Data from Lack of Prognostic Value of <i>CTNNB<sub>1</sub></i> Mutation Profile in Desmoid-Type Fibromatosis

<div>AbstractPurpose:<p>This prospective nationwide cohort study aimed to investigate desmoid-type fibromatosis (DF) outcomes, focusing on the prognostic value of <i>CTNNB<sub>1</sub></i> mutations.</p>Experimental Design:<p>ALTITUDES (NCT02867033) was a nationwide prospective cohort study of DF diagnosed between January 2016 and December 2020. At diagnosis, <i>CTNNB<sub>1</sub></i> 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.</p>Results:<p>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 <i>CTNNB<sub>1</sub></i> 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. <i>CTNNB<sub>1</sub></i> 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 (<i>P</i> = 0.03), non-abdominal wall sites (<i>P</i> = 0.05), pain (<i>P</i> = 0.007), and large tumor size (<i>P</i> = 0.025). <i>CTNNB<sub>1</sub></i> p.S45F mutation was not significantly associated with EFS, either in univariate (HR, 1.06; 95% CI, 0.65–1.73; <i>P</i> = 0.81) or in multivariate analysis (HR, 0.91; 95% CI, 0.55–1.49; <i>P</i> = 0.71).</p>Conclusions:<p>We found that CTNNB<sub>1</sub> mutation profile was associated with unfavorable prognostic factors but was not a prognostic factor for EFS.</p><p><i><a href="https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-22-0620" target="_blank">See related commentary by Greene and Van Tine, p. 3911</a></i></p></div>