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Liquid biopsy enables residual-disease monitoring, but prior studies report conflicting detection rates and ctDNA levels. In 19 patients, cell-free DNA alongside formalin-fixed paraffin-embedded tumor tissue DNA and leukocyte DNA were sequenced, with baseline and longitudinal cfDNA revealing ctDNA changes consistent with clinical presentation. 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Monitoring helps assess residual disease and treatment effectiveness over time.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What discrepancy did the study try to resolve?",{"text":117,"@type":113},"Previous research showed conflicting detection rates for liquid biopsy and varying ctDNA levels across studies. The work aimed to clarify this mismatch using coordinated sequencing of multiple DNA sources.",{"name":119,"@type":110,"acceptedAnswer":120},"How were patients' samples analyzed to monitor therapy?",{"text":121,"@type":113},"The study sequenced cell-free DNA, formalin-fixed paraffin-embedded tumor tissue DNA, and leukocyte DNA from 19 esophageal cancer patients, using biological or technical duplicate strategies. 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Combining Solid and Liquid Biopsy for Therapy Monitoring in Esophageal Cancer. Int. J. Mol. Sci. 2023, 24, 10673. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms241310673](10.3390/ijms241310673)  \nAcademic Editor: Hidekazu Suzuki  \nReceived: 15 March 2023  \nRevised: 15 June 2023  \nAccepted: 17 June 2023  \nPublished: 26 June 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein Campus Kiel, 24105 Kiel, Germany; fl[orian.richter@uksh.de](orian.richter@uksh.de) (F.R.); [anne-sophie.mehdorn@uksh.de](anne-sophie.mehdorn@uksh.de) (A.-S.M.); [thomas.becker@uksh.de](thomas.becker@uksh.de) (T.B.)  \n2 Institute of Clinical Molecular Biology, Kiel University, 24105 Kiel, Germany; [clara.henssen2@uksh.de](clara.henssen2@uksh.de) (C.H.); [t.steiert@ikmb.uni-kiel.de](t.steiert@ikmb.uni-kiel.de) (T.A.S.); [a.franke@mucosa.de](a.franke@mucosa.de) (A.F.)  \n3 Department of Molecular and Experimental Medicine, Avera Cancer Institute, Sioux Falls, SD 57105, USA; [tobias.meissner@avera.org](tobias.meissner@avera.org)  \n4 Department of Pathology, University Hospital Schleswig-Holstein Campus Kiel, 24105 Kiel, Germany; [christoph.roecken@uksh.de](christoph.roecken@uksh.de)  \n5 Department of Surgery, Israelitisches Krankenhaus Hamburg, 22297 Hamburg, Germany; [j.egberts@ik-h.de](j.egberts@ik-h.de)  \n[6](6 Institute for Experimental Cancer Research)[ Institute for Experimental Cancer Research](6 Institute for Experimental Cancer Research), [Kiel University](Kiel University), [University Hospital Schleswig-Holstein Campus](University Hospital Schleswig-Holstein Campus)[ ](University Hospital Schleswig-Holstein Campus)Kiel, 24105 Kiel, Germany; [susanne.sebens@email.uni-kiel.de](susanne.sebens@email.uni-kiel.de)  \n* Correspondence: m.forster@ikmb.uni-kiel.de; Tel.: +49-431-500-15136  \nAbstract: Esophageal cancer (EC) has one of the highest mortality rates among cancers, making it imperative that therapies are optimized and dynamically adapted to individuals. In this regard, liquid biopsy is an increasingly important method for residual disease monitoring. However, conflicting detection rates (14% versus 60%) and varying cell-free circulating tumor DNA (ctDNA) levels (0.07% versus 0.5%) have been observed in previous studies. Here, we aim to resolve this discrepancy. For 19 EC patients, a complete set of cell-free DNA (cfDNA), formalin-fixed paraffin-embedded tumor tissue (TT) DNA and leukocyte DNA was sequenced (139 libraries) . cfDNA was examined in biological duplicates and/or longitudinally, and TT DNA was examined in technical duplicates. In baseline cfDNA, mutations were detected in 12 out of 19 patients (63%); the median ctDNA level was 0.4% . Longitudinal ctDNA changes were consistent with clinical presentation. Considerable mutational diversity was observed in TT, with fewer mutations in cfDNA. The most recurrently mutated genes in TT were TP53, SMAD4, TSHZ3, and SETBP1, with SETBP1 being reported for the first time. ctDNA in blood can be used for therapy monitoring of EC patients. However, a combination of solid and liquid samples should be used to help guide individualized EC the","cbCaid3Ikd4DDWWV","https://ap.wps.com/l/cbCaid3Ikd4DDWWV","pdf",2369327,17,"English","# Abstract\n# Introduction","[{\"question\":\"Why is therapy monitoring important in esophageal cancer?\",\"answer\":\"Esophageal cancer has a poor prognosis and therapies must be optimized and adapted to individuals. Monitoring helps assess residual disease and treatment effectiveness over time.\"},{\"question\":\"What discrepancy did the study try to resolve?\",\"answer\":\"Previous research showed conflicting detection rates for liquid biopsy and varying ctDNA levels across studies. The work aimed to clarify this mismatch using coordinated sequencing of multiple DNA sources.\"},{\"question\":\"How were patients' samples analyzed to monitor therapy?\",\"answer\":\"The study sequenced cell-free DNA, formalin-fixed paraffin-embedded tumor tissue DNA, and leukocyte DNA from 19 esophageal cancer patients, using biological or technical duplicate strategies. Longitudinal ctDNA changes were then compared with clinical presentation.\"}]","Combining Solid and Liquid Biopsy for Therapy Monitoring in Esophageal Cancer | PDF",1790562266,43]