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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.

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.