Clinical implementation of MR-guided adaptive radiotherapy for urological tumors
Authors:   , Tetar Shyama Urmila 
Published: March 2024

Magnetic resonance imaging-guided radiation therapy (MRIgRT) has become a recent major clinical advancement in radiation oncology and MR-Linacs are rapidly implemented in several centers worldwide. MRIgRT provides improved soft-tissue contrast with better visualization of the tumor and surrounding organs at risk compared to current standard cone beam computed tomography and subsequently improves tumor definition and patient set-up. Furthermore, it enables daily online plan adaptation to account for interfraction variability and facilitates gated treatment delivery to account for intrafraction motion. In 2016, MRIgRT was clinically introduced in the Amsterdam University Medical Centers, location VUmc and who became the first Dutch adopters, focusing on treating patients using stereotactic ablative radiotherapy (SABR) with routine daily online plan adaptation for several tumor sites. The work performed in this thesis focuses on the clinical implementation and urological tumors.
The clinical implementation of daily adaptive MRIgRT, including rescanning, recontouring, re-optimizing and plan quality assurance (QA) before every fraction, requiring the presence of a radiation oncologist and a physicist at the treatment console, leading to logistical challenges and adjustments in the radiation delivery workflow for all disciplines. Patients have to stay within the MR-bore for a prolonged period of time and were questioned about their tolerance, which was well tolerated, and about their experience with the video-assisted feedback system for their pro-active contribution in breath-hold gated delivery, which was appreciated and feasible.
MRI has a superior soft tissue contrast and improves visualization of the prostate, the seminal vesicles and surrounding organs at risk like bladder and rectum allowing a precise soft tissue setup. Daily plan adaptation can be used for interfraction changes in anatomy, that may be present because of various bladder and rectum filling and prostate swelling due to radiotherapy. Continuous monitoring during treatment delivery allows for 2D-shift corrections of prostate drifts during the fraction. These benefits of MRIgRT allow the use of smaller safety margins. The results of the first prospective phase II study of stereotactic adaptive MRIgRT for localized prostate cancer are reported of 101 patients. Within the first three months, the maximum cumulative grade ≥ 2 genitourinary toxicity was 23.8%. Grade ≥ 2 gastrointestinal toxicity was seen in 5.0%. Overall, we observed low incidences of early toxicity. No patients reported any relevant impact on daily activities due to urinary symptoms and only 2.2% of patients reported a relevant impact on daily activities due to bowel problems at 1 year. The use of MRIgRT and additional small safety margins, may account for the low rates of toxicity at 1 year follow-up. In our study we evaluated the necessity for adaptation by comparing the dose coverage of the prostate and seminal vesicles of the adapted plans with non-adapted plans using 3 mm and 5 mm safety margin. Daily plan adaptation is time and labor intensive, but, when applying smaller margins of 3 mm, daily plan adaptation is necessary to obtain adequate dose coverage of the seminal vesicles.
MRIgRT is a promising option to deliver renal SABR, because it enables adequate respiratory motion management for breath-hold gated treatment delivery to spare remaining kidney function. Precise delivery of high radiation dose can be challenging with close proximity of critical adjacent organs such as small bowel, duodenum and stomach, while the kidney is moving in free-breathing respiratory motion. Our evaluation of 36 patients showed good local control of 95.2% at 1 year and minimal side-effects with no reported grade ≥ 3 toxicity.
In summary, the work performed for this thesis describes the first clinical experience with MRIgRT for prostate cancer and renal cell cancer and opens the door for further improvements of MRIgRT for urological tumors.