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)
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...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
9 February 2016
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| In: |
Annals of surgical oncology
Year: 2016, Volume: 23, Issue: 6, Pages: 1924-1927 |
| ISSN: | 1534-4681 |
| DOI: | 10.1245/s10434-016-5132-4 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1245/s10434-016-5132-4
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| Author Notes: | Bernd Kasper, MD, PhD, Viktor Gruenwald, MD, PhD, Peter Reichardt, MD, Sebastian Bauer, MD, PhD, Peter Hohenberger, MD, PhD, and Florian Haller, MD, PhD |
| Summary: | 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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| Item Description: | Gesehen am 18.06.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1534-4681 |
| DOI: | 10.1245/s10434-016-5132-4 |