Lack of prognostic value of CTNNB1 mutation profile in desmoid-type fibromatosis

Summary

Purpose: This prospective nationwide cohort study aimed to investigate desmoid-type fibromatosis (DF) outcomes, focusing on the prognostic value of CTNNB1 mutations. Experimental design: ALTITUDES (NCT02867033) was a nationwide prospective cohort study of DF diagnosed between January 2016 and December 2020. At diagnosis, CTNNB1 molecular alterations were identified using next-generation sequencing or Sanger sequencing. The primary endpoint was event-free survival (EFS) (progression, relapse, or death). We enrolled 628 patients managed by active surveillance (AS), surgical resection (SR), or systemic treatment as front-line therapy. Results: Overall, 516 (82.2%) patients (368 females [71.3%], median age 40.3 years [range, 1-89]) were eligible for analysis. In 435 (84.3%) cases, there was one CTNNB1 molecular alteration: p.T41A, p.S45F, or p.S45P. The front-line management was AS in 352 (68.2%), SR in 120 (23.3%), and systemic treatments in 44 (8.5%) patients. CTNNB1 mutation distribution was similar across the three therapeutic groups. The median follow-up period was 24.7 (range, 0.4-59.7) months. The estimated 3-year EFS rate was 66.2% (95%CI, 60.5%-71.2%). DF harboring p.S45F was significantly associated with male sex (p=0.03), non-abdominal wall sites (p=0.05), pain (p=0.007), and large tumor size (p=0.025). CTNNB1 p.S45F mutation was not significantly associated with EFS, either in univariate (hazard ratio [HR]=1.06; 95% confidence interval [CI], 0.65-1.73; p=0.81), or in multivariate analysis (HR=0.91; 95% CI, 0.55-1.49; p=0.71). Conclusions: We found that CTNNB1 mutation profile was associated with unfavorable prognostic factors but was not a prognostic factor for EFS.