MR-guided radiotherapy for patients with lymph node oligometastases

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.