Lack of Prognostic Value of <i>CTNNB1</i> Mutation Profile in Desmoid-Type Fibromatosis
Nicolas Penel, Sylvie Bonvalot, André-Michel Bimbai, Alexandra Meurgey, François Le Loarer, Sébastien Salas, Sophie Piperno‐Neumann, Christine Chevreau, Pascaline Boudou‐Rouquette, Pascale Dubray‐Longeras, Jean‐Emmanuel Kurtz, Cécile Guillemet, Emmanuelle Bompas, Antoîne Italiano, Axel Le Cesne, Daniel Orbach, Julien Thery, Marie‐Cécile Le Deley, Jean‐Yves Blay, Olivier Mir
Abstract
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, surgical resection, or systemic treatment as first-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 first-line management was active surveillance in 352 (68.2%), surgical resection 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% confidence interval (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 (HR, 1.06; 95% 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. See related commentary by Greene and Van Tine, p. 3911.