Personalized Circulating Tumor DNA Analysis for Predicting Outcomes and Tracking Response to Radiotherapy and Pembrolizumab in Localized Sarcomas: Analysis of the SU2C-SARC032 Trial.

In 30 seconds

This analysis of the SU2C-SARC032 phase II randomised trial evaluated personalized circulating tumour DNA (ctDNA) profiling in 106 patients with high-risk, localized soft tissue sarcoma treated with preoperative radiotherapy, with or without perioperative pembrolizumab. Baseline ctDNA was detected in 85% of patients. ctDNA levels before treatment, after neoadjuvant therapy and before surgery, and after surgery were associated with disease-free and overall survival in adjusted as well as unadjusted analyses. Patients receiving pembrolizumab had a greater post-neoadjuvant ctDNA decrease, alongside significantly better disease-free survival.

Key findings

• Personalized ctDNA profiling detected baseline ctDNA in 85% of patients.
• ctDNA levels at pretreatment, presurgery after neoadjuvant therapy, and postsurgery were associated with disease-free and overall survival in multivariable analyses.
• Patients treated with pembrolizumab had a greater ctDNA decrease after neoadjuvant therapy and significantly better disease-free survival.
• Detection of multiple tumour clones by ctDNA after surgery was associated with inferior outcomes.

Why it matters

Localized soft tissue sarcomas can be difficult to monitor with ctDNA because they are rare, heterogeneous tumours with low mutational burden. These findings suggest that personalized, tumour-informed assays can detect ctDNA and provide prognostic information across the perioperative course, including after surgery. This may help inform research into molecular monitoring and risk assessment in this population.

What to keep in mind

This was an analysis of a phase II trial, and the findings support prospective ctDNA-guided trials rather than establishing clinical utility for ctDNA-directed decisions.