Safety and Tolerability of Online Adaptive High-Field Magnetic Resonance-Guided Radiotherapy.

Importance: In 2018, the first online adaptive magnetic resonance (MR)-guided radiotherapy (MRgRT) system using a 1.5-T MR-equipped linear accelerator (1.5-T MR-Linac) was clinically introduced. This system enables online adaptive radiotherapy, in which the radiation plan is adapted to size and shape changes of targets at each treatment session based on daily MR-visualized anatomy. Objective: To evaluate safety, tolerability, and technical feasibility of treatment with a 1.5-T MR-Linac, specifically focusing on the subset of patients treated with an online adaptive strategy (ie, the adapt-to-shape [ATS] approach). Design, Setting, and Participants: This cohort study included adults with solid tumors treated with a 1.5-T MR-Linac enrolled in Multi Outcome Evaluation for Radiation Therapy Using the MR-Linac (MOMENTUM), a large prospective international study of MRgRT between February 2019 and October 2021. Included were adults with solid tumors treated with a 1.5-T MR-Linac. Data were collected in Canada, Denmark, The Netherlands, United Kingdom, and the US. Data were analyzed in August 2023. Exposure: All patients underwent MRgRT using a 1.5-T MR-Linac. Radiation prescriptions were consistent with institutional standards of care. Main Outcomes and Measures: Patterns of care, tolerability, and technical feasibility (ie, treatment completed as planned). Acute high-grade radiotherapy-related toxic effects (ie, grade 3 or higher toxic effects according to Common Terminology Criteria for Adverse Events version 5.0) occurring within the first 3 months after treatment delivery. Results: In total, 1793 treatment courses (1772 patients) were included (median patient age, 69 years [range, 22-91 years]; 1384 male [77.2%]). Among 41 different treatment sites, common sites were prostate (745 [41.6%]), metastatic lymph nodes (233 [13.0%]), and brain (189 [10.5%]). ATS was used in 1050 courses (58.6%). MRgRT was completed as planned in 1720 treatment courses (95.9%). Patient withdrawal caused 5 patients (0.3%) to discontinue treatment. The incidence of radiotherapy-related grade 3 toxic effects was 1.4% (95% CI, 0.9%-2.0%) in the entire cohort and 0.4% (95% CI, 0.1%-1.0%) in the subset of patients treated with ATS. There were no radiotherapy-related grade 4 or 5 toxic effects. Conclusions and Relevance: In this cohort study of patients treated on a 1.5-T MR-Linac, radiotherapy was safe and well tolerated. Online adaptation of the radiation plan at each treatment session to account for anatomic variations was associated with a low risk of acute grade 3 toxic effects.

Dynamic recurrent inference machines for accelerated MRI-guided radiotherapy of the liver.

Recurrent inference machines (RIM), a deep learning model that learns an iterative scheme for reconstructing sparsely sampled MRI, has been shown able to perform well on accelerated 2D and 3D MRI scans, learn from small datasets and generalize well to unseen types of data. Here we propose the dynamic recurrent inference machine (DRIM) for reconstructing sparsely sampled 4D MRI by exploiting correlations between respiratory states. The DRIM was applied to a 4D protocol for MR-guided radiotherapy of liver lesions based on repetitive interleaved coronal 2D multi-slice T2-weighted acquisitions. We demonstrate with an ablation study that the DRIM outperforms the RIM, increasing the SSIM score from about 0.89 to 0.95. The DRIM allowed for an approximately 2.7 times faster scan time than the current clinical protocol with only a slight loss in image sharpness. Correlations between slice locations can also be used, but were found to be of less importance, as were a majority of tested variations in network architecture, as long as the respiratory states are processed by the network. Through cross-validation, the DRIM is also shown to be robust in terms of training data. We further demonstrate a good performance across a large range of subsampling factors, and conclude through an evaluation by a radiation oncologist that reconstructed images of the liver contour and inner structures are of a clinically acceptable standard at acceleration factors 10x and 8x, respectively. Finally, we show that binning the data with respect to respiratory states prior to reconstruction comes at a slight cost to reconstruction quality, but at greater speed of the overall protocol.

