title: Correlation of CTNNB1 Mutation Status with Progression Arrest Rate in RECIST Progressive Desmoid-Type Fibromatosis Treated with Imatinib: Translational Research Results from a Phase 2 Study of the German Interdisciplinary Sarcoma Group (GISG-01).
abstract: CTNNB1 gene mutations are the molecular key events in the majority of sporadic desmoid-type fibromatosis (DF). The specific S45F mutation has been reported to be associated with a more aggressive clinical course in DF. For the current study, the CTNNB1 mutation status was analyzed in DF samples from the prospective German Interdisciplinary Sarcoma Group (GISG) phase 2 study evaluating imatinib to induce progression arrest in DF Response Evaluation Criteria In Solid Tumors (RECIST) progressive patients.
  
  
  
  Thirty-seven patients were treated with a planned dose of imatinib 800 mg daily over 2 years (NCT01137916). The progression arrest rate (PAR) after 6 months of treatment was the primary endpoint of the study. CTNNB1 exon 3 mutation status was analyzed using Sanger sequencing.
  
  
  
  Thirty-three (97 %) of 34 patients reaching the primary endpoint were evaluable for CTNNB1 mutation exon 3 status. T41A mutations accounted for 30.3 % of the study samples and S45 mutations for 48.5 %, whereas CTNNB1 wild-type status was found in 21.2 %. The respective PAR at 6 months was 70, 81, and 43 %. Patients harboring CTNNB1 mutations demonstrated a higher PAR compared to wild-type DF. There was a statistically significant difference comparing patients with S45F mutations (85 % PAR) versus wild-type status (p = 0.05).
  
  
  
  Mutations at position S45 were overrepresented in the GISG-01 trial recruiting RECIST progressive patients only. The positive correlation of CTNNB1 mutation status with the progression arrest rate after imatinib therapy supports the idea of a potential predictive impact of the mutation status on DF treatment decision making.
authors: Sarcoma Unit, Interdisciplinary Tumor Center, Mannheim University Medical Center, University of Heidelberg, Mannheim, Germany. bernd.kasper@umm.de.
authors: Bernd
authors: B
authors: Kasper
authors: Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors: Viktor
authors: V
authors: Gruenwald
authors: Sarcoma Center Berlin-Brandenburg, HELIOS Klinikum Berlin-Buch, Berlin, Germany.
authors: Peter
authors: P
authors: Reichardt
authors: Sarcoma Center, West German Cancer Center, Essen, Germany.
authors: Sebastian
authors: S
authors: Bauer
authors: Sarcoma Unit, Interdisciplinary Tumor Center, Mannheim University Medical Center, University of Heidelberg, Mannheim, Germany.
authors: Peter
authors: P
authors: Hohenberger
authors: Institute of Pathology, Friedrich Alexander University, Erlangen-Nürnberg, Erlangen, Germany.
authors: Florian
authors: F
authors: Haller
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D018450:Disease Progression; D018222:Desmoid Tumors / Q000188:drug therapy / Q000235:genetics*; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D009154:Mutation; D011379:Prognosis; D011446:Prospective Studies; D066066:Response Evaluation Criteria in Solid Tumors; D015996:Survival Rate; D057170:Translational Research, Biomedical; D051176:beta Catenin / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D051176:beta Catenin; D000068877:Imatinib Mesylate