Detecting ctDNA Using Personalized Structural Variants to Forecast Recurrence in Localized Soft-Tissue Sarcoma

Area of Science:

• Oncology
• Molecular Diagnostics
• Genomics

Background:

• Soft tissue sarcoma (STS) is a complex cancer with frequent structural variants (SVs).
• Localized STS recurrence rates remain high despite surgery and radiation, with controversial adjuvant therapy roles.
• Assessing circulating tumor DNA (ctDNA) for molecular residual disease detection is crucial.

Purpose of the Study:

• To evaluate the feasibility and sensitivity of tracking tumor-informed SVs via ctDNA in localized STS.
• To correlate ctDNA dynamics with clinical outcomes during perioperative and surveillance periods.
• To inform future adjuvant systemic therapy trials for localized STS.

Main Methods:

• Personalized assays targeting 4-16 SV-breakpoints were developed for ctDNA detection.
• Blood samples were collected from localized, high-risk STS patients at diagnosis, post-radiation, and postoperatively (≤8 weeks).
• ctDNA levels were monitored longitudinally and correlated with radiologic surveillance and clinical outcomes.

Main Results:

• The SV-based ctDNA assay demonstrated 97% sensitivity at baseline in 32 STS patients.
• Postoperative ctDNA detection (≤8 weeks) in 18% of patients predicted early metastatic recurrence within one year.
• ctDNA negativity in the postoperative window was associated with delayed recurrence, preceded by detectable ctDNA.

Conclusions:

• SV-based ctDNA detection is a sensitive and feasible method for localized STS.
• Early postoperative ctDNA detection is a strong indicator of imminent metastatic recurrence.
• These findings support the use of ctDNA in designing personalized adjuvant therapy trials for STS.