MRI based prognostic biomarkers for treatment success of Minimal invasive treatment for Uterine Fibroids with Magnetic Resonance guided High Intensity Focused Ultrasound (MR-HIFU)

Research to the optimal criteria for patient selection for treatment of uterine
fibroids with MR-HIFU is worldwide still in progress. In addition to patient
selection, clinical and technical tactics are being investigated to increase
treatment success. Currently, time is often the limiting factor during MR-HIFU
treatment. Therefore, research should focus on making MR-HIFU more time
efficient and how to improve treatment outcomes. The results of MR-HIFU
treatment still show a large variety in volume- and symptom-reduction.
Knowledge of MRI based predictors of success prior to treatment may contribute
to an optimization of patient selection, treatment planning and treatment
outcomes. Secondly, directly after treatment contrast enhanced MRI is needed
for visualizing treatment results. Because HIFU sonications are not allowed
after the administration of a contrast agent, treatment results can only be
visualized after the total treatment. Therefore, MRI parameters (without the
use of a contrast agent) are also studied for capabilities of visualizing
treatment results. Recently published literature suggests that ultrasound
elastography could also predict treatment outcome. Elastography shows a
difference in tissue stiffness of uterine fibroid before treatment, directly
after MR-HIFU and during patients* follow-up. Further research should confirm
these findings.

The aim of this study is to optimize patient selection, to improve treatment
efficacy and to better visualize treatment outcome. The objectives of this
study will be investigated using the same patient population. For the main
endpoints we identified the following MRI parameters: ADC values, quantitative
T2 value and ktrans values, in a prior study (MaSS1). These MRI parameters
possibly could be a useful tool for patient selection prior to treatment
because of their predictive value of treatment outcomes. To improve treatment
efficacy, we want to assess if drug administration of carbetocin during MR-HIFU
therapy. By modifying the treatment protocol, we try to shorten treatment time
and enlarge the ablation volumes. A different purpose of this study is to find
a parameter capable of visualizing and measuring the treated tissue as a
replacement of contrast-enhanced imaging in order to eliminate the use of a
contrast agent. Therefore, we will study the same MRI parameters as mentioned
above and additionally we will introduce a new imaging modality: ultrasound
elastography. This could become a valuable and inexpensive instrument to
evaluate treatment outcome by measuring tissue stiffness. Secondly, it could
make clinical follow-up easier, faster and more cost-effective than an MRI.

The proposed research will concern a single-center study, performed in the
departments of Gynecology and Radiology of the Isala hospital. Patients
undergoing MR-HIFU treatment within this proposed study will be subdivided into
two equal groups. Carbetocin will be administered during the first consecutive
25 treatments (group 1). The control group, last 25 treatments, will receive no
additional medication during MR-HIFU treatment compared to standard care.
Furthermore, all patients will undergo three extra MRI sequences three times
and four times a prolonged ultrasound to perform the elastography measurements.
Additionally, they will be asked to complete UFS-QoL questionnaire four times
as well as a patient satisfaction survey.

Patients included in this study will undergo three extra MRI sequences during
MRI examination. Compared to standard care, this will make the duration of the
MRI twenty minutes longer. The MRI sequences are acquired in a supine position,
just as the conventional sequences during MR-HIFU treatment.
Since patients already receive intravenous medication for pain relief and
conscious sedation, no additional interventions are necessary to administer
carbetocin during MR-HIFU treatment.
At four time points, when patients have their visit at the gynecologists office
(standard care) or when they are hospitalized at the gynecology department (day
of the treatment), patients will undergo one extra measurement during the
vaginal ultrasound at those visits, the elastography. Compared to standard
care, using this elastography function will make the vaginal ultrasound one
minute longer each time. Patients will be already at the hospital at those
time point, so there is no extra visit necessary.
Also the patients are asked to fulfill the UFS-QoL questionnaire four times. To
minimize the burden, patients receive this questionnaire automatically and
based on patients* preference they may reply online or return the form during
their hospital visits.
The additional MRI sequences and prolonged ultrasounds have no additional risks
compared to the standard MRI protocol or standard ultrasound. No additional
contrast agent is used compared too standard MR-HIFU protocol. Since carbetocin
is widely used during other interventions we expect no adverse events during
the administration of this drug and if they do occur, they will be reported to
METC and / or CCMO according to the rules.