Top Line: Is circulating tumor DNA (ctDNA) prognostic of outcomes for patients treated with neoadjuvant therapy for soft tissue sarcoma (STS)?
The Study: However, ctDNA assays often rely on recurrent hotspot point mutations that aren’t common in STS. STS is very heterogeneous, typically shed little DNA, and are driven by genomic changes that are difficult to detect. This analysis from the SU2C-SARC032 trial collected plasma samples from 106 patients with undifferentiated pleomorphic sarcoma or pleomorphic/dedifferentiated liposarcoma of the extremity or limb girdle at baseline, after neoadjuvant radiation +/- pembro, and after surgery. Using personalized panels, ctDNA was detected in 85% of patients at baseline, and ctDNA levels were associated with tumor size and grade. ctDNA levels at all time points before, during, and after treatment were strongly associated with survival outcomes. In most patients, ctDNA declined after neoadjuvant therapy, but the decline was greater in those who received pembro. Finally, detection of ctDNA 3 months after surgery was associated with significantly worse DFS and OS
TBL: In this study using personalized ctDNA profiling, ctDNA levels and changes in ctDNA were prognostic of survival outcomes among patients receiving neoadjuvant therapy for sarcoma. | Subramanian, J Clin Oncol 2026
The Study: However, ctDNA assays often rely on recurrent hotspot point mutations that aren’t common in STS. STS is very heterogeneous, typically shed little DNA, and are driven by genomic changes that are difficult to detect. This analysis from the SU2C-SARC032 trial collected plasma samples from 106 patients with undifferentiated pleomorphic sarcoma or pleomorphic/dedifferentiated liposarcoma of the extremity or limb girdle at baseline, after neoadjuvant radiation +/- pembro, and after surgery. Using personalized panels, ctDNA was detected in 85% of patients at baseline, and ctDNA levels were associated with tumor size and grade. ctDNA levels at all time points before, during, and after treatment were strongly associated with survival outcomes. In most patients, ctDNA declined after neoadjuvant therapy, but the decline was greater in those who received pembro. Finally, detection of ctDNA 3 months after surgery was associated with significantly worse DFS and OS
TBL: In this study using personalized ctDNA profiling, ctDNA levels and changes in ctDNA were prognostic of survival outcomes among patients receiving neoadjuvant therapy for sarcoma. | Subramanian, J Clin Oncol 2026