Milea Timbergen

186 Abstract Background The majority of sporadic desmoid-type fibromatosis (DTF) tumours harbor a CTNNB1 (ß-catenin) mutation: T41A, S45F and S45P or are wild-type (WT). Results are conflicting regarding the recurrence risk after surgery for these mutation types. This meta-analysis (PROSPERO CRD42018100653) uses individual patient data (IPD) to assess the association between recurrence and CTNNB1 mutation status in surgically treated adult DTF patients. Materials and methods A systematic literature search was performed on June 6th, 2018. IPD from eligible studies was used to analyse differences in recurrence according to CTNNB1 mutation status using Cox proportional hazards analysis. Predictive factors included: sex, age, mutation type, tumour site, tumour size, resection margin status, and cohort. The PRISMA-IPD guideline was used. Results Seven studies, describing retrospective cohorts were included and the IPD of 329 patients were used of whom 154 (46.8%) had a T41A mutation, 66 (20.1%) a S45F mutation, and 24 (7.3%) a S45P mutation, whereas 85 (25.8%) patients had a WT CTNNB1 . Eighty-three patients (25.2%) experienced recurrence. Multivariable analysis, adjusting for sex, age and tumour site yielded a p-value of 0.011 for CTNNB1 mutation. Additional adjustment for tumour size yielded a p-value of 0.082 with hazard ratios (HR) of 0.83 (95% confidence interval [CI]: 0.48-1.42), 0.37 (95% CI: 0.12-1.14) and 0.44 (95% CI: 0.21-0.92) for T41A, S45P and WT DTF tumours compared S45F DTF tumours. The effect modification between tumour size and mutation type suggest that tumour size is an important mediator for recurrence. Conclusions Primary sporadic DTFs harbouring a CTNNB1 S45F mutation have a higher risk of recurrence after surgery compared to T41A, S45P and WT DTF, but this association appears to be mediated by tumour size. 7