{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:18:09Z","timestamp":1792181889284,"version":"4.4.0"},"reference-count":30,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"35","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2025,12,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Identifying discrete subgroups associated with treatment response and resistance in localized Ewing sarcoma (EWS) remains a challenge. The primary objective of the Children's Oncology Group (COG) biology study AEWS18B1-Q was to molecularly characterize patients with localized EWS on prospective modern-day trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>\n                      We analyzed clinical and molecular features from patients with localized EWS enrolled on frontline COG trials. All patients had available formalin-fixed paraffin-embedded (FFPE) tissue, frozen tissue, or whole-genome\u2013amplified material. Sequencing was performed for identification of canonical fusions, recurrent copy number alterations (CNAs), and alterations in\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">STAG2<\/jats:italic>\n                      . Available tissue was analyzed for loss of STAG2 protein expression. Molecular features were evaluated for their association with cumulative incidence of relapse in univariate and multivariable analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Three hundred fifty-one patients had sufficient tissue, which in most cases was extracted from two FFPE slides. EWS canonical fusions were identified in 282 patients (80.3%). Pathogenic mutations in\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">STAG2<\/jats:italic>\n                      were identified in 5.1% and 7.6% of patients, respectively. A total of 63.1% of patients were found to have recurrent CNAs. In univariate analysis, there was an increased cumulative incidence of relapse in patients with\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      mutation (5-year cumulative incidence of relapse 43%, 95% CI [17% to 67%]\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      22%, 95% CI [17% to 27%]; Gray's test\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .039),\n                      <jats:italic toggle=\"yes\">STAG2<\/jats:italic>\n                      mutation (53%, 95% CI [29% to 73%]\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      21%, 95% CI [16% to 26%];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001), and recurrent CNAs (30%, 95% CI [22% to 37%]\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      16%, 95% CI [9% to 24%];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .005). In a multivariable analysis,\n                      <jats:italic toggle=\"yes\">STAG2<\/jats:italic>\n                      mutation was the only molecular biomarker that remained prognostic.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      This is a prospective validation of the molecular prognostic features of patients with localized EWS receiving standard-of-care therapy on therapeutic clinical trials. Building on previous work, patients with\n                      <jats:italic toggle=\"yes\">STAG2<\/jats:italic>\n                      mutations were at high risk of relapse.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-00157","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T21:00:28Z","timestamp":1762203628000},"page":"3750-3759","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":15,"title":["Molecular Characterization Informs Prognosis in Patients With Localized Ewing Sarcoma: A Report From the Children's Oncology Group"],"prefix":"10.1200","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8643-2725","authenticated-orcid":true,"given":"Riaz","family":"Gillani","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Boston Children's Hospital, Boston, MA"},{"name":"Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Shulman","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Boston Children's Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8139-9839","authenticated-orcid":true,"given":"Natalie J.","family":"DelRocco","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-2003","authenticated-orcid":true,"given":"Kelly","family":"Klega","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Boston Children's Hospital, Boston, MA"},{"name":"Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxu","family":"Han","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":"Mark D.","family":"Krailo","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":"Jonathan C.","family":"Slack","sequence":"additional","affiliation":[{"name":"Robert J. Tomsich Institute of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6498-1181","authenticated-orcid":true,"given":"Mohammad","family":"Tanhaemami","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Boston Children's Hospital, Boston, MA"},{"name":"Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Boston Children's Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Bainer","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Boston Children's Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1202-5603","authenticated-orcid":true,"given":"Cora","family":"Ricker","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Boston Children's Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josee","family":"Sparks","sequence":"additional","affiliation":[{"name":"Biopathology Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3925-3243","authenticated-orcid":true,"given":"Kelly M.","family":"Bailey","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8238-2465","authenticated-orcid":true,"given":"Damon R.","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0882-738X","authenticated-orcid":true,"given":"Steven G.","family":"DuBois","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"},{"name":"Boston Children's Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0541-2536","authenticated-orcid":true,"given":"Patrick","family":"Leavey","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX"},{"name":"Children's Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7790-0777","authenticated-orcid":true,"given":"Leo","family":"Mascarenhas","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1071-4563","authenticated-orcid":true,"given":"Patrick J.","family":"Grohar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Michigan Medical 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