Advancing precision oncology in soft tissue sarcomas: The role of iTRAC in metastatic risk stratification and treatment personalization.

Abstract

11534 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 distribution 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 analysis was performed to evaluate the iTRAC compared to FNCLCC and CINSARC for metastatic risk stratification. Results: STS patients with medium iTRAC level 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 molecular and histological prognosis systems like CINSARC and FNCLCC grade by revealing distinct MFS between patients receiving or not chemotherapy. This could enable 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 integration for patients care.