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Although the incidence of prostate cancer is high, improvements in treatments have led to high survival rates in patients with low- and intermediate-risk prostate cancer. Therefore, it is even more important that treatments for these patients are minimally invasive and cause as little side effects as possible. The last decades, radiotherapy treatments have changed significantly. One of the clinically introduced innovations is the MR-Linac, a combination of a linear accelerator and an MRI scanner. This machine allows high-quality imaging before and during treatment and daily treatment plan optimisation based on the changing anatomy. This enables more precise radiotherapy and therefore better sparing of healthy organs, which will potentially lead to less side effects such as urinary complaints and erectile dysfunction. This thesis provides insight into the clinical introduction and first period of prostate cancer treatment on the MR-Linac. In part 1 of this thesis, new workflows and technological developments for MRI-guided prostate cancer treatment are presented, which are aimed at enabling extremely hypofractionated radiotherapy for prostate cancer in one or two treatment fractions. With these new workflows, the irradiated volumes can be reduced significantly. Furthermore, early (patient-reported) outcomes of MRI-guided prostate cancer radiotherapy are investigated within two cohort studies, including the international MOMENTUM study. These clinical results are already promising. Part 2 of this thesis focusses on re-irradiation in patients with recurrent prostate cancer after primary radiotherapy treatment. We present research on the feasibility of so-called single-fraction ‘focal salvage’ radiotherapy using external beam radiotherapy on the MR-Linac. The work presented in this thesis is part of the first steps towards MRI-guided, extremely high-precision radiotherapy treatment for (recurrent) prostate cancer in only one or two treatment sessions.

With the clinical introduction of linear accelerators combined with magnetic resonance imaging, such as the 1.5T MR-Linac, new opportunities to further improve radiotherapy treatments arrived. The fact that fast 3D imaging of the patient can be acquired during treatment, allows to explore opportunities to track tumor and organ at risk motion during treatment. Nowadays, the use of hypofractionated radiotherapy treatments for prostate cancer has become more common. To proceed with such ultra-hypofractionated schemes, intrafraction motion monitoring is required. The results described in this thesis study showed that it is possible to determine prostate intrafraction motion using 3D cine-MR imaging using implanted fiducial markers and these results were used as input for ground-truth validation in the development of a soft-tissue based tracking algorithm. Analysis and comparison of the soft-tissue results compared to the previously obtained fiducial marker based results showed that the soft-tissue based method outperforms the fiducial marker based method in terms of robustness and rotation accuracy. Using the soft-tissue based tracking method, the intrafraction motion of the first five prostate cancer patients treated on the 1.5T MR-Linac was then determined. Using this study, we showed that high quality 3D cine-MR imaging and prostate tracking during MR-guided radiotherapy is feasible with beam-on. The obtained intrafraction motion was then used to determine the impact of the prostate intrafraction motion on the delivered dose distribution for the first five prostate cancer patients treated on the 1.5T MR-Linac. The pipeline presented in this thesis demonstrated the first MR-Linac dose reconstruction results based on prostate intrafraction tracking using 3D cine-MR imaging and treatment log files. When considering hypofractionated treatment for high-risk prostate cancer patients, intrafraction motion of the seminal vesicles must be taken into account. To our knowledge, this is the first study to investigate six dimensions of freedom seminal vesicle intrafraction motion from 3D cine-MR during actual MR-guided treatments. Results showed that especially seminal vesicle intrafraction rotation motion is significantly larger than found for the prostate. Moreover, this thesis described a study which investigated the efficacy of always applying a subsequent adapt to position (ATP) procedure to counter the prostate intrafraction motion that occurred during the adapt to shape (ATS) procedure for prostate cancer patients treated on the 1.5T MR-Linac. It was found that due to the continuous and stochastical nature of prostate intrafraction motion, margin reduction below 4 mm require fast intrafraction plan adaptation methods. The work described in this thesis contains analyses determining the influence of intrafraction motion on the dose distribution for patients, coverage probability analyses for the prostate and seminal vesicles and investigated the efficacy of using ATP procedures to reduce the effect of intrafraction motion. In essence, this thesis describes methods to determine intrafraction motion and its influence thereof in the setting of MR-guided radiotherapy for prostate cancer patients. The gained knowledge may be used to reduce radiotherapy margins for hypofractionated prostate radiotherapy and the described methods may be used as input for the introduction of fast plan adaptation methods for MR-guided radiotherapy on the 1.5T MR-Linac.