Longitudinal Correlations Between Intravoxel Incoherent Motion (IVIM) and Dynamic Contrast-Enhanced (DCE) MRI During Radiotherapy in Prostate Cancer Patients.

Purpose: Intravoxel incoherent motion (IVIM) is a promising technique that can acquire perfusion information without the use of contrast agent, contrary to the more established dynamic contrast-enhanced (DCE) technique. This is of interest for treatment response monitoring, where patients can be imaged on each treatment fraction. In this study, longitudinal correlations between IVIM- and DCE parameters were assessed in prostate cancer patients receiving radiation treatment. Materials and Methods: 20 prostate cancer patients were treated on a 1.5 T MR-linac with 20 x 3 or 3.1 Gy. Weekly IVIM and DCE scans were acquired. Tumors, the peripheral zone (PZ), and the transition zone (TZ) were delineated on a T2-weighted scan acquired on the first fraction. IVIM and DCE scans were registered to this scan and the delineations were propagated. Median values from these delineations were used for further analysis. The IVIM parameters D, f, D* and the product fD* were calculated. The Tofts model was used to calculate the DCE parameters Ktrans, kep and ve. Pearson correlations were calculated for the IVIM and DCE parameters on values from the first fraction for each region of interest (ROI). For longitudinal analysis, the repeated measures correlation coefficient was used to determine correlations between IVIM and DCE parameters in each ROI. Results: When averaging over patients, an increase during treatment in all IVIM and DCE parameters was observed in all ROIs, except for D in the PZ and TZ. No significant Pearson correlations were found between any pair of IVIM and DCE parameters measured on the first fraction. Significant but low longitudinal correlations were found for some combinations of IVIM and DCE parameters in the PZ and TZ, while no significant longitudinal correlations were found in the tumor. Notably in the TZ, for both f and fD*, significant longitudinal correlations with all DCE parameters were found. Conclusions: The increase in IVIM- and DCE parameters when averaging over patients indicates a measurable response to radiation treatment with both techniques. Although low, significant longitudinal correlations were found which suggests that IVIM could potentially be used as an alternative to DCE for treatment response monitoring.

First multicentre experience of SABR for lymph node and liver oligometastatic disease on the unity MR-Linac.

The treatment of oligometastatic disease using MR guidance is an evolving field. Since August 2018 patients are treated on a 1.5 Tesla MR-Linac (MRL). We present current workflows and practice standards from seven institutions for the initial patients treated for lymph node and liver metastases.

Daily Intravoxel Incoherent Motion (IVIM) In Prostate Cancer Patients During MR-Guided Radiotherapy-A Multicenter Study.

PURPOSE: Daily quantitative MR imaging during radiotherapy of cancer patients has become feasible with MRI systems integrated with linear accelerators (MR-linacs). Quantitative images could be used for treatment response monitoring. With intravoxel incoherent motion (IVIM) MRI, it is possible to acquire perfusion information without the use of contrast agents. In this multicenter study, daily IVIM measurements were performed in prostate cancer patients to identify changes that potentially reflect response to treatment. MATERIALS AND METHODS: Forty-three patients were included, treated with 20 fractions of 3 Gy on a 1.5 T MR-linac. IVIM measurements were performed on each treatment day. The diffusion coefficient (D), perfusion fraction (f), and pseudo-diffusion coefficient (D*) were calculated based on the median signal intensities in the non-cancerous prostate and the tumor. Repeatability coefficients (RCs) were determined based on the first two treatment fractions. Separate linear mixed-effects models were constructed for the three IVIM parameters. RESULTS: In total, 726 fractions were analyzed. Pre-treatment average values, measured on the first fraction before irradiation, were 1.46 × 10-3 mm2/s, 0.086, and 28.7 × 10-3 mm2/s in the non-cancerous prostate and 1.19 × 10-3 mm2/s, 0.088, and 28.9 × 10-3 mm2/s in the tumor, for D, f, and D*, respectively. The repeatability coefficients for D, f, and D* in the non-cancerous prostate were 0.09 × 10-3 mm2/s, 0.05, and 15.3 × 10-3 mm2/s. In the tumor, these values were 0.44 × 10-3 mm2/s, 0.16, and 76.4 × 10-3 mm2/s. The mixed effects analysis showed an increase in D of the tumors over the course of treatment, while remaining stable in the non-cancerous prostate. The f and D* increased in both the non-cancerous prostate and tumor. CONCLUSIONS: It is feasible to perform daily IVIM measurements on an MR-linac system. Although the repeatability coefficients were high, changes in IVIM perfusion parameters were measured on a group level, indicating that IVIM has potential for measuring treatment response.

