Prognostic significance of tumor fraction in advanced sarcoma: highlighting a novel circulating biomarker

Circulating tumor DNA (ctDNA) tumor fraction (TF), the proportion of ctDNA within total cell-free DNA, is emerging as a simple and powerful biomarker across cancers. While recent studies in carcinomas established its prognostic value, its role in sarcomas remains unknown. We analyzed 192 patients with advanced soft tissue sarcomas enrolled in the French BIP (NCT02534649) and STING (NCT04932525) precision medicine programs, using the FoundationOne^® Liquid CDx assay to quantify TF. Patients were stratified at a 10% cutpoint, consistent with prior reports. Median overall survival was 6.3 months for patients with TF ≥ 10% compared to 12.9 months for those with TF < 10% (p = 0.01). On multivariate analysis adjusting for histology, grade, performance status, and metastatic burden, high TF remained an independent predictor of poor survival (HR 2.0, 95% CI 1.1-3.5, p = 0.017). Unlike carcinomas, sarcomas currently lack validated circulating biomarkers. Our findings demonstrate that ctDNA TF provides non-invasive, real-time prognostic information in this rare and heterogeneous tumor type, with potential applications for patient stratification, treatment planning, and clinical trial design. Prospective validation is warranted to define standardized TF thresholds and support its integration into sarcoma care.