Magnetic Resonance imaging-guided high intensity focused ultrasound for patients with Desmoid-type fibromatosis

Rationale: Desmoid-type fibromatosis (DTF) is a rare, histologically benign soft tissue tumor. Although incapable of metastasizing, the clinical course is unpredictable and can be aggressive because of local invasive growth. Many intensive treatments (i.e. surgery, systemic treatments, radiotherapy) may be considered in patients with symptomatic disease but unfortunately, these ‘traditional’ treatment options do not guarantee success. Local recurrence after surgery remains high and the response rates after systemic treatment and radiotherapy are disappointing. Active surveillance is now recommended as a first line management for most patients with DTF. However, symptoms can be severe, and patients are often limited in their daily life because of pain, functional deficits, and/or psychological problems. Therefore, development of new treatment modalities which improve quality of life and/or achieve tumor control, while minimizing any possible harm, are warranted. MR-HIFU is a promising non-invasive technique that uses focused ultrasound waves to thermally ablate tumors, while minimizing side effects to surrounding healthy tissues. Given the promising outcomes of previous studies of MR-HIFU as treatment modality for DTF patients, we hypothesize that DTF patients could benefit from treatment with MR-HIFU.

Objective: The aim of this study is to assess the efficacy of MR-HIFU as a treatment modality for desmoid-type fibromatosis (DTF).

Study design: This is a two-stage, open-label, single-arm, phase 2 prospective study.

Study population: All adult patients with DTF with failure of active surveillance (due to tumor growth and/or new or worsening symptoms ) for their current desmoid tumor are considered eligible for the study.

Intervention (if applicable): All patients will undergo an adequate MR-HIFU treatment procedure with the aim of total tumor ablation (consisting of a single or multiple treatments).

Main study parameters/endpoints: Primary outcome of the trial will be the patient satisfaction rate 12 months after the completion of the MR-HIFU procedure(s). Patient satisfaction is being defined as the number of patients achieving their own personal satisfaction score. Secondary outcomes include the presence of non-perfused volume on MRI after the MR-HIFU procedure, change in tumor volume, the response rate according to the Response Evaluation Criteria in Solid Tumors version 1.1. (RECIST v.1.1) and mRECIST criteria, the number of patients who need a re-intervention, time to (re)growth, duration of tumor response, and patient satisfaction, adverse events, change in symptoms, pain scores, and health-related quality of life (HRQoL) in the first 12 months after treatment.

Patients with desmoid-type fibromatosis could benefit from treatment with MR-HIFU.

An interim analysis will be done after the first 8 patients have been in follow-up for 12 months after completion of MR-HIFU treatment (phase 1). If response is observed in >1 patients, another 5 patients will be included and treated with MR-HIFU (phase 2).

With regard to the timepoints of the primary and secondary outcomes, we refer to the section 'primary and secondary outcomes'.

MR-HIFU treatment