Patterns of Care, Tolerability, and Safety of the First Cohort of Patients Treated on a Novel High-Field MR-Linac Within the MOMENTUM Study: Initial Results From a Prospective Multi-Institutional Registry.

PURPOSE: High-field magnetic resonance-linear accelerators (MR-Linacs), linear accelerators combined with a diagnostic magnetic resonance imaging (MRI) scanner and online adaptive workflow, potentially give rise to novel online anatomic and response adaptive radiation therapy paradigms. The first high-field (1.5T) MR-Linac received regulatory approval in late 2018, and little is known about clinical use, patient tolerability of daily high-field MRI, and toxicity of treatments. Herein we report the initial experience within the MOMENTUM Study (NCT04075305), a prospective international registry of the MR-Linac Consortium. METHODS AND MATERIALS: Patients were included between February 2019 and October 2020 at 7 institutions in 4 countries. We used descriptive statistics to describe the patterns of care, tolerability (the percentage of patients discontinuing their course early), and safety (grade 3-5 Common Terminology Criteria for Adverse Events v.5 acute toxicity within 3 months after the end of treatment). RESULTS: A total 943 patients participated in the MOMENTUM Study, 702 of whom had complete baseline data at the time of this analysis. Patients were primarily male (79%) with a median age of 68 years (range, 22-93) and were treated for 39 different indications. The most frequent indications were prostate (40%), oligometastatic lymph node (17%), brain (12%), and rectal (10%) cancers. The median number of fractions was 5 (range, 1-35). Six patients discontinued MR-Linac treatments, but none due to an inability to tolerate repeated high-field MRI. Of the 415 patients with complete data on acute toxicity at 3-month follow-up, 18 (4%) patients experienced grade 3 acute toxicity related to radiation. No grade 4 or 5 acute toxicity related to radiation was observed. CONCLUSIONS: In the first 21 months of our study, patterns of care were diverse with respect to clinical utilization, body sites, and radiation prescriptions. No patient discontinued treatment due to inability to tolerate daily high-field MRI scans, and the acute radiation toxicity experience was encouraging.

Development and results of a patient-reported treatment experience questionnaire on a 1.5 T MR-Linac.

INTRODUCTION: With the implementation of new radiotherapy technology, it is imperative that patient experience is investigated alongside efficacy and outcomes. This paper presents the development of a specifically designed validated questionnaire and a first report of international multi-institutional preliminary patient experience of MRI-guided adaptive radiotherapy (MRgART) on the 1.5 T MR-Linac (MRL). METHODS: A patient experience questionnaire was developed and validated before being distributed to the Elekta MRL Consortium, to gather first patient-reported experience from participating centres worldwide. The final version of the questionnaire contains 18 questions covering a range of themes and was scored on a Likert scale of 0-3. Responses were post-processed so that a score of 0 represents a negative response and 3 represents the most favourable response. These results were analysed for patient-reported experience of treatment on the MRL. Results were also analysed for internal consistency of the questionnaire using Chronbach's Alpha and the questionnaire contents were validated for relevance using content validity indexes (CVI). RESULTS: 170 responses were received from five centres, representing patients with a wide range of tumour treatment sites from four different countries. MRgART was well tolerated with an 84% favourable response across all questions and respondents. When analysed by theme, all reported the highest percentage of results in the favourable categories (2 and 3). Internal consistency in the questionnaire was high (Cronbach's α = 0.8) and the item-level CVI for each question was 0.78 or above and the Scale-level CVI was 0.93, representing relevant content. CONCLUSION: The developed questionnaire has been validated as relevant and appropriate for use in reporting experience of patients undergoing treatment on the MRL. The overall patient-reported experience and satisfaction from multiple centres within the Elekta MRL Consortium was consistently high. These results can reinforce user confidence in continuing to expand and develop MRL use in adaptive radiotherapy.

