Milea Timbergen

187 Introduction Desmoid-type fibromatosis (DTF) was first described 185 years ago by MacFarlane, and it was named desmoid in 1838 by Müller who referred to the Greek word “desmos”, meaning “a tendon like structure” 1, 2 . Ever since, the understanding of this non- metastasizing and histologically benign tumour has grown remarkably 3 . Its potential to arise in musculoaponeurotic structures at virtually any body site and to invade surrounding structures poses therapeutic challenges. A histological biopsy, with nuclear ß-catenin staining, can confirm the diagnosis 4 . In recent years, there has been a tendency for an active surveillance approach in asymptomatic patients and several prospective clinical trials (NCT02547831, Italy, NTR 4714, the Netherlands, and NCT01801176, France) are conducted to evaluate the safety of this approach 5-9 . For progressive patients, surgical resection, isolated limb perfusion, radiotherapy and systemic therapy are available treatment options 10 . The variable growth behaviour with the possibility of tumour progression, growth arrest, or regression without treatment, makes this tumour unpredictable 5, 11, 12 . Local recurrence after surgery, especially in case of tumours located in the extremities, the head/neck region and intra-abdominal, occur frequently 13, 14 . The genetic roots of DTF have been extensively studied 15 . Desmoid tumours can occur as part of the inherited condition Familial Adenomatous Polyposis (FAP) and the FAP subtype; Gardner’s syndrome 16 . Both conditions are associated with mutations found in the adenomatous polyposis coli gene on chromosome 5, and are known for the development of hundreds of pre-malignant colonic polyps. The development of mainly intra-abdominal DTF tumours is one of the associated manifestations, with a cumulative lifetime risk reaching 21% 17, 18 . Both syndromes will not be further discussed in this meta-analysis since the origin and clinical course of these diseases and the DTF tumours for which they predispose, differ from the sporadic variant of DTF. The sporadic variant is associated with extra-abdominal or abdominal wall desmoid tumours and finds its origin in the CTNNB1 (ß-catenin) gene 15, 19-22 . β-catenin is involved in several downstream signaling pathways, functions as a transcriptional activator and is involved in cell-cell adhesion 19 . The mutations are located on exon 3, causing mostly the following amino acid changes: T41A, S45F and S45P 19, 23 . The remainder of tumours, less than 5%, that lack a mutation in the CTNNB1 gene, and of which the underlying genetic aberrations are not entirely clear yet, are called wild-types (WT) 15 . The use of the CTNNB1 mutation as a prognostic factor for recurrence after resection has been the subject of several studies. Some studies report that S45F-mutated DTF tumours exhibit a higher recurrence rate after primary resection than WT or other CTNNB1- mutated 7