Summary 205 who were treated with 5 x 7.25 Gy in two daily sub-fractions of 3.625 Gy (10 x 3.625 Gy in total). The results of this study showed that the sub-fractionation workflow positively affected the residual intrafraction prostate motion, with no 3D CTV displacement beyond 2.7 mm. Based on the standard margin recipe, the results allowed for reduction of the PTV margins from 5 mm to 2 mm (left-right and cranial-caudal) and 3 mm (anterior-posterior). The workflow is currently clinically implemented for prostate cancer SBRT treatment, as a precursor to fast, (automatic) intrafraction adaptive workflows that allow continuous target tracking and e.g. exceptional gating or multileaf collimator (MLC)-tracking. Early clinical outcomes of MRI-guided SBRT for prostate cancer To provide insight into the outcomes and effects of treatment for localised prostate cancer, all patients treated with MRI-guided radiotherapy on a 1.5 T MR-Linac at the Department of Radiation Oncology of the UMC Utrecht are asked to participate in the international MOMENTUM (‘MultiOutcoMe EvaluatioN of radiation Therapy Using the MR-Linac’) study. The MOMENTUM study is a multicentre initiative, aimed at evaluation of 1.5 T MR-Linac treatment for various indications. This also includes prostate patients treated with MRI-guided SBRT. In the prospective MOMENTUM study, patient and (technical) treatment data, as well as physician- and patient-reported outcomes, are gathered before, during, and after treatment. Additionally, for prostate cancer patients, prostatespecific antigen (PSA) measurements are performed to assess oncological outcomes. Patients who signed informed consent, are asked to fill out several domain-specific and general quality of life and symptom questionnaires at baseline and at 3, 6, 12, and 24 months post-treatment. In chapter 6, the initial results of the short and mid-term (up till 12 months post-treatment) outcomes were presented and discussed for 425 prostate cancer patients treated on an MR-Linac with 5 x 7.25 Gy using daily treatment plan optimisation. This study showed that MR-Linac SBRT treatment is generally well tolerated by patients and patient-reported outcomes were comparable to other studies reporting on outcomes after (MRI-guided) prostate cancer SBRT. Still, urinary-related symptoms – although transient – were common shortly after treatment. Furthermore, a significant proportion of patients with good erectile function at baseline, showed a significant decrease in erectile function over time. Although these initial results are very encouraging, longer follow-up and comparative – preferably randomised – studies are needed to define the real benefit of MRIguidance with respect to toxicity and oncological outcomes. Since lower grade (grade 1-2) urinary complaints are still quite common after prostate cancer SBRT in the first months following treatment, there remains room for improvement. By correlating the dose that is delivered to specific organs or (sub)structures with toxicity outcomes, we could optimise the radiotherapy treatment plan and thereby potentially lower the risk of toxicity. However, data on the association between urinary toxicity and the actual delivered dose is scarce. The data that is obtained through the MR-Linac (including the MR images and daily treatment plans) allows for precise estimation of the actual delivered dose. In chapter 7, we assessed the correlation between the accumulated dose to the bladder and bladder wall and patient-reported acute urinary toxicity. We therefore used data from the Utrecht Prostate Cohort (UPC) study. One-hundred-and-thirty prostate cancer patients treated with SBRT (5 x 7.25 Gy) on a 1.5 T MR-Linac between February 2020 10
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