Validation of a 4D-MRI guided liver stereotactic body radiation therapy strategy for implementation on the MR-linac.

Purpose. Accurate tumor localization for image-guided liver stereotactic body radiation therapy (SBRT) is challenging due to respiratory motion and poor tumor visibility on conventional x-ray based images. Novel integrated MRI and radiotherapy systems enable direct in-room tumor visualization, potentially increasing treatment accuracy. As these systems currently do not provide a 4D image-guided radiotherapy strategy, we developed a 4D-MRI guided liver SBRT workflow and validated all steps for implementation on the Unity MR-linac.Materials and Methods. The proposed workflow consists of five steps: (1) acquisition of a daily 4D-MRI scan, (2) 4D-MRI to mid-position planning-CT rigid tumor registration, (3) calculation of daily tumor midP misalignment, (4) plan adaptation using adapt-to-position (ATP) with segment-weights optimization and (5) adapted plan delivery. The workflow was first validated in a motion phantom, performing regular motion at different baselines (±5 to ±10 mm) and patient-derived respiratory signals with varying degrees of irregularity. 4D-MRI derived respiratory signals and 4D-MRI to planning CT registrations were compared to the phantom input, and gamma and dose-area-histogram analyses were performed on the delivered dose distributions on film. Additionally, 4D-MRI to CT registration performance was evaluated in patient images using the full-circle method (transitivity analysis). Plan adaption was further analyzedin-silicoby creating adapted treatment plans for 15 patients with oligometastatic liver disease.Results. Phantom trajectories could be reliably extracted from 4D-MRI scans and 4D-MRI to CT registration showed submillimeter accuracy. The DAH-analysis demonstrated excellent coverage of the dose evaluation structures GTV and GTVTD. The median daily rigid 4D-MRI to midP-CT registration precision in patient images was <2 mm. The ATP strategy restored the target dose without increased exposure to the OARs and plan quality was independent from 3D shift distance in the range of 1-26 mm.Conclusions. The proposed 4D-MRI guided strategy showed excellent performance in all workflow tests in preparation of the clinical introduction on the Unity MR-linac.

Automatic dosimetric verification of online adapted plans on the Unity MR-Linac using 3D EPID dosimetry.

BACKGROUND AND PURPOSE: The Unity MR-Linac is equipped with an EPID, the images from which contain information about the dose delivered to the patient. The purpose of this study was to introduce a framework for the automatic dosimetric verification of online adapted plans using 3D EPID dosimetry and to present the obtained dosimetric results. MATERIALS AND METHODS: The framework was active during the delivery of 1207 online adapted plans corresponding to 127 clinical IMRT treatments (74 prostate, 19 rectum, 19 liver and 15 lymph node oligometastases). EPID reconstructed dose distributions in the patient geometry were calculated automatically and then compared to the dose distributions calculated online by the treatment planning system (TPS). The comparison was performed by γ-analysis (3% global/2mm/10% threshold) and by the difference in median dose to the high-dose volume (ΔHDVD50). 85% for γ-pass rate and 5% for ΔHDVD50 were used as tolerance limit values. RESULTS: 93% of the online plans were verified automatically by the framework. Missing EPID data was the reason for automation failure. 91% of the verified plans were within tolerance. CONCLUSION: Automatic dosimetric verification of online adapted plans on the Unity MR-Linac is feasible using in vivo 3D EPID dosimetry. Almost all online adapted plans were approved automatically by the framework. This newly developed framework is a major step forward towards the clinical implementation of a permanent safety net for the entire online adaptive workflow.

Pre-treatment prediction of early response to chemoradiotherapy by quantitative analysis of baseline staging FDG-PET/CT and MRI in locally advanced cervical cancer.

