Extraskeletal osteosarcoma harboring ETV6::NTRK3 fusion treated successfully with larotrectinib: a case study

Area of Science:

• Oncology
• Genetics
• Precision Medicine

Background:

• Extraskeletal osteosarcoma (ESOS) is a rare, aggressive tumor with limited treatment options and poor prognosis.
• Identifying targetable genetic alterations is crucial for improving ESOS treatment outcomes.
• This study reports the first global case of ESOS with an ETV6::NTRK3 fusion.

Purpose of the Study:

• To report the first worldwide case of extraskeletal osteosarcoma (ESOS) harboring an ETV6::NTRK3 fusion.
• To describe the clinical response to larotrectinib, a selective tropomyosin receptor kinase (TRK) inhibitor, in this patient.

Main Methods:

• A case report detailing a 74-year-old male with a large, inoperable neck tumor.
• Histopathological, immunohistochemical, and molecular analyses, including targeted RNA sequencing and DNA-based targeted analysis.
• Monitoring of the clinical course over an 8-month treatment period with larotrectinib.

Main Results:

• An actionable ETV6::NTRK3 fusion, previously undescribed in ESOS, was identified.
• Larotrectinib treatment resulted in a rapid clinical response within 3 weeks, with partial remission observed.
• Tumor shrinkage continued over 8 months, with no significant adverse effects related to TRK inhibition despite other medical complications.

Conclusions:

• This case is the first reported instance of extraskeletal osteosarcoma (ESOS) with an NTRK fusion.
• The patient demonstrated a rapid and sustained response to larotrectinib, showcasing its efficacy.
• Molecular profiling is vital for identifying actionable targets in rare and aggressive tumors like ESOS.