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Magnetic resonance imaging (MRI) provides superior soft tissue contrast compared with computed tomography (CT) imaging. Image guidance during radiotherapy treatments is of pivotal importance to ensure accurate deposition of the radiation dose at the clinical target. Therefore, most radiotherapy treatment facilities offer fast imaging before each treatment session, but often this relies on cone beam CT (CBCT) imaging. The MR-linac is a treatment facility that combines an MRI scanner and a linear accelerator (linac), and it allows diagnostic-quality soft tissue contrast to guide each radiotherapy delivery. In this thesis, the application of stereotactic body radiotherapy (SBRT) for patients with very limited metastatic disease (oligometastases) in lymph nodes is investigated, with a focus on delivery using the 1.5 T MR-linac. Feasibility of multi-fraction SBRT delivery using the 1.5 T MR-linac has been shown for five patients with lymph node oligometastases. This was the first clinical application of 1.5 T MR-linac after acquisition of the Conformité Européenne (CE)-certification. In this feasibility study new treatment plans were generated for each treatment session based on the daily anatomy, all treatment sessions were completed within 60 minutes and all quality assurance tests were passed, including independent 3D dose calculations and film measurements. Dosimetric evaluations of the MR-linac treatments compose a large part of this thesis. Different methods for daily online plan optimization were compared, treatment margins were evaluated, the need for patient immobilization using a vacuum cushion was investigated and the online adaptive MR-guided treatments were benchmarked against conventional treatments on CBCT-linac. From these dosimetric evaluations, it was concluded that extensive daily re-planning with manual contour adaptation is needed to gain profit from treatment on an MR-linac compared with a CBCT-linac, such as for patients with multiple target volumes or for patients with a critical healthy organ nearby for which adherence to a dose limit was challenging. However, the longer duration of treatment sessions on an MR-linac seems to impact the dosimetric benefit of daily MR-guided plan adaptation. Repeated plan adaptation during the treatment sessions and faster workflows including (improved) automatic segmentation and faster plan optimization are expected to increase the benefit from MR-linac treatments in the future. The second part of this thesis has been focused on the clinical outcomes after SBRT for lymph node oligometastases. Most patients were treated for prostate cancer lymph node oligometastases, which had been diagnosed using prostate-specific membrane antigen (PSMA)-PET scans. For these patients, the median progression-free survival (PFS), defined as time to occurrence of a new metastatic lesion or biochemical progression, was found to be 16 months at a median follow-up of 21 months. Baseline patient characteristics were investigated as potential predictors of shorter PFS and a preliminary risk score for PFS was created. Because of the relatively short PFS, most patients might benefit from combined treatments consisting of SBRT and some form of systemic therapy. Finally, SBRT was confirmed to be a safe treatment for lymph node oligometastases, with limited toxicity and a mild and transient impact on quality of life, mainly fatigue.

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.

Radiotherapy treatments need adequate quality control (QC) to ensure a correct delivery of the prescribed dose to the target area. One of the most extended safety nets for treatments in conventional radiotherapy machines is in-vivo EPID dosimetry, which uses the dose acquired by an Electronic Portal Imaging Device (EPID) during treatment to accurately reconstruct the dose as it was delivered to the patient.We developed a method to validate radiotherapy treatments delivered on a novel system: the Unity MR-Linac. This machine, which combines a radiation source (linac) and an imaging device (MRI), will help to irradiate tumors more accurately by means of a new range of techniques only available thanks to the image guidance of the MRI during irradiation. The verification of such treatments can be performed by using images of the delivered beam captured by an EPID situated opposite to the radiation source, behind the cryostat of the MRI scanner. This project focuses on the adaptation of an already existing algorithm used with conventional linacs to the new physics and design characteristics of the Unity MR-linac. The main challenge for this adaptation is the presence of the MRI scanner between the patient and the EPID, acting as a secondary source of scatter and as an attenuation medium for the beam.

