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The Desmoid Tumor Research Foundation

September 2022

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

Author Information

Penel N(1), Bonvalot S (2), Bimbai A (3), Meurgey A (4), Le Loarer F (5), Salas S (6), Piperno-Neumann S (2), Chevreau C (7), Boudou-Rouquette P (8), Dubray-Longeras P (9), Kurtz J (10), Guillemet C (11), Bompas E (12), Italiano A (5), Le Cesne A (13), Orbach D (14), Thery J (3), Le Deley M (1), Blay J (15), Mir O (16).

(1) Centre Oscar Lambret, Lille, France. (2) Institute Curie, Paris, France. (3) Centre Oscar Lambret, France.(4) Centre Léon Bérard, France. (5) Institut Bergonié, (6) Aix-Marseille University, MARSEILLE, France. (7) University Institute of Cancerology, Toulouse, France. (8) Cochin Hospital, AP-HP, Paris Descartes University, PARIS, France. (9) Centre Jean Perrin, France. (10) ICANS, France. (11) Centre Henri Becquerel, France. (12) Centre René Gaducheau, Saint Herblain, France. (13) Gustave Roussy Cancer Campus, Villejuif, France. (14) Institute Curie, Paris, France, France. (15) Centre Leon Bérard, Univ Claude Bernard, Unicancer, Lyon, France. (16) Gustave Roussy Cancer Institute, Villejuif, France.Bordeaux, France.

Publication

Clin Cancer Res

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.

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