Milea Timbergen

199 extremities, is an adverse prognostic factor (p < 0.001) for recurrence compared to tumours located on the trunk/back. Females represented the majority of patients in the current cohort (75%). This is in line with previous reports describing nationwide cohorts by Broekhoven et al. 47 (71.3% females) and Penel et al. 36 (72.6% females). In the current study, no statistically significant association between sex and mutation type (p = 0.643) could be found. Additionally univariable analysis did not identify sex as a prognostic marker for recurrence (p = 0.290). The added value and the strength of the current study is the use of individual patient data, which created a relatively large cohort of patients that receive the same treatment for their primary DTF, but there are some limitations to take into account. The use of IPD demanded the formation of new variables, for example, T0 which was defined as date of surgery. Unfortunately, this variable was not available for all patients and was solved by the use of “date of diagnosis” in a small part of patients. Another example of a new variable which had to be created was tumour site. Although a statistically significant result was found in both univariable and multivariable analyses, one should keep in mind that there is a relatively large group of patients having an extra-abdominally located tumour without any further specification (extra-abdominal NS). A major limitation, considering the present knowledge, is the relatively large number of patients with WT tumours in the current cohort. Multiple studies report that CTNNB1 mutations are not always detected by Sanger sequencing due to the low frequency of mutant alleles and the relatively low sensitivity of the technique. This can lead to incorrect allocation to the WT group while having CTNNB1 or other, novel, mutations 15, 48, 49 . The CTNNB1 genotyping protocols, used in the included studies (Supplemental Table 5), focused on the presence of a CTNNB1 mutation in exon 3 and provided no information about the presence of other mutations that may be present in the tumours. Another limitation is the heterogeneity of included studies which differed in primary outcome and differences in follow-up procedures, possibly leading to missing a certain number of recurrent tumours. This is also reflected by the variable recurrence rates reported by the included studies. Moreover, the rarity of DTF is reflected by the limited number of available studies with available CTNNB1 type assessing recurrence, and led to the inclusion of studies with a high risk of bias. As the aim of the current study was to gain insight into the prognostic values of the CTNNB1 mutation, every study, regardless of their sample size, was included in this meta-analysis. Several studies could not be included in this meta-analysis due to potential cohort overlap and due to the impossibility to acquire the 7