Milea Timbergen

195 Follow-up and recurrence The median follow-up time was 49 months (IQR: 21-94 months). Of 329 patients, 83 patients (25.2%) experienced a recurrence. Of these 83 patients, the median time to recurrence was 16 months (IQR: 10-31 months) and the mean time to recurrence was 26 months (SD: 30 months). Table 2 summarizes the number and corresponding frequencies of local tumour recurrence according to the CTNNB1 mutation type. Table 2. Cross-tabulation of recurrence and CTNNB1 mutation type CTNNB1 mutation n S45F T41A S45P WT No recurrence 246 (74.8%) 38 (58%) 115 (75%) 20 (83%) 73 (86%) Recurrence 83 (25.2%) 28 (42%) 39 (25%) 4 (17%) 12 (14%) Total 329 66 154 24 85 WT, wild-type Survival There was a statistically significant (p = 0.019) violation of the proportional hazards assumption for the variable cohort in the multivariable Cox regression, suggesting that baseline hazards differed between studies. Therefore cohort was used as a stratification variable in the Kaplan- Meier analysis and in the univariable and multivariable Cox regression models. Supplemental Figure 1 shows the Kaplan-Meier survival curves with cohort as a stratification variable. Univariable Cox regression models In the univariable Cox regression models, CTNNB1 mutation type, tumour site, and tumour size (log-transformed) were significant prognostic factors for local tumour recurrence after surgical treatment (Table 3). Multivariable Cox regression models In the first multivariable analysis, resection margin status was left out to reduce model complexity. Since none of the included cohorts indicated tumour size as a prognostic factor, the first multivariable model was only adjusted for sex, age, tumour site, and CTNNB1 mutation, stratified by cohort. In this multivariable analysis, the S45P mutation and WT DTF were significantly less likely to recur compared to S45F mutated DTF with a hazard ratio (HR) of 0.32 (95% CI: 0.11-0.97), p = 0.043 and a HR of 0.34 (95% CI: 0.17-0.69), p = 0.003, respectively. A tumour located in the extremities was shown to be an adverse prognostic factor with a HR of 4.09 (95% CI: 2.11-7.92), p < 0.001 compared to trunk/back. The results are displayed in Table 4. 7