Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Skok, K; Ochsenhofer, F; Gassner, R; Leithner, A; Szkandera, J; Viertler, C; Hasenschwandtner, S; Reichinger, A; Liegl-Atzwanger, B.
Extraskeletal osteosarcoma harboring ETV6::NTRK3 fusion treated successfully with larotrectinib: a case study.
Commun Med (Lond). 2025; 5(1):489
Doi: 10.1038/s43856-025-01184-z
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- Führende Autor*innen der Med Uni Graz
- Liegl-Atzwanger Bernadette
- Skok Kristijan
- Co-Autor*innen der Med Uni Graz
- Gassner Raphael
- Leithner Andreas
- Szkandera Joanna
- Viertler Christian
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- Abstract:
- BACKGROUND: Extraskeletal osteosarcoma (ESOS) is a rare, aggressive mesenchymal tumor with limited therapeutic options and a poor prognosis due to frequent metastases. Identifying targetable genetic alterations could improve treatment outcomes. The objective is to report the first worldwide case of ESOS harboring an ETV6::NTRK3 fusion and describe the clinical response to larotrectinib, a selective TRK inhibitor. METHODS: Case report of a 74-year-old man with a rapidly enlarging, inoperable neck tumor measuring 7.9 ×7.1 ×6.6 cm. The case underwent histopathological, immunohistochemical, and molecular analyses, including targeted RNA sequencing using the Archer Fusion Plex Pan Solid Tumor v2 panel and DNA-based targeted analysis with the Ion Torrent Oncomine Comprehensive Assay Plus. The clinical course was monitored over an 8-month treatment period. RESULTS: Molecular analysis revealed an actionable, in ESOS previously not described, ETV6::NTRK3 fusion. Treatment with larotrectinib (100 mg twice daily) led to a rapid clinical response within 3 weeks. MRI demonstrated partial remission after 2 months (4.7 ×3.9 ×2.8 cm), with further tumor shrinkage at 8 months (4.4 ×3.7 ×2.4 cm). Despite complications, including urothelial carcinoma recurrence requiring chemotherapy and surgery, larotrectinib was resumed with dose adjustments. No significant adverse effects related to TRK inhibition were observed. CONCLUSIONS: This case represents the first reported instance of ESOS with an NTRK fusion. The rapid and sustained response to larotrectinib highlights the potential of precision medicine in managing rare and aggressive tumors, emphasizing the importance of molecular profiling to identify actionable targets.