{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:45:38Z","timestamp":1792010738277,"version":"4.4.0"},"reference-count":19,"publisher":"American Society of Clinical Oncology (ASCO)","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Identification of discrete risk groups remains a high priority for patients with Ewing sarcoma (EWS). We sought to prospectively validate circulating tumor DNA (ctDNA) as a prognostic factor and develop clinical-molecular risk groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We conducted a prospective investigator-initiated biology study for patients with localized EWS (LEOPARD) and embedded ctDNA analysis into the North American frontline metastatic study AEWS1221. Eligible patients were younger than 50 years with newly diagnosed EWS. All patients provided a baseline blood sample for analysis, which was subjected to ultralow-pass whole-genome sequencing and hybrid capture panel sequencing for ctDNA quantification, fusion detection, and characterization of\n                      <jats:italic toggle=\"yes\">STAG2<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      alterations. Serial ctDNA sequencing was conducted on a subset of patients in each study. We tested for associations between ctDNA burden and secondary genomic events, and clinical features and outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      One hundred forty patients with localized disease and 255 with metastatic disease provided evaluable pretreatment samples for ctDNA analysis. Elevated baseline ctDNA was associated with stage, tumor size, primary site, indeterminate pulmonary nodules, and metastatic pattern. Elevated pretreatment ctDNA burden was associated with inferior outcomes in patients with localized (n = 140, hazard ratio [HR] = 2.36,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .032) and metastatic disease (n = 255, HR = 2.15,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .001). Patients with metastatic disease and\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      variants and\/or persistent on-therapy ctDNA had dismal outcomes. Patients with localized disease, low ctDNA, small tumors, and favorable genomics had no events and constitute a novel low-risk group. Among patients with metastatic disease, those with lung-only disease, low ctDNA, and favorable genomics represent an intermediate-risk group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>This study prospectively validates pretreatment ctDNA burden as prognostic in EWS. Risk groups that integrate ctDNA burden with clinical-molecular features differentiate patients with low-, intermediate-, and high-risk disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-26-00285","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:00:16Z","timestamp":1789502416000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Tumor DNA Profiling Defines Risk Classification in Patients With Ewing Sarcoma: A Report From the Children's Oncology Group and the LEOPARD Study"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5994-2604","authenticated-orcid":false,"given":"David S.","family":"Shulman","sequence":"first","affiliation":[{"name":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-2003","authenticated-orcid":false,"given":"Kelly","family":"Klega","sequence":"additional","affiliation":[{"name":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA"},{"name":"Broad Institute of Harvard and MIT, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Chen","sequence":"additional","affiliation":[{"name":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Buxton","sequence":"additional","affiliation":[{"name":"Children's Oncology Group, Monrovia, CA"},{"name":"Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot","family":"Gohn","sequence":"additional","affiliation":[{"name":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9880-3356","authenticated-orcid":false,"given":"Sarah","family":"Sexton","sequence":"additional","affiliation":[{"name":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Clinton","sequence":"additional","affiliation":[{"name":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA"},{"name":"Broad Institute of Harvard and MIT, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6498-1181","authenticated-orcid":false,"given":"Mohammad","family":"Tanhaemami","sequence":"additional","affiliation":[{"name":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA"},{"name":"Broad Institute of Harvard and MIT, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Cibulskis","sequence":"additional","affiliation":[{"name":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA"},{"name":"Broad Institute of Harvard and MIT, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9896-8084","authenticated-orcid":false,"given":"Edwin","family":"Choy","sequence":"additional","affiliation":[{"name":"Mass General Brigham Cancer Institute, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1128-784X","authenticated-orcid":false,"given":"Thomas","family":"Cash","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine, Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1788-5832","authenticated-orcid":false,"given":"Kris Ann P.","family":"Schultz","sequence":"additional","affiliation":[{"name":"Cancer and Blood Disorders, Children's Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7790-0777","authenticated-orcid":false,"given":"Leo","family":"Mascarenhas","sequence":"additional","affiliation":[{"name":"Guerin Children's and Cedars-Sinai Cancer, Cedars Sinai Health Sciences University, Los Angeles, 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WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3926-1446","authenticated-orcid":false,"given":"Michael W.","family":"Bishop","sequence":"additional","affiliation":[{"name":"St Jude Children's Research Hospital, Memphis, TN, USA;"},{"name":"Arkansas Children's Hospital, Little Rock, AR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avanthi Tayi","family":"Shah","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8739-9100","authenticated-orcid":false,"given":"Luke D.","family":"Maese","sequence":"additional","affiliation":[{"name":"University of Utah, Huntsman Cancer Institute, and Primary Children's Hospital, Salt Lake City, 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Report on the Natural Duration of Cancer","author":"Greenwood M","year":"1926","unstructured":"Greenwood M: A Report on the Natural Duration of Cancer, Volume 33. 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