Milea Timbergen

23 Introduction Desmoid-type fibromatosis (DTF) is a clonal fibroblastic proliferation of the soft tissues that arises in musculoaponeurotic structures 1 . It has a mesenchymal origin since DTF tumours express cell surface markers and genes that are characteristic of mesenchymal stem cells 2 . The incidence in the Dutch population is 5 patients per million people per year 3 . Unfortunately, worldwide epidemiological data is lacking. The abdominal wall and the trunk are the most common localisations and symptoms can vary, depending on tumour location and size 4, 5 . Roughly, two types can be distinguished: sporadic and hereditary DTF. The first type is considered to be a monoclonal disorder, since it derives from a single progenitor cell 6 . This “sporadic” type is commonly localized extra-abdominally or in the abdominal wall 5 . The precise aetiology of sporadic DTF remains tenuous. Several studies report correlations with (spontaneous or iatrogenic) trauma and hormonal status 7-10 . The hereditary type occurs more frequent in patients with familial adenomatous polyposis (FAP), and causes intra-abdominal DTF tumours. This DTF type is an autosomal dominant disorder caused by germline mutation of the adenomatous polyposis coli ( APC ) gene, and is associated with the formation of hundreds of colon polyps which can transform into malignant colorectal tumours in time (reviewed by De Marchis et al. 11 and Lips et al. 12 ). The cumulative rate of DTF in FAP patients is 20.6% at 60 years of age 13 . Desmoid-type fibromatosis is considered to be a borderline tumour because of its incapability to metastasize 1 . The mortality of this disease is low and seldom described in literature. However, local aggressive growth can cause significant morbidity by infiltrating surrounding structures, causing pain or functional loss. Currently, “wait and see” is the first line therapy in case of asymptomatic DTF. Several retrospective studies report that a minority of patients on a “wait and see” protocol experience progression and that progression usually occurs within two years after tumour development 14 . Additionally, up to one third of patients experience disease regression without any form of treatment 15-17 . Three prospective studies investigating a “wait and see” approach (NCT02547831, Italy; NTR 4714, the Netherlands; NCT01801176, France) examine the natural growth behaviour of DTF and their relationship with CTNNB1 mutations 18-20 . Surgery is the treatment of choice in case of failure of the “wait and see” management 21 . Radiotherapy is mainly used as an adjuvant treatment in case of incomplete surgical resection. Radiotherapy as a single treatment modality may be considered for patients in whom local control is the primary treatment goal 21 . When both surgery and radiotherapy are not an option due to tumour localization (e.g., near vital structures), or because of comorbidities, several other treatment options are available like local cryoablation and partial systemic chemotherapy via 2