BACKGROUND: Early prediction of response to concurrent chemoradiotherapy (cCRT) could aid to further optimize treatment regimens for locally advanced cervical cancer (LACC) in the future. PURPOSE: To explore whether quantitative parameters from baseline (pre-therapy) magnetic resonance imaging (MRI) and FDG-PET/computed tomography (CT) have potential as predictors of early response to cCRT. MATERIAL AND METHODS: Forty-six patients with LACC undergoing cCRT after staging with FDG-PET/CT and MRI were retrospectively analyzed. Primary tumor volumes were delineated on FDG-PET/CT, T2-weighted (T2W)-MRI and diffusion-weighted MRI (DWI) to extract the following quantitative parameters: T2W volume; T2W signalmean; DWI volume; ADCmean; ADCSD; MTV42%; and SUVmax. Outcome was the early treatment response, defined as the residual tumor volume on MRI 3-4 weeks after start of external beam radiotherapy with chemotherapy (before the start of brachytherapy): patients with a residual tumor volume <10 cm3 were classified as early responders. Imaging parameters were analyzed together with FIGO stage to assess their performance to predict early response, using multivariable logistic regression analysis with bi-directional variable selection. Leave-one-out cross-validation with bootstrapping was used to simulate performance in a new, independent dataset. RESULTS: T2W volume (OR 0.94, P = 0.003) and SUVmax (OR 1.15, P = 0.18) were identified as independent predictors in multivariable analysis, rendering a model with an AUC of 0.82 in the original dataset, and AUC of 0.68 (95% CI 0.41-0.81) from cross-validation. CONCLUSION: Although the predictive performance achieved in this small exploratory dataset was limited, these preliminary data suggest that parameters from baseline MRI and FDG-PET/CT (in particular pre-therapy tumor volume) may contribute to prediction of early response to cCRT in cervical cancer.

The MOMENTUM Study: An International Registry for the Evidence-Based Introduction of MR-Guided Adaptive Therapy.

Purpose: MR-guided Radiation Therapy (MRgRT) allows for high-precision radiotherapy under real-time MR visualization. This enables margin reduction and subsequent dose escalation which may lead to higher tumor control and less toxicity. The Unity MR-linac (Elekta AB, Stockholm, Sweden) integrates a linear accelerator with a 1.5T diagnostic quality MRI and an online adaptive workflow. A prospective international registry was established to facilitate the evidence-based implementation of the Unity MR-linac into clinical practice, to systemically evaluate long-term outcomes, and to aid further technical development of MR-linac-based MRgRT. Methods and Results: In February 2019, the Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac study (MOMENTUM) started within the MR-linac Consortium. The MOMENTUM study is an international academic-industrial partnership between several hospitals and industry partner Elekta. All patients treated on the MR-linac are eligible for inclusion in MOMENTUM. For participants, we collect clinical patient data (e.g., patient, tumor, and treatment characteristics) and technical patient data which is defined as information generated on the MR-linac during treatment. The data are captured, pseudonymized, and stored in an international registry at set time intervals up to two years after treatment. Patients can choose to provide patient-reported outcomes and consent to additional MRI scans acquired on the MR-linac. This registry will serve as a data platform that supports multicenter research investigating the MR-linac. Rules and regulations on data sharing, data access, and intellectual property rights are summarized in an academic-industrial collaboration agreement. Data access rules ensure secure data handling and research integrity for investigators and institutions. Separate data access rules exist for academic and industry partners. This study is registered at ClinicalTrials.gov with ID: NCT04075305 (https://clinicaltrials.gov/ct2/show/NCT04075305). Conclusion: The multi-institutional MOMENTUM study has been set up to collect clinical and technical patient data to advance technical development, and facilitate evidenced-based implementation of MR-linac technology with the ultimate purpose to improve tumor control, survival, and quality of life of patients with cancer.

ADC measurements on the Unity MR-linac - A recommendation on behalf of the Elekta Unity MR-linac consortium.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) for treatment response monitoring is feasible on hybrid magnetic resonance linear accelerator (MR-linac) systems. The MRI scanner of the Elekta Unity system has an adjusted design compared to diagnostic scanners. We investigated its impact on measuring the DWI-derived apparent diffusion coefficient (ADC) regarding three aspects: the choice of b-values, the spatial variation of the ADC, and scanning during radiation treatment. The aim of this study is to give recommendations for accurate ADC measurements on Unity systems. MATERIALS AND METHODS: Signal-to-noise ratio (SNR) measurements with increasing b-values were done to determine the highest bvalue that can be measured reliably. The spatial variation of the ADC was assessed on six Unity systems with a cylindrical phantom of 40 cm diameter. The influence of gantry rotation and irradiation was investigated by acquiring DWI images before and during treatment of 11 prostate cancer patients. RESULTS: On the Unity system, a maximum b-value of 500 s/mm2 should be used for ADC quantification, as a trade-off between SNR and diffusion weighting. Accurate ADC values were obtained within 7 cm from the iso-center, while outside this region ADC values deviated more than 5%. The ADC was not influenced by the rotating linac or irradiation during treatment. CONCLUSION: We provide Unity system specific recommendations for measuring the ADC. This will increase the consistency of ADC values acquired in different centers on the Unity system, enabling large cohort studies for biomarker discovery and treatment response monitoring.

PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer.

BACKGROUND: Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients' risk of recurrence based on molecular tumor characteristics. PRIMARY OBJECTIVES: To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy STUDY HYPOTHESIS: Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs. TRIAL DESIGN: A multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm). MAJOR INCLUSION/EXCLUSION CRITERIA: Women aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1). ENDPOINTS: The primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs. SAMPLE SIZE: 500 eligible and evaluable patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Estimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025).

3D dosimetric verification of unity MR-linac treatments by portal dosimetry.

PURPOSE AND BACKGROUND: 3D dosimetric verification of online adaptive workflows is essential as their complexity is unprecedented in radiation oncology. The aim of this work is to demonstrate the feasibility of back-projection portal dosimetry for 3D dosimetric verification of Unity MR-linac treatments. MATERIAL AND METHODS: An earlier presented 2D back-projection algorithm for the Unity MR-linac geometry was extended for 3D dose reconstruction and comparison against planned dose distributions. 'In-air' as well as in-vivo portal EPID images can be used as input. The method was validated using data from treatments of 5 patients (2 rectal, 2 prostate cancer and one oligo metastasis). 3D pre-treatment verification of the reference plan using 'in-air' EPID images was performed and compared against measured (with the Octavius 4D system) and planned (in the planning CT) dose distributions. In-vivo EPID dose distributions were compared to the TPS for the first three adaptations of all treatments. For all comparisons, dose difference values at the reference point and γ-parameters were reported. RESULTS: The comparison against the OCTAVIUS 4D system (3%, 2 mm, local) showed y-mean = 0.52 ± 0.10 and y-passrate = 91.9%, 95% CI [85.4, 98.4], and ΔDRP = -0.1 ± 1.1%. Pre-treatment verification against TPS data (3%, 2 mm, global) showed y-mean = 0.52 ± 0.04, y-passrate = 93.5%, 95% CI [92.4, 94.6] and ΔDRP = -0.9 ± 1.5%. The averaged y-results for the in-vivo 3D verification were y-mean = 0.52 ± 0.05, y-passrate = 92.5%, 95% CI [90.2, 94.8] and ΔDRP = 0.8 ± 2.1%. CONCLUSION: 3D dosimetric verification of Unity MR-linac treatments using portal dosimetry is feasible, pre-treatment as well as in-vivo.

MRI-Based Upper Abdominal Organs-at-Risk Atlas for Radiation Oncology.

PURPOSE: The purpose of our study was to provide a guide for identification and contouring of upper abdominal organs-at-risk (OARs) in the setting of online magnetic resonance imaging (MRI)-guided radiation treatment planning and delivery. METHODS AND MATERIALS: After a needs assessment survey, it was determined that an upper abdominal MRI-based atlas of normal OARs would be of benefit to radiation oncologists and radiation therapists. An anonymized diagnostic 1.5T MRI from a patient with typical upper abdominal anatomy was used for atlas development. Two MRI sequences were selected for contouring, a T1-weighted gadoxetic acid contrast-enhanced MRI acquired in the hepatobiliary phase and axial fast imaging with balanced steady-state precession. Two additional clinical MRI sequences from commercial online MRI-guided radiation therapy systems were selected for contouring and were included in the final atlas. Contours from each data set were completed and reviewed by radiation oncologists, along with a radiologist who specializes in upper abdominal imaging, to generate a consensus upper abdominal MRI-based OAR atlas. RESULTS: A normal OAR atlas was developed, including recommendations for contouring. The atlas and contouring guidance are described, and high-resolution MRI images and contours are displayed. OARs, such as the bile duct and biliary tree, which may be better seen on MRI than on computed tomography, are highlighted. The full DICOM/DICOM-RT MRI images from both the diagnostic and clinical online MRI-guided radiation therapy systems data sets have been made freely available, for educational purposes, at econtour.org. CONCLUSIONS: This MRI contouring atlas for upper abdominal OARs should provide a useful reference for contouring and education. Its routine use may help to improve uniformity in contouring in radiation oncology planning and OAR dose calculation. Full DICOM/DICOM-RT images are available online and provide a valuable educational resource for upper abdominal MRI-based radiation therapy planning and delivery.

