Clinical application of a sub-fractionation workflow 97 Software components To enable this sub-fractionation workflow, several features of to the commercially available software for the Elekta Unity MR-Linac were used and extended. After approval and import of the initial daily treatment plan into the patient data management system MOSAIQ® (Elekta Inc., Sunnyvale, California, USA), the online treatment planning software Monaco does allow the optimisation of a new treatment plan in the same session. However, the treatment session manager (TSM) does not allow a second treatment plan to be imported into the patient data management system MOSAIQ. The so-called ‘JamTool’ was developed in-house to enable the import of a second treatment plan from Monaco into MOSAIQ. In short, JamTool moves the dicom file generated by the Monaco treatment planning system to the import directory of MOSAIQ and ensures that the identifiers (IDs) inspected by MOSAIQ are consistent with the current TSM session. The ‘jam’ procedure is triggered by an operator via a graphical user interface and is executed within 2 sec. The JamTool software runs on a Windows-based PC within the MR-Linac treatment environment. JamTool was developed in accordance with the EuropeanMedical Device Regulation (MDR) within a dedicated software quality management system. Clinical application, feasibility and intrafraction motion assessment The workflow was clinically applied in 15 patients with low- or intermediate-risk prostate cancer, who were treated on an MR-Linac with 5 x 7.25 Gy over the course of 2.5 weeks. Patients were registered as part of an institutional review board approved registration and imaging study. Each fraction was divided into two sub-fractions (Figure 1), thus delivering 2 x 3.625 Gy each treatment session. Each first half was delivered using the previously described clinical workflow at the UMC Utrecht during which an interfraction correction is applied to correct translations, rotations, and deformations of the target and OARs (i.e. ATS procedure followed by an ATP procedure prior to beam-on) (Figure 1, steps 1-5).17 The second half was delivered following an ATP procedure using the PV2 scan (acquired simultaneously with delivery of the first plan), correcting for translations only (steps 6-8). For each sub-fraction, a new treatment plan is created that complies with the DVH constraints, thereby discarding the need for dose accumulation. The constraints used for treatment planning and MRI parameters are displayed in Table S1 and S2 (Supplementary A). No standardised bladder filling protocol was applied in these patients. All treatment sessions, including individual workflow steps, were timed. Feasibility was arbitrarily defined as being able to deliver two sequential sub-fractions in £ 60 min on-table time in ³ 95% of the fractions. The 60 min cut-off was arbitrarily chosen: this is approximately 15 min longer than the average time needed with the current workflow, but still results in a feasible one-hour timeslot that is often used for MR-Linac treatments at our department.17 Residual intrafraction Clinical Target Volume (CTV) displacement in three translation directions were estimated from the four intrafraction MRI scans obtained during a single fraction (PRE, PV1, PV2, and INTRA). Rigid registration of the CTV among these scans was performed using in-house software (Volumetool®18) with visual inspection and manual fine-tuning. Additionally, the residual 3D 5
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