Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas

Area of Science:

• Oncology
• Molecular Diagnostics
• Genomics

Background:

• Bone and soft-tissue sarcomas are rare, heterogeneous cancers with diverse relapse patterns.
• Current surveillance relies heavily on imaging, despite advances in understanding tumor biology.
• Minimally invasive methods like circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) show potential for monitoring sarcoma.

Purpose of the Study:

• To review evidence on ctDNA and CTCs for sarcoma surveillance from 2015-2026.
• To assess their utility in risk assessment, treatment response, minimal residual disease (MRD) detection, and molecular relapse.
• To evaluate their integration with current imaging-based surveillance strategies.

Main Methods:

• Narrative review of studies published between 2015 and 2026.
• Focus on ctDNA and CTCs in bone and soft-tissue sarcomas.
• Analysis of applications including risk stratification, treatment monitoring, MRD detection, and relapse identification.

Main Results:

• A genomics-guided liquid biopsy approach is recommended, tailored to sarcoma subtype and molecular characteristics.
• ctDNA assays, particularly tumor-informed and breakpoint-guided, show strong evidence in osteosarcoma and translocation-associated sarcomas.
• Detection rates vary, with limitations in low-volume disease; CTCs offer complementary data but face standardization challenges.

Conclusions:

• Liquid biopsy can enhance risk stratification, treatment assessment, and molecular relapse detection in select sarcoma patients.
• It serves as an adjunct to imaging and multidisciplinary care, not a replacement for standard radiologic surveillance.
• Further standardization and validation are needed to fully establish clinical utility.