The purpose of this thesis is to investigate the inuence of the MR scanner on dosimetry for the radiation modality, and to investigate the possible solutions for the dosimetric measurements discussed in section 1.7. Chapter 2 investigates the feasibility to use a standardized national reference dosimetry protocol for the MR-linac. Firstly, the feasibility of using an ionisation chamber in an MR-linac was assessed by investigating possible inuences of the magnetic field on an NE2571 Farmer type ionisation chamber characteristics: linearity, repeatability, orientation in the magnetic field; and AAPM TG51 correction factor for voltage polarity and ion recombination. Secondly, the inuence of the permanent 1.5 T magnetic field on the NE2571 chamber reading was quantified. Chapter 3 presents the design and performance of a prototype MR-linac compatible scanning water phantom. In order to use a scanning water phantom, the performance of air filled ionisation chambers in the magnetic field must be characterised. The performance of the scanning water phantom will be validated at a clinical set-up in a 0 T magnetic field. Inside the MR-linac set-up, the performance of the MR-linac scanning water phantom is validated using radiographic film. Chapter 4 investigates the performance of the IC PROFILERTM, a multi-axis ionisation chamber array, in a 1.5 T magnetic field. The inuence of the magnetic field on the IC PROFILERTM reproducibility, dose response linearity, pulse rate frequency dependence, power to electronics, panel orientation and ionisation chamber shape are investigated. IC PROFILERTM dose profiles were compared with film dose profiles obtained simultaneously in the MR-linac. Chapter 5 investigates the feasibility of using the STARCHECKTM multi-axis ionisation chamber array panel, in a transverse 1.5 T magnetic field. The method of investigation is similar to that used for the IC PROFILERTM in chapter 4. The investigated characteristics are short term reproducibility, dose response linearity, accuracy of output factor measurements and the inuence of the magnetic field on a purposefully introduced misalignment. As a validation of feasibility, STARCHECKTM measurements were compared with film measurements simultaneously obtained in the MR-linac. Chapter 6 investigates the feasibility of using an MV portal imager in an MRlinac set-up. MV imaging integrated with the MR-linac has the potential to provide an independent position verification tool, a field edge check and a calibration for alignment of the coordinate systems of the MRI and the accelerator. A standard aSi MV detector panel is added to the system and both qualitative and quantitative performance are determined. Chapter 7 examines the performance characteristics of the ArcCHECK-MR QA system in a transverse 1.5 T magnetic field. This ArcCHECK-MR system is used for QA of patient treatment plans. To this end, the short-term reproducibility, dose linearity, dose rate dependence, field size dependence, dose per pulse dependence and inter-diode variation of the ArcCHECK-MR diodes were evaluated on a conventional linac and on the MR-linac. Chapter 8 investigates the inuence of the closed bore MRI scanner structures on several radiation beam characteristics for squared fields of sizes 5.6, 9.8 and 23.8 cm2. The MR-linac set-up will be implemented into a Monte Carlo simulation environment facilitating dose profile simulations in a 1.5 T magnetic field with and without MRI scanner structures. The results of the Monte Carlo simulations will be validated against scanning water phantom measurement results obtained in the MR-linac for the PDD and lateral profiles.

First, we present two offline position verification methods which can be used in radiotherapy for detecting the position of the bony anatomy of a patient automatically with portal imaging, even if every single portal image of each segment of an (IMRT) treatment beam contains insufficient matching information. Additional position verification fields will no longer be necessary, which speeds up the treatment and reduces the total dose to the patient. Second, a tool is described which enhances the way tumors can be delineated by using multiple imaging modalities. This tool is especially useful when multiple MRI sequences are available as well as the standard planning CT. We also developed a marker which is visible on MRI and on EPID. A separate CT for detecting the markers is no longer needed. The gold marker with steel core can be detected on various MRI sequences, reducing the overall systematic radiotherapy treatment error. The MRI linear accelerator (MRL) facilitates continuous patient anatomy updates regarding translations, rotations and deformations of targets and OAR during a course of radiotherapy. Accounting for this information demands high speed, online IMRT re-optimization. Therefore, we developed a fast IMRT optimization system which combines a GPU based Monte-Carlo dose calculation engine for online beamlet generation (GPUMCD) and a fast inverse dose optimization algorithm (FIDO). We show that for the presented cases the beamlets generation and optimization routines are fast enough for online IMRT planning. Furthermore, there is no influence of the magnetic field on plan quality and complexity, and equal optimization constraints at 0T and 1.5T lead to almost identical dose distributions. One of the most significant effects of the transverse magnetic field on the dose distribution occur around air cavities: the electron return effect (ERE). We investigated the effects of non-stationary spherical air cavities on IMRT dose delivery in 0.35T and 1.5T transverse magnetic fields by using Monte Carlo simulations. Our observations show the intrinsic ERE compensation by equidistant and opposing beam configurations for moving spherical air cavities within the target area. IMRT gives some additional compensation, but only in the case of correct positioning of the air cavity according to the IMRT compensation. For air cavities appearing or disappearing during a fraction this correct positioning is absent and gating or plan re-optimization should be used. Finally, we introduce an online 'virtual couch shift' (VCS): we translate and/or rotate the pre-treatment dose distribution to compensate for the changes in patient anatomy and generate a new plan which delivers the transformed dose distribution automatically. The VCS is the first step towards compensating all anatomical changes (translation, rotations, and deformations) by online re-optimization of the IMRT dose distribution.