{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T02:03:17Z","timestamp":1784167397562,"version":"3.55.0"},"reference-count":56,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Bone and soft-tissue sarcomas are rare, heterogeneous malignancies whose surveillance remains dominated by imaging despite substantial molecular diversity and variable patterns of relapse. Circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) offer minimally invasive approaches for monitoring tumor biology, but their performance in sarcoma depends strongly on subtype, disease burden, assay design, and biological shedding. Methods: This narrative review synthesizes evidence published from 2015 to 2026 on ctDNA and CTCs for baseline risk assessment, treatment-response monitoring, minimal residual disease (MRD) detection, molecular relapse, and integration with imaging-based surveillance in bone and soft-tissue sarcomas. Results: Current evidence supports a genomics-guided framework in which liquid-biopsy strategy is selected according to sarcoma subtype, molecular architecture, and clinical purpose. ctDNA is the most mature analyte, with best-supported evidence in osteosarcoma, where tumor-informed assays predict postoperative relapse, and in translocation-associated sarcomas, where breakpoint-guided assays enable highly specific longitudinal monitoring. Copy-number-based approaches are relevant for complex-karyotype tumors, while mutation-, methylation-, fragmentomic-, and RNA-based strategies may be useful in selected contexts. However, detection rates vary, false-negative results occur in low-shedding or low-volume disease, and clinical utility for changing treatment remains incompletely established. CTCs provide complementary cellular and prognostic information, particularly in osteosarcoma, but remain limited by platform heterogeneity and incomplete standardization. Conclusion: Liquid biopsy may refine risk stratification, support treatment-response assessment, clarify indeterminate imaging findings, and identify molecular relapse in selected sarcoma patients. At present, it should be interpreted as an adjunct to imaging and specialist multidisciplinary care rather than as a replacement for standard radiologic surveillance.<\/jats:p>","DOI":"10.3390\/cells15141271","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:05:07Z","timestamp":1784163907000},"page":"1271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6854-7041","authenticated-orcid":false,"given":"Ibrahim","family":"Alabid","sequence":"first","affiliation":[{"name":"MBBS, RAK College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University (RAKMHSU), Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Jad","family":"Yousef","sequence":"additional","affiliation":[{"name":"Department of Surgery, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6948-3619","authenticated-orcid":false,"given":"Mohamedanas Mohamedfaruk","family":"Patni","sequence":"additional","affiliation":[{"name":"Department of Community Medicine, RAK College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9497-3781","authenticated-orcid":false,"given":"Radwan Abdulaziz","family":"Aloti","sequence":"additional","affiliation":[{"name":"MBBS, RAK College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University (RAKMHSU), Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zain Al-Abdeen Mohammed","family":"Qassim","sequence":"additional","affiliation":[{"name":"MBBS, RAK College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University (RAKMHSU), Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman Ahmad","family":"Alothman-Agha","sequence":"additional","affiliation":[{"name":"MBBS, RAK College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University (RAKMHSU), Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham Amin","family":"Hamdy","sequence":"additional","affiliation":[{"name":"Department of Surgery, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feras Mohammed","family":"Noury","sequence":"additional","affiliation":[{"name":"Consultant Orthopaedic and Joint Replacement Surgeon, Department of Spine and Orthopaedic Surgery, RAK Hospital, Ras Al Khaimah 11393, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Tarek","family":"Abdelfattah","sequence":"additional","affiliation":[{"name":"MBBS, RAK College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University (RAKMHSU), Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1016\/j.annonc.2021.08.1995","article-title":"Bone sarcomas: ESMO-EURACAN-GENTURIS-ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"32","author":"Strauss","year":"2021","journal-title":"Ann. 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