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.

The Radiation Therapy Technology Evidence Matrix: a framework to visualize evidence development for innovations in radiation therapy.

Clinical evidence is crucial in enabling the judicious adoption of technological innovations in radiation therapy (RT). Pharmaceutical evidence development frameworks are not useful for understanding how technical advances are maturing. In this paper, we introduce a new framework, the Radiation Therapy Technology Evidence Matrix (rtTEM), that helps visualize how the clinical evidence supporting new technologies is developing. The matrix is a unique 2D model based on the R-IDEAL clinical evaluation framework. It can be applied to clinical hypothesis testing trials, as well as publications reporting clinical treatment. We present the rtTEM and illustrate its application, using emerging and mature RT technologies as examples. The model breaks down the type of claim along the vertical axis and the strength of the evidence for that claim on the horizontal axis, both of which are inherent in clinical hypothesis testing. This simplified view allows for stakeholders to understand where the evidence is and where it is heading. Ultimately, the value of an innovation is typically demonstrated through superiority studies, which we have divided into three key categories - administrative, toxicity and control, to enable more detailed visibility of evidence development in that claim area. We propose the rtTEM can be used to track evidence development for new interventions in RT. We believe it will enable researchers and sponsors to identify gaps in evidence and to further direct evidence development. Thus, by highlighting evidence looked for by key policy decision makers, the rtTEM will support wider, timely patient access to high value technological advances.

A systematic review and meta-analysis of radiotherapy planning studies comparing multi leaf collimator designs.

BACKGROUND AND PURPOSE: Several studies have investigated multi leaf collimator (MLC) leaf design. We performed a systematic review and meta-analysis of those studies to compare the impact of MLC leaf width used for different radiotherapy techniques. MATERIALS AND METHODS: We decided to focus on 2.5, 3.0 and 5.0 mm leaf width MLCs as it appeared to be the most contentious area from literature. We adopted Cochrane and PRISMA guidelines and computed the association between MLC leaf width and conformity index (CI) across the selected studies as pooled mean difference (PMD) with 95% confidence interval. RESULTS: A total of 43 papers were selected from the literature search, of which ten compare MLC leaf width of 2.5 mm or 3.0 mm (MLC2.5 mm) versus 5.0 mm (MLC5 mm) in terms of CI. There was a slight, but significant, difference between MLC2.5 mm and MLC5 mm in favor of the former (mean difference -0.036; 95% confidence interval: -0.068 to -0.005). A subgroup analysis was performed by comparing techniques (intensity modulated radiation therapy vs conformal). In the intensity modulated radiation therapy (IMRT) subgroup, the difference between MLC2.5 mm and MLC5 mm appeared to be negligible (mean difference: -0.006; 95% confidence interval: -0.013 to 0.001) and not significantly different from zero. In the subgroup of studies which used conformal techniques, there was a significant difference between MLC2.5 mm and MLC5 mm (mean difference: -0.054; 95% confidence interval: -0.096 to -0.012). CONCLUSIONS: Introduction of IMRT produced comparable target coverage (CI) between 2.5 or 5.0 mm leaf width MLCs.