Milea Timbergen

12 Therefore, we investigated whether we could potentially explain this difference by studying mRNA expression data of known Wnt target genes in Chapter 3 . DNA methylation is an epigenetic modification that influences gene expression and hence, gene activity 52 . Abnormal DNA methylation have been described in various solid tumours and sarcomas 53, 54 . In Chapter 4 we examined and compared genome-wide DNA methylation patterns of DTF tumours containing a T41A or an S45F CTNNB1 mutation. Part II - Diagnosis and Treatment Radiomics, makes use of computational computer algorithms designed to link imaging features to molecular, pathological and clinical features 55 . By the annotation of tumours on conventional imaging, already obtained during the routine diagnostic work-up, radiomics can be used to contribute to diagnosis, prognosis and treatment decision making 56, 57 . In Chapter 5 we investigated whether radiomics can be used to differentiate extremity DTF from other extremity tumours such as fibromyxosarcomas, myxoid liposarcomas and leiomyosarcomas on pre-treatments MRI. Additionally, we investigated whether our radiomics model could be used to differentiate the various CTNNB1 mutation types. In recent years, active surveillance has obtained a more prominent role in the treatment of asymptomatic DTF. The recommendation that active surveillance should be the front-line approach for treating DTF published in the first European consensus guideline (2015) 58 , was based on the results of five retrospective studies 20, 59-62 . As the results of the three prospective studies 63-65 are still awaited, we performed a systematic literature review described in Chapter 6 . This review systematically evaluates the results of the active surveillance approach in published retrospective series. Since DTF is a rare disease, randomized controlled trials to investigate the efficacy of certain treatments are scarce. For a long time, surgery remained the gold standard for treating DTF; however, the risk of local recurrence after surgery was high, between 20% and 68% 66, 67 . Several studies 12, 49-51 found a significant correlation between risk of recurrence and mutation status and claimed that the S45F mutated DTF tumours have the highest chance of recurrence. Often, these studies included both primary and recurrent DTF tumours, and 1