General introduction and thesis outline 25 simultaneously with dose delivery. In chapter 5, the workflow is tested in 15 prostate cancer patients and the effects on intrafraction prostate motion and required error margins are assessed and discussed. At the moment of writing this thesis, more than 650 prostate cancer patients treated with SBRT on a 1.5 T MR-Linac have been included in the MOMENTUM study. In chapter 6, the initial 12-month outcomes are presented for patients treated with MRI-guided SBRT (5 x 7.25 Gy) on a 1.5 T MR-Linac using daily imaging and treatment plan optimisation. PSA kinetics, physician-reported toxicity, and patient-reported outcomes were analysed in the first 425 patients. These results provide early insight into the short-term outcomes of MRI-guided prostate cancer SBRT and can be used to guide further research. Toxicity after radiotherapy can have significant, detrimental effects on quality of life. Since lowergrade (grade 1-2) urinary toxicity is 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 outcomes (toxicity), we can potentially improve the radiotherapy plan to lower the risk of toxicity. However, data on the association between toxicity and the actual delivered dose is scarce. The data that is obtained through MR-Linac systems (including images and daily treatment plans) allows for a precise estimation of the actual delivered dose. In chapter 7, we assess the correlation between the accumulated dose received by the bladder and bladder wall and patient-reported acute urinary toxicity, and we propose new bladder (wall) dose constraints. In part II of this thesis, MRI-guided radiotherapy treatment for locally recurrent prostate cancer after primary radiotherapy is discussed. Although the toxicity rates after MRI-guided FS-HDR-BT seemvery favourable, biochemical failure after treatment occurs frequently and often within two years after treatment. Currently, it is unclear which patients are likely to benefit most from this focal salvage treatment. In chapter 8, the development and internal validation of two prediction models for biochemical failure after FS-HDR-BT treatment, in patients with locally radiorecurrent prostate cancer, is described. These models can be used to counsel patients before and during treatment. For easy use in clinical practice, two interactive nomograms were established. Since FS-HDR-BT is an invasive treatment – patients need to undergo spinal anaesthesia and hollow needles are inserted into the prostate – not all patients are eligible for treatment. MR-Linac systems could open up possibilities for a comparable (i.e. single fraction focal treatment with a high dose), non-invasive treatment using high-precision SBRT. In chapter 9, the planning feasibility of single fraction (19.0 Gy) SBRT treatment for locally recurrent prostate cancer on a 1.5 T MR-Linac is investigated. Chapter 10 provides a summary of the presented work. Chapter 11 presents a general discussion of MRI-guided (stereotactic) radiotherapy for the treatment of localised primary and recurrent prostate cancer and describes the future perspectives. 1
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