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This prospective observational study sought to ascertain the feasibility of ctDNA detection in patients with hepatoblastoma and explore its associations with established clinical indicators and biomarkers, including serum Alpha-fetoprotein (AFP). We obtained 38 plasma samples and 17 tumor samples from 20 patients with hepatoblastoma. These samples were collected at various stages: 10 at initial diagnosis, 17 during neoadjuvant chemotherapy, 6 post-operatively, and 5 at disease recurrence. Utilizing a bespoke sequencing assay we developed called QUENCH, we identified single nucleotide variants and deletions in CTNNB1 ctDNA. Our study demonstrated the capability to quantitate ctDNA down to a variant allele frequency of 0.3%, achieving a sensitivity of 90% for patients at initial diagnosis, and a specificity of 100% at the patient level. Notably, ctDNA positivity correlated with tumor burden, and ctDNA levels exhibited associations with macroscopic residual disease and treatment response. Our findings provide evidence for the utility of quantitative ctDNA detection in hepatoblastoma management. Given the distinct detection targets, ctDNA and AFP-based stratification and monitoring approaches could synergize to enhance clinical decision-making. Further research is needed to elucidate the interplay between ctDNA and AFP and determine the optimal clinical applications for both methods in risk stratification and residual disease detection.<\/jats:p>","DOI":"10.3390\/cancers16010012","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T11:17:24Z","timestamp":1702984644000},"page":"12","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Quantitative ctDNA Detection in Hepatoblastoma: Implications for Precision Medicine"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2869-4310","authenticated-orcid":false,"given":"Smadar","family":"Kahana-Edwin","sequence":"first","affiliation":[{"name":"Children\u2019s Cancer Research Unit, Kids Research, The Children\u2019s Hospital at Westmead, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Torpy","sequence":"additional","affiliation":[{"name":"Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1734-2707","authenticated-orcid":false,"given":"Lucy E.","family":"Cain","sequence":"additional","affiliation":[{"name":"Cancer Centre for Children, The Children\u2019s Hospital at Westmead, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2409-4622","authenticated-orcid":false,"given":"Anna","family":"Mullins","sequence":"additional","affiliation":[{"name":"Cancer Centre for Children, The Children\u2019s Hospital at Westmead, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"McCowage","sequence":"additional","affiliation":[{"name":"Cancer Centre for Children, The Children\u2019s Hospital at Westmead, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Woodfield","sequence":"additional","affiliation":[{"name":"Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children\u2019s Surgical Oncology Program, Texas Children\u2019s Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev A.","family":"Vasudevan","sequence":"additional","affiliation":[{"name":"Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children\u2019s Surgical Oncology Program, Texas Children\u2019s Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7221-6199","authenticated-orcid":false,"given":"Dan P. T.","family":"Shea","sequence":"additional","affiliation":[{"name":"Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre E.","family":"Minoche","sequence":"additional","affiliation":[{"name":"Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres F.","family":"Espinoza","sequence":"additional","affiliation":[{"name":"Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children\u2019s Surgical Oncology Program, Texas Children\u2019s Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kummerfeld","sequence":"additional","affiliation":[{"name":"Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia"},{"name":"St Vincent\u2019s Clinical School, UNSW Sydney, Sydney, NSW 2217, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4645-553X","authenticated-orcid":false,"given":"Leonard D.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia"},{"name":"St Vincent\u2019s Clinical School, UNSW Sydney, Sydney, NSW 2217, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Karpelowsky","sequence":"additional","affiliation":[{"name":"Children\u2019s Cancer Research Unit, Kids Research, The Children\u2019s Hospital at Westmead, Sydney, NSW 2145, Australia"},{"name":"Paediatric Oncology and Thoracic Surgery, The Children\u2019s Hospital at Westmead, Sydney, NSW 2145, Australia"},{"name":"Division of Child and Adolescent Health, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hager, J., and Sergi, C.M.J.E.P. 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