The Circulating Nucleic Acid Characteristics of Non-Metastatic Soft Tissue Sarcoma Patients

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Soft tissue sarcomas (STS) are rare cancers with poor prognoses.
• Effective monitoring tools for non-metastatic STS during curative treatment are limited.

Purpose of the Study:

• To investigate the potential of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) for tracking soft tissue sarcoma patients.
• To assess the diagnostic and prognostic value of cfDNA and ctDNA in STS.

Main Methods:

• Analysis of cfDNA levels in 29 STS patients undergoing curative treatment.
• Characterization of ctDNA using amplicon panels and droplet digital PCR (ddPCR) assays.
• Whole exome sequencing (WES) to identify patient-specific mutations for ctDNA tracking.

Main Results:

• Perioperative cfDNA levels showed a trend towards elevation but lacked correlation with tumor characteristics or recurrence.
• Initial ctDNA detection rates were low (2.5%) with standard amplicon panels.
• Custom ddPCR and Ion AmpliSeq™ panels identified ctDNA in 17% of patients, with early detection before radiological recurrence in two cases.
• The majority of patients (83%) did not show detectable ctDNA, indicating limitations of current methods.

Conclusions:

• cfDNA analysis has limited diagnostic or prognostic value in non-metastatic STS.
• Current ctDNA detection methods show promise but are not yet sufficiently sensitive for routine monitoring of all STS patients.
• Significant advancements are required to establish circulating nucleic acids as a reliable tool for tracking STS patients during treatment and follow-up.