greatest inter‐fraction setup variability occurred in the pitch (average 1.08 degree) and translationally in the superior/inferior direction (average 4.88 mm). Three plane cine imaging with the BTP was able to detect large and small motions. Small voluntary motions, sub‐millimeter in magnitude (maximum 0.9 mm), from motion of external limbs were detected. Imaging tests, inter‐fraction setup variability, attenuation, and end‐to‐end measurements were quantified and performed for the BTP. Results demonstrate better contrast resolution and low contrast detectability that allows for better visualization of soft tissue anatomical changes relative to head/neck and torso coil systems. [ABSTRACT FROM AUTHOR]

Aims: Reirradiation of prostate cancer (PC) local recurrences represents an emerging challenge for current radiotherapy. In this context, stereotactic body radiation therapy (SBRT) allows the delivery of high doses, with curative intent. Magnetic Resonance guided Radiation Therapy (MRgRT) has shown promising results in terms of safety, feasibility and efficacy of delivering SBRT thanks to the enhanced soft tissue contrast and the online adaptive workflow. This multicentric retrospective analysis evaluates the feasibility and efficacy of PC reirradiation, using a 0.35 T hybrid MR delivery unit. Methods: Patients affected by local recurrences of PC and treated in five institutions between 2019 and 2022 were retrospectively collected. All patients had undergone previous Radiation Therapy (RT) in definitive or adjuvant setting. Re-treatment MRgSBRT was delivered with a total dose ranging from 25 to 40 Gy in 5 fractions. Toxicity according to CTCAE v 5.0 and treatment response were assessed at the end of the treatment and at follow-up. Results: Eighteen patients were included in this analysis. All patients had previously undergone external beam radiation therapy (EBRT) up to a total dose of 59.36 to 80 Gy. Median cumulative biologically effective dose (BED) of SBRT re-treatment was 213,3 Gy (103,1-560), considering an α/β of 1.5. Complete response was achieved in 4 patients (22.2%). No grade ≥ 2 acute genitourinary (GU) toxicity events were recorded, while gastrointestinal (GI) acute toxicity events occurred in 4 patients (22.2%). Conclusion: The low rates of acute toxicity of this experience encourages considering MRgSBRT a feasibile therapeutic approach for the treatment of clinically relapsed PC. Accurate gating of target volumes, the online adaptive planning workflow and the high definition of MRI treatment images allow delivering high doses to the PTV while efficiently sparing organs at risk (OARs). [ABSTRACT FROM AUTHOR]

Aim: This study aims to compare acute toxicity of prostate cancer (PCa) stereotactic body radiotherapy (SBRT) delivered by MR-guided radiotherapy (MRgRT) with 1.5-T MR-linac or by volumetric modulated arc (VMAT) with conventional linac. Methods: Patients with low-to-favorable intermediate risk class PCa were treated with exclusive SBRT (35 Gy in five fractions). Patients treated with MRgRT were enrolled in an Ethical Committee (EC) approved trial (Prot. n° 23,748), while patients treated with conventional linac were enrolled in an EC approved phase II trial (n° SBRT PROG112CESC). The primary end-point was the acute toxicity. Patients were included in the analysis if they had at least 6 months of follow-up for the primary end-point evaluation. Toxicity assessment was performed according to CTCAE v5.0 scale. International Prostatic Symptoms Score (IPSS) was also performed. Results: A total of 135 patients were included in the analysis. Seventy-two (53.3%) were treated with MR-linac and 63 (46.7%) with conventional linac. The median initial PSA before RT was 6.1 ng/ml (range 0.49–19). Globally, acute G1, G2, and G3 toxicity occurred in 39 (28.8%), 20 (14.5%), and 5 (3.7%) patients. At the univariate analysis, acute G1 toxicity did not differ between MR-linac and conventional linac (26.4% versus 31.8%), as well as G2 toxicity (12.5% versus 17.5%; p = 0.52). Acute G2 gastrointestinal (GI) toxicity occurred in 7% and 12.5% of cases in MR-linac and conventional linac group, respectively (p = 0.06), while acute G2 genitourinary toxicity occurred in 11% and 12.8% in MR-linac and conventional linac, respectively (p = 0.82). The median IPSS before and after SBRT was 3 (1–16) and 5 (1–18). Acute G3 toxicity occurred in two cases in the MR-linac and three cases in the conventional linac group (p = n.s.). Conclusion: Prostate SBRT with 1.5-T MR-linac is feasible and safe. Compared to conventional linac, MRgRT might to potentially reduce the overall G1 acute toxicity at 6 months, and seems to show a trend toward a lower incidence of grade 2 GI toxicity. A longer follow-up is necessary to assess the late efficacy and toxicity. [ABSTRACT FROM AUTHOR]

Background and purpose: 3D Magnetic Resonance Imaging (MRI) is used in radiation therapy for reference planning and, lately, for adaptive treatments on MR accelerators. This study aimed to investigate the impact of different types of respiratory motion on the apparent target position and extent in such scans. Materials and methods: An MRI motion phantom with a 30 mm diameter target was used to simulate cranial-caudal (CC) motion and imaged at an MR-Linac using a standard clinically released 3D T2w sequence. Scans were acquired for each combination of functions (sin(t), sin4(t) and sin12(t)), peak-to-peak amplitudes (5, 10, 15 and 20 mm), and periods (4, 5 and 6 s). Furthermore, respiration CC motion patterns from two patients were used. Motion functions were shifted such that the time average target position would match a static reference scan at 0-position. The target was automatically identified in coronal and sagittal images using k-means clustering. The mean position and area of the target were calculated and compared to the reference scan. Results: Artefacts increased with amplitude and depended on the motion type. Sin(t) and sin4(t) oscillations resulted in a blurring of the target, which led to an increased target area, while sin12(t) motion did not show significant changes in the target area. However, for the sin12(t) motion, the offset in apparent position was prominent, while that was not the case for the sin(t) and sin4(t) motion. The patient respiration motion profiles showed similar trends. Conclusions: In 3D MRI, target motion can change apparent tumour extent and apparent position. The changes increase with motion amplitude and depend on the motion type.

Neurovascular bundle (NVB) and internal pudendal artery (IPA) sparing during magnetic resonance-guided radiotherapy (MRgRT) for prostate cancer aims for preservation of erectile function. Our present workflow involves daily online contouring and re-planning on a 1.5 T MR-linac, as alternative to conventional (rigid) translation-only corrections of the prostate. We compared planned dose for the NVB and IPA between strategies. Total planned dose was significantly lower with daily online contouring and re-planning for the NVB, but not for the IPA. For the NVB and IPA, the intrapatient difference between highest and lowest fraction dose was significantly smaller for the contouring and re-planning plans.