The integration of magnetic resonance (MR) imaging and linear accelerators into hybrid treatment systems has made MR-guided radiation therapy a clinical reality. This work summarizes the technical design of a 0.35 T MR-Linac and corresponding clinical concepts. The system facilitates 3D-conformal as well as IMRT treatments with 6MV photons. Daily MR imaging provides superior soft-tissue contrast for patient setup and also enables on-table adaption of treatment plans, which is fully integrated into the treatment workflow of the system. Automated beam gating during delivery is facilitated by cine MR imaging and structure tracking. Combining different novel features compared to conventional image-guided radiotherapy, this technology offers the potential for margin reduction as well as dose escalation.

The clinical introduction of on-table adaptive radiotherapy with Magnetic Resonance (MR)-guided linear accelerators (Linacs) yields new challenges and potential risks. Since the adapted plan is created within a highly interdisciplinary workflow with the patient in treatment position, time pressure or erroneous communication may lead to various possibly hazardous situations. To identify risks and implement a safe workflow, a proactive risk analysis has been conducted. A process failure mode, effects and criticality analysis (P-FMECA) was performed within a group of radiation therapy technologists, physicians and physicists together with an external moderator. The workflow for on-table adaptive MR-guided treatments was defined and for each step potentially hazardous situations were identified. The risks were evaluated within the team in order to homogenize risk assessment. The team elaborated and discussed possible mitigation strategies and carried out their implementation. In total, 89 risks were identified for the entire MR-guided online adaptive workflow. After mitigation, all risks could be minimized to an acceptable level. Overall, the need for a standardized workflow, clear-defined protocols together with the need for checklists to ensure protocol adherence were identified among the most important mitigation measures. Moreover, additional quality assurance processes and automated plan checks were developed. Despite additional workload and beyond the fulfilment of legal requirements, execution of the P-FMECA within an interdisciplinary team helped all involved occupational groups to develop and foster an open culture of safety and to ensure a consensus for an efficient and safe online adaptive radiotherapy workflow.

Background: Stereotactic body radiotherapy (SBRT) is an established local treatment method for patients with hepatic oligometastasis or oligoprogression. Liver metastases often occur in close proximity to radiosensitive organs at risk (OARs). This limits the possibility to apply sufficiently high doses needed for optimal local control. Online MR-guided radiotherapy (oMRgRT) is expected to hold potential to improve hepatic SBRT by offering superior soft-tissue contrast for enhanced target identification as well as the benefit of gating and daily real-time adaptive treatment. The MAESTRO trial therefore aims to assess the potential advantages of adaptive, gated MR-guided SBRT compared to conventional SBRT at a standard linac using an ITV (internal target volume) approach. Methods: This trial is conducted as a prospective, randomized, three-armed phase II study in 82 patients with hepatic metastases (solid malignant tumor, 1–3 hepatic metastases confirmed by magnetic resonance imaging (MRI), maximum diameter of each metastasis ≤ 5 cm (in case of 3 metastases: sum of diameters ≤ 12 cm), age ≥ 18 years, Karnofsky Performance Score ≥ 60%). If a biologically effective dose (BED) ≥ 100 Gy (α/β = 10 Gy) is feasible based on ITV-based planning, patients will be randomized to either MRgRT or ITV-based SBRT. If a lesion cannot be treated with a BED ≥ 100 Gy, the patient will be treated with MRgRT at the highest possible dose. Primary endpoint is the non-inferiority of MRgRT at the MRIdian Linac® system compared to ITV-based SBRT regarding hepatobiliary and gastrointestinal toxicity CTCAE III or higher. Secondary outcomes investigated are local, locoregional (intrahepatic) and distant tumor control, progression-free survival, overall survival, possible increase of BED using MRgRT if the BED is limited with ITV-based SBRT, treatment-related toxicity, quality of life, dosimetric parameters of radiotherapy plans as well as morphological and functional changes in MRI. Potential prognostic biomarkers will also be evaluated. Discussion: MRgRT is known to be both highly cost- and labor-intensive. The MAESTRO trial aims to provide randomized, higher-level evidence for the dosimetric and possible consecutive clinical benefit of MR-guided, on-table adaptive and gated SBRT for dose escalation in critically located hepatic metastases adjacent to radiosensitive OARs. Trial registration: The study has been prospectively registered on August 30th, 2021: Clinicaltrials.gov, “Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases (MAESTRO)”, NCT05027711.

