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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 6/2016

01-06-2016 | Bone and Soft Tissue Sarcomas

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)

Authors: Bernd Kasper, MD, PhD, Viktor Gruenwald, MD, PhD, Peter Reichardt, MD, Sebastian Bauer, MD, PhD, Peter Hohenberger, MD, PhD, Florian Haller, MD, PhD

Published in: Annals of Surgical Oncology | Issue 6/2016

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.
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Metadata
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)
Authors
Bernd Kasper, MD, PhD
Viktor Gruenwald, MD, PhD
Peter Reichardt, MD
Sebastian Bauer, MD, PhD
Peter Hohenberger, MD, PhD
Florian Haller, MD, PhD
Publication date
01-06-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 6/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5132-4

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