Correlation of CTNNB1 mutation status with progression arrest rate in RECIST progressive desmoid-type fibromatosis treated with imatinib

• Verfasst von: Kasper, Bernd [VerfasserIn]
• Verfasst von: Hohenberger, Peter [VerfasserIn]
• Titel: Correlation of CTNNB1 mutation status with progression arrest rate in RECIST progressive desmoid-type fibromatosis treated with imatinib
• Titelzusatz: translational research results from a phase 2 study of the German Interdisciplinary Sarcoma Group (GISG-01)
• Verf.angabe: Bernd Kasper, MD, PhD, Viktor Gruenwald, MD, PhD, Peter Reichardt, MD, Sebastian Bauer, MD, PhD, Peter Hohenberger, MD, PhD, and Florian Haller, MD, PhD
• E-Jahr: 2016
• Jahr: 9 February 2016
• Umfang: 4 S.
• Fussnoten: Gesehen am 18.06.2019
• Titel Quelle: Enthalten in: Annals of surgical oncology
• Ort Quelle: Berlin [u.a.] : Springer, 1994
• Jahr Quelle: 2016
• Band/Heft Quelle: 23(2016), 6, Seite 1924-1927
• ISSN Quelle: 1534-4681
• DOI: doi:10.1245/s10434-016-5132-4
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Desmoid Tumor
• Sach-SW: Imatinib
• Sach-SW: Meloxicam
• Sach-SW: Pazopanib
• Sach-SW: Sorafenib
• K10plus-PPN: 1667628100

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.