Abstract 82P
Background
Soft Tissue Sarcomas (STS), known for their extensive Genomic instability (GIN), often result in poor clinical outcomes. grading systems, such as FNCLCC, have limited prognostic accuracy in stratifying metastatic risk for STS patients. We introduce transcription-associated GIN indice (iTRAC) to improve prognostic precision and guide treatment decisions.
Methods
This study analyzed 226 STS tumor samples using RNA sequencing (RNAseq) to assess breakpoint (BP) distributions from fusion transcripts as a surrogate for GIN. We calculated iTRAC to quantify transcription--associated GIN. Kaplan-Meier survival analysis were used to evaluate prognostic relevance in patients receiving or not chemotherapy. Multivariate analyses were performed to evaluate the iTRAC compared to FNCLCC and CINSARC for metastatic risk stratification.
Results
STS patients with medium iTRAC levels had the poorest metastasis-free survival (MFS) compared to low and high iTRAC levels. Importantly, patients with low iTRAC have a poorer outcome when treated with chemotherapy than those untreated, but at the contrary patients with medium iTRAC and treated by chemotherapy have a better outcome, raising the question of the potential predictive value of iTRAC for adjuvant chemotherapy in STS patients. FNCLCC and CINSARC groups did not show significant difference in MFS between treated and not treated patients.
Conclusions
iTRAC is a novel biomarker for stratifying metastatic risk and guiding personalized treatment in STS. It outperforms systems like CINSARC and FNCLCC by distinguishing low- and medium-iTRAC groups, revealing distinct MFS between patients receiving or not chemotherapy. This enables better identification of patients who may benefit from chemotherapy and alternative options for those with poor responses. Prospective clinical trials are needed for validation and routine integration.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
INSERM.
Funding
INSERM, ICGC.
Disclosure
A. Benhaddou: Financial Interests, Personal and Institutional, Stocks/Shares: Magic Genomix. All other authors have declared no conflicts of interest.