e23523 Background: Soft tissue sarcomas (STS) comprise a heterogeneous group of malignancies with limited biomarkers for real-time disease monitoring. Circulating tumor DNA (ctDNA) represents a minimally invasive approach to assess tumor burden and treatment response; however, its clinical utility in STS remains incompletely defined. We evaluated ctDNA dynamics across diverse STS subtypes in a real-world clinical cohort. Methods: We retrospectively analyzed plasma-derived ctDNA from 57 patients with STS enrolled in a prospective EHR-based Comprehensive Bone and Soft Tissue Tumor Registry (NCT02677961) at The Ohio State University Comprehensive Cancer Center. ctDNA was assessed using Tempus (n = 34) and Signatera (n = 23) platforms. ctDNA levels were compared with radiographic tumor volume, histologic grade, and disease stage. Tumor burden was quantified using volumetric imaging, and clinical response was assessed by RECIST criteria or physician evaluation. Serial ctDNA measurements were available for a subset of patients. Results: ctDNA was detectable in over 75% of patients. ctDNA levels strongly correlated with tumor volume in both the Signatera (Spearman r = 0.84, p = 2.04 × 10⁻⁹) and Tempus (Spearman r = 0.63, p = 0.0375) cohorts. ctDNA detection was significantly associated with higher histologic grade (p = 0.0217), with Grade 3 tumors demonstrating the highest detection rates. ctDNA presence was not associated with surgical stage (p = 0.666). Among 20 patients with serial sampling, ctDNA dynamics closely mirrored changes in tumor burden during surgery, chemotherapy, and radiation. The sensitivity of ctDNA detection in patients with radiographically evident disease was 79.2%, and in 82% of cases, increases in ctDNA levels preceded radiographic evidence of disease progression across histological subtypes. Conclusions: In this real-world STS cohort, ctDNA levels were associated with tumor burden, histologic grade, and longitudinal treatment response across multiple sarcoma subtypes and assay platforms, with ctDNA increases frequently preceding radiographic disease progression. These findings support ctDNA as a promising biomarker for real-time disease monitoring in STS and provide a rationale for incorporation into prospective sarcoma clinical trials. Larger, multi-institutional studies are warranted to validate these observations.
Sheel et al. (2026) studied this question.