High versus low dose Stereotactic Body Radiation Therapy for hepatic metastases.

INTRODUCTION: Stereotactic Body Radiation Therapy (SBRT) is a treatment option for patients with liver metastases. This study evaluated the impact of high versus low dose image-guided SBRT of hepatic metastases. METHODS AND MATERIALS: This is a single-center retrospective study of patients with liver metastases treated with SBRT. For analyses, patients were divided into two groups: ≤100 Gy and >100 Gy near-minimum Biological Effective Doses (BED98%). The main outcomes were local control (LC), toxicity and overall survival (OS). Cox regression analyses were performed to determine prognostic variables on LC and OS. RESULTS: Ninety patients with 97 liver metastases (77% colorectal) were included. Median follow-up was 28.6 months. The two-year LC rates in the ≤100 Gy and >100 Gy BED98% group were 60% (CI: 41-80%) and 90% (CI: 80-100%), respectively (p = 0.004). Grade 3 toxicity occurred in 7% vs 2% in the ≤100 Gy and >100 Gy group (p = 0.23). Two-year OS rates in the ≤100 Gy and >100 Gy group were 48% (CI: 32-65%) and 85% (CI: 73-97%), respectively (p = 0.007). In multivariable Cox regression analyses, group dose and tumor volume were significantly correlated with LC (HR: 3.61; p = 0.017 and HR: 1.01; p = 0.005) and OS (HR: 2.38; p = 0.005 and HR: 1.01; p = <0.0001). CONCLUSION: High dose SBRT provides significantly better local control and overall survival than low dose SBRT without increasing toxicity. When surgical resection is not feasible, high dose SBRT provides an effective and safe treatment for liver metastases.

Gross Tumor Delineation in Esophageal Cancer on MRI Compared With 18F-FDG-PET/CT.

PURPOSE: Current delineation of the gross tumor volume (GTV) in esophageal cancer relies on computed tomography (CT) and combination with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). There is increasing interest in integrating magnetic resonance imaging (MRI) in radiation treatment, which can potentially obviate CT- or FDG-PET/CT-based delineation. The aim of this study is to evaluate the feasibility of target delineation on T2-weighted (T2W) MRI and T2W including diffusion-weighted MRI (T2W + DW-MRI) compared with current-practice FDG-PET/CT. METHODS: Ten observers delineated primary esophageal tumor GTVs of 6 patients on FDG-PET/CT, T2W-MRI, and T2W + DW-MRI. GTVs, generalized conformity indices, in-slice delineation variation (root mean square), and standard deviations in the position of the most cranial and caudal delineated slice were calculated. RESULTS: Delineations on MRI showed smaller GTVs compared with FDG-PET/CT-based delineations. The main variation was seen at the cranial and caudal border. No differences were observed in conformity indices (FDG-PET/CT, 0.68; T2W-MRI, 0.66; T2W + DW-MRI, 0.68) and in-slice variation (root mean square, 0.13 cm on FDG-PET/CT; 0.10 cm on T2W-MRI; 0.14 cm on T2W + DW-MRI). In the 2 tumors involving the gastroesophageal junction, addition of DW-MRI to T2W-MRI significantly decreased caudal border variation. CONCLUSIONS: MRI-based target delineation of the esophageal tumor is feasible with interobserver variability comparable to that with FDG-PET/CT, despite limited experience with delineation on MRI. Most variation was seen at cranial-caudal borders, and addition of DW-MRI to T2W-MRI may reduce caudal delineation variation of gastroesophageal junction tumors.