(1) Background: To assess dosimetry benefits of stereotactic magnetic resonance (MR)-guided online adaptive radiotherapy (SMART) of liver metastases. (2) Methods: This is a subgroup analysis of an ongoing prospective registry including patients with liver metastases. Patients were treated at the MRIdian Linac between February 2020 and April 2022. The baseline plan was recalculated based on the updated anatomy of the day to generate the predicted plan. This predicted plan could then be re-optimized to create an adapted plan. (3) Results: Twenty-three patients received 30 SMART treatment series of in total 36 liver metastases. Most common primary tumors were colorectal- and pancreatic carcinoma (26.1% respectively). Most frequent fractionation scheme (46.6%) was 50 Gy in five fractions. The adapted plan was significantly superior compared to the predicted plan in regard to planning-target-volume (PTV) coverage, PTV overdosing, and organs-at-risk (OAR) dose constraints violations (91.5 vs. 38.0%, 6 vs. 19% and 0.6 vs. 10.0%; each p < 0.001). Plan adaptation significantly increased median BEDD95 by 3.2 Gy (p < 0.001). Mean total duration of SMART was 72.4 min. (4) Conclusions: SMART offers individualized ablative irradiation of liver metastases tailored to the daily anatomy with significant superior tumor coverage and improved sparing of OAR.

Online adaption of treatment plans on a magnetic resonance (MR)‐Linac enables the daily creation of new (adapted) treatment plans using current anatomical information of the patient as seen on MR images. Plan quality assurance (QA) relies on a secondary dose calculation (SDC) that is required because a pretreatment measurement is impossible during the adaptive workflow. However, failure mode and effect analysis of the adaptive planning process shows a large number of error sources, and not all of them are covered by SDC. As the complex multidisciplinary adaption process takes place under time pressure, additional software solutions for pretreatment per‐fraction QA need to be used. It is essential to double‐check SDC input to ensure a safe treatment delivery. Here, we present an automated treatment plan check tool for adaptive radiotherapy (APART) at a 0.35 T MR‐Linac. It is designed to complement the manufacturer‐provided adaptive QA tool comprising SDC. Checks performed by APART include contour analysis, electron density map examinations, and fluence modulation complexity controls. For nine of 362 adapted fractions (2.5%), irregularities regarding missing slices in target volumes and organs at risks as well as in margin expansion of target volumes have been found. This demonstrates that mistakes occur and can be detected by additional QA measures, especially contour analysis. Therefore, it is recommended to implement further QA tools additional to what the manufacturer provides to facilitate an informed decision about the quality of the treatment plan.

(1) Background: Magnetic-resonance (MR)-guided stereotactic body radiotherapy (SBRT) allows for ablative, non-invasive treatment of liver metastases. However, long-term clinical outcome data are missing. (2) Methods: Patients received MR-guided SBRT with a MRIdian Linac between January 2019 and October 2021 and were part of an ongoing prospective observational registry. Local hepatic control (LHC), distant hepatic control (DHC), progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan–Meier method. Toxicity was documented according to CTCAE (v.5.0). (3) Results: Forty patients were treated for a total of 54 liver metastases (56% with online plan adaptation). Median prescribed dose was 50 Gy in five fractions equal to a biologically effective dose (BED) (alpha/beta = 10 Gy) of 100 Gy. At 1 and 2 years, LHC was 98% and 75%, DHC was 34% and 15%, PFS was 21% and 5% and OS was 83% and 57%. Two-year LHC was higher in case of BED > 100 Gy (100% vs. 57%; log-rank p = 0.04). Acute grade 1 and 2 toxicity (mostly nausea) occurred in 26% and 7% of the patients, with no grade ≥ 3 event. (4) Conclusions: To our knowledge, this is the largest cohort of MR-guided liver SBRT. Long-term local control was promising and underscores the aim of achieving >100 Gy BED. Nonetheless, distant tumor control remains challenging.