Towards a minimally invasive approach of atypical lipomatous tumors: the MINIMALIST trial

Rationale: Patients with an atypical lipomatous tumor (ALT) have an excellent prognosis, approaching 100% survival after 10 years of follow-up. Currently, we might be 'overtreating' these patients with surgery and radiotherapy, thereby inducing morbidity and even mortality. Despite this excellent prognosis, active surveillance is barely applied in these patients. Furthermore, survival might not be the only appropriate outcome to measure, and other outcomes, such as health-related quality of life (HRQoL), might have become more relevant. Second, it can be very difficult to distinguish between ALTs and lipomas based on imaging. Therefore, these patients currently need a painful and invasive biopsy for pathological examination to make the distinction. Finally, due to the rarity and heterogeneity of liposarcomas, it is a challenge to collect a large homogeneous set of tissue samples for translational research.

Objective: The aim is to develop a minimally invasive approach of both diagnosing and treating ALTs, saving these patients a biopsy, surgery-related complications and morbidities amongst others. As a first step towards a minimally invasive diagnosis, a radiomics model was developed on a retrospective cohort to distinguish lipomas from ALTs based on MRI scans. In the current study, one of the objectives is to prospectively validate this radiomics model. Second, to prevent the 'overtreatment' of ALT patients, the aim is to explore the feasibility and safety of active surveillance (AS) as a treatment option for ALTs, including evaluating the HRQoL. Lastly, the objective is to build a biobank of the biopsies and, if applicable, resection specimens obtained during the study for future translational research.

Study design: Prospective single center observational cohort study

Study population: Patients with a lipomatous tumor suspected for ALT or lipoma, aged ≥18 years, who did not receive any treatment for their tumor yet.

Intervention (if applicable): All patients will undergo an MRI scan and a biopsy, as part of the routine diagnostic work-up. If proven ALT, patients may choose either surgery (standard care) or AS ('intervention'). Follow-up for patients choosing AS, will be performed according the study protocol, including regular imaging.

Main study parameters/endpoints: The main study endpoints are choice of treatment (i.e. AS or surgery) to determine the feasibility of AS and the occurrence of dedifferentiation to determine the safety of AS. AS will be considered feasible if at least 25% of the patients prefers AS over surgery, of whom at least 50% is still being treated with AS after one year of follow-up. AS will be considered safe if dedifferentiation occurs in <5% of the patients. Dedifferentiation has to be pathologically proven upon biopsy or resection. Second, to validate the accuracy of the radiomics model, the area under the ROC curve (AUC), accuracy, sensitivity, specificity, negative predictive value and positive predictive value will be used. To evaluate the prevalence and changes in HRQoL we will use different HRQoL questionnaires.

Active surveillance is a reasonable treatment option for selected ALT patients

Interim analysis after 1 year follow-up for 50 patients

Active surveillance