Clinical application of a sub-fractionation workflow 101 Discussion In this work, we have proposed and clinically applied a sub-fractionation workflow for MRI-guided radiotherapy treatment on a 1.5 T MR-Linac system. The workflow is an adaptation of the previously routine clinical Unity system workflow. A treatment fraction is delivered in two sub-fractions within a single treatment session by performing several processes in parallel. The overall workflow is technically and clinically feasible within a timeframe very similar to the routine workflow. Furthermore, for prostate cancer SBRT, the workflow allows for PTV margin reduction based on the reduced intrafraction translational motion. To be able to progress to extremely hypofractionated radiotherapy with high fractional doses, one preferably can counteract all intrafraction motion occurring during beam-on. However, intrafraction adaptation methods are currently not clinically implemented on Unity MR-Linac systems, partly due to challenges with real-time dose accumulation. Fully, online adaptive workflows with real-time plan adaptation are the ultimate goal, but are considered by some to currently still be a far stretch.4 To start on this route, we aimed to provide a less challenging workflow for tackling intrafraction motion during SBRT, thereby bridging the gap between current interfraction-only and future fully intrafraction adaptive workflows for MRI-guided radiotherapy.21 By keeping the dose for one subfractionation cycle low, beam-on times are kept reasonably short. In our cohort of 15 patients, the total beam-on time was 11 min on average, so approximately 5.5 min per 3.625 Gy. This is very Figure 4 – Cumulative frequency (%) of residual 3D intrafraction CTV displacement in bins of 1 mm (i.e. 1.0 indicates that the 3D displacement was between 1.0-1.9 mm) with the sub-fractionation workflow (1xATS + 2xATP), previously applied workflow (1xATS + 1xATP, both lower and upper limit), and ATS-only workflow. Legend: ATS = Adapt-to-Shape. ATP = Adapt-to-Position. 5
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