ADAPTIVE MR-GUIDED RADIOTHERAPY: FROM CONCEPT TO ROUTINE PRACTICE

Radiotherapy is an established curative treatment for cancer and is also widely used in the treatment of metastatic disease. Magnetic resonance guided radiotherapy (MRgRT) represents a major treatment advance as it permits precise soft tissue setup and the continuous visualization of tumors and surrounding organs, thereby improving the safety and effectiveness of radiotherapy delivery. MRgRT was first introduced clinically in 2014, and in 2016, the Amsterdam UMC became the first Dutch adopters, focusing on treating patients using stereotactic ablative radiotherapy (SABR). The work performed in this thesis describes a number of approaches developed in order to ensure a practical and feasible workflow for MRgRT delivery of SABR using daily on-couch adaptive treatment plan delivery whenever possible. A key development was the strategy for plan adaptation using only a single treatment optimization step that only requires clinicians to review and adjust organ contours located within 2-3 cm from the target. This novel and fast approach resulted in treatment plans meeting all clinical constraints, and contributed to the feasibility of using daily adaptive MRgRT, as plan adaptation added only about 15 minutes to the total workflow. Use of this strategy has led to more than 1200 patients undergoing 6000 treatment fractions to tumor in the prostate, pancreas, high-risk lung cancer, renal- and adrenal lesions, and liver metastases. Almost all fractions have been delivered using the adapted plan. The delivery of daily adapted MRgRT requires time slots of approximately 45 to 60 minutes for SABR delivery. To reduce treatment times further, it is essential to identify patients groups that are less likely to benefit from having a new daily radiotherapy plan, and our studies identified patients with abdominal tumors who could be treated faster without plan adaptation. This will permit a more efficient use of resources. Organs in the body can move during treatment, leading to a need for intrafractional adapted radiotherapy plans. To approach this problem, we used fraction partitioning with successive re-optimization, and showed that plan adaptation benefits both tumor coverage and healthy organ sparing. Similarly, plan adaptation during treatment was also shown to be useful in some instances, although it can prolong the treatment duration to 90 minutes. The continuous visualization of anatomical changes during MRgRT allows for a more accurate reconstruction of delivered doses to tumors and organs. Our study of accumulated radiation doses revealed that the accumulated bladder dose in 100 patients with prostate cancer better predicted acute radiation-related urinary toxicity, than was possible using the baseline radiotherapy plans. This finding opens the door for personalized radiation delivery approaches using prospective dose accumulation for each subsequent fraction. In summary, the work performed for this thesis has allowed for fast and accurate delivery of MRgRT, and it has identified a number of areas for further improvements in treatment efficiency