Abstract 1534P
Background
Infantile fibrosarcoma (IFS) is a very rare subtype that display NTRK fusion in more than 90% of the cases. NTRK fusions may be present at very low frequency in many other sarcoma subtypes. Natural history of those NTRK-fusion positive sarcomas (NPS) remains unclear. This retrospective study aims to describe the clinical characteristics of NPS patients.
Methods
This study was performed between March 2019 and March 2021 at Centers L Bérard and O Lambret (France) as a retrospective translational research program. Tumor samples were tested for NTRK gene fusions using RNA-sequencing, from i/ a retrospective cohort of 500 soft tissue sarcoma (excluding IFS) of the NETSARC database, ii/ prospectively in routine practice and iii/ from RNASarc molecular screening program (NCT03375437). RNA seq was performed on FFPE samples using TruSeq RNA Access Library Prep Kit (Illumina®, San Diego, USA). Patients and tumors characteristics were collected from medical record.
Results
Overall, 10 NPS patients were identified, including 5 from the retrospective case series (N=5/500, 1%). The sex ratio was 1,5 and the median age at diagnosis was 51,5 years [1-78]. Represented histotypes were IMT (N=3), dedifferentiated liposarcoma (N=2), quadruple wild-type GIST (N=1), uterine spindle cell sarcoma (N=1), leiomyosarcoma (N=1), UPS (N=1) and the recently described NTRK-rearranged spindle cell neoplasm (N=1). Five patients had a metastatic disease, 1 synchronous (uterine sarcoma) and 4 metachronous (liposarcoma, leiomyosarcoma, UPS and GIST) with a median overall survival from metastasis diagnosis of 17 months (range 6-25). None of these 5 metastatic patients were treated with a TRK inhibitor. Two patients had locally advanced disease at diagnosis and both were treated with a TRK inhibitor leading to complete response in one case (2 years of ongoing treatment) and partial response allowing surgical resection for the other. The 3 remaining patients had no relapse after localized tumor resection.
Conclusions
This series confirms the heterogeneity of NPS and suggests a poor prognosis in the metastatic setting, similar to that of other soft tissue sarcomas. Altogether, our findings provide more evidence that supports targeted therapy for NPS.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Bayer, Roche.
Disclosure
All authors have declared no conflicts of interest.