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)
Kasper B, Gruenwald V, Reichardt P, Bauer S, Hohenberger P, Haller F (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 23
Pages Range: 1924-7
Journal Issue: 6
DOI: 10.1245/s10434-016-5132-4
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.
Involved external institutions
Ruprecht-Karls-Universität Heidelberg
Germany (DE)
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Germany (DE)
HELIOS Kliniken
Germany (DE)
Universitätsklinikum Essen
Germany (DE)
Germany (DE)
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Germany (DE)
HELIOS Kliniken
Germany (DE)
Universitätsklinikum Essen
Germany (DE)
How to cite
APA:
Kasper, B., Gruenwald, V., Reichardt, P., Bauer, S., Hohenberger, P., & Haller, F. (2016). 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). Annals of Surgical Oncology, 23(6), 1924-7. https://doi.org/10.1245/s10434-016-5132-4
MLA:
Kasper, Bernd, et al. "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)." Annals of Surgical Oncology 23.6 (2016): 1924-7.
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