Investigating the impact of patient arm position in an MR-linac on liver SBRT treatment plans.

PURPOSE: The superior soft-tissue contrast offered by the integrated magnetic resonance imaging (MRI) of the Unity MR-linac compared to the x-ray-based image guidance on conventional linacs potentially allows for liver stereotactic body radiation therapy (SBRT) without the need for implanted markers or other surrogates. On conventional linacs, liver SBRT patients are typically positioned with their arms above their heads (arms-up) to minimize exposure to healthy tissue. However, the spatial confinement of the MRI-bore and increased treatment delivery times can make the arms-up position straining. Therefore, we assessed the plan quality for MR-linac treatment plans with the patient in the arms-up and in the arms-down position. Additionally, we compared the MR-linac plans with clinically used arms-up treatment plans made for a conventional linac. METHODS: Fifteen consecutively treated patients with oligometastatic liver disease were included in this retrospective study. For each patient, a planning computed tomography (CT) with delineations, a diagnostic MRI, and a 3 × 20 Gy dual-arc volumetric modulated arc therapy (VMAT) plan, which was used to treat the patient in an arms-up position on the conventional linac, were available. For the MR-linac, 15-beam step-and-shoot intensity-modulated radiation therapy (IMRT) plans were created for four patient positioning scenarios: arms-up, mimicking current clinical practice; arms-down, with treatment beams avoiding the arms on the entrance side; arms-through, arms are down but not avoided, and right-arm-up; only the right arm is up and the left arm is avoided on the entrance side. Resulting treatment plans were compared. Bonferroni-corrected two-sided Wilcoxon signed-ranks tests were used to assess statistical significance (P < 0.05). RESULTS: No significant differences were found in gross tumour volume (GTV) coverage (D 2 % , D 50 % , and D 98 % ) or liver sparing (liver-GTV V < 15 Gy ) between the clinical plans and any of the MR-linac plans. The median target conformity [exterior V 40 % /planning target volume (PTV)] was significantly better in the clinical plans (5.8) than in the MR-linac scenarios (arms-down: 6.6, arms-up/right-arm-up: 6.2, arms-through: 6.3). No MR-linac plan violated any additional organ-at-risk (OAR) constraint that was not already violated in the clinical plans. In the arms-down scenario a significantly increased median spinal cord D 1 % (14.5 Gy) was detected compared to the clinical setup (7.2 Gy). For the arms-down (arms-through) scenario, the median left arm D 1 % was 1.5 (2.7) Gy, the median right arm D 1 % was 5.8 (22.7) Gy, and the median right arm V 20 Gy was 0.0 (14.7) cc. These differences were statistically significant. For the right-arm-up scenario, the median left arm D 1 % (2.3 Gy) and V 5 Gy (0.0) were not significantly different compared to the arms-down scenario. CONCLUSIONS: Mimicking the current clinical practice by treating patients in the arms-up/right-arm-up position on the MR-linac leads to plans which are dosimetrically very similar to the conventional linac plans. Treating in the arms-down position is expected to increase patient comfort at the cost of a small reduction in OAR sparing for individual patients. Treating through the arms is not encouraged due to substantial dose deposition in the arms.

MRI basics for radiation oncologists.

MRI is increasingly used in radiation oncology to facilitate tumor and organ-at-risk delineation and image guidance. In this review, we address issues of MRI that are relevant for radiation oncologists when interpreting MR images offered for radiotherapy. Whether MRI is used in combination with CT or in an MRI-only workflow, it is generally necessary to ensure that MR images are acquired in treatment position, using the positioning and fixation devices that are commonly applied in radiotherapy. For target delineation, often a series of separate image sets are used with distinct image contrasts, acquired within a single exam. MR images can suffer from image distortions. While this can be avoided with dedicated scan protocols, in a diagnostic setting geometrical fidelity is less relevant and is therefore less accounted for. Since geometrical fidelity is of utmost importance in radiation oncology, it requires dedicated scan protocols. The strong magnetic field of an MRI scanner and the use of radiofrequency radiation can cause safety hazards if not properly addressed. Safety screening is crucial for every patient and every operator prior to entering the MRI room.