{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:09:49Z","timestamp":1792595389587,"version":"4.5.0"},"reference-count":28,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"7","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> SJMB03 (ClinicalTrials.gov identifier: NCT00085202 ) was a phase III risk-adapted trial that aimed to determine the frequency and clinical significance of biological variants and genetic alterations in medulloblastoma. <\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p> Patients 3-21 years old were stratified into average-risk and high-risk treatment groups based on metastatic status and extent of resection. Medulloblastomas were molecularly classified into subgroups (Wingless [WNT], Sonic Hedgehog [SHH], group 3, and group 4) and subtypes based on DNA methylation profiles and overlaid with gene mutations from next-generation sequencing. Coprimary study end points were (1) to assess the relationship between ERBB2 protein expression in tumors and progression-free survival (PFS), and (2) to estimate the frequency of mutations associated with WNT and SHH tumors. Clinical and molecular risk factors were evaluated, and the most robust were used to model new risk-classification categories. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> Three hundred thirty eligible patients with medulloblastoma were enrolled. Five-year PFS was 83.2% (95% CI, 78.4 to 88.2) for average-risk patients (n = 227) and 58.7% (95% CI, 49.8 to 69.1) for high-risk patients (n = 103). No association was found between ERBB2 status and PFS in the overall cohort ( P = .74) or when patients were stratified by clinical risk ( P = .71). Mutations in CTNNB1 (96%), DDX3X (37%), and SMARCA4 (24%) were most common in WNT tumors and PTCH1 (38%), TP53 (21%), and DDX3X (19%) in SHH tumors. Methylome profiling classified 53 WNT (17.4%), 48 SHH (15.7%), 65 group 3 (21.3%), and 139 group 4 (45.6%) tumors. A comprehensive clinicomolecular risk factor analysis identified three low-risk groups (WNT, low-risk SHH, and low-risk combined groups 3 and 4) with excellent (5-year PFS &gt; 90%) and two very high-risk groups (high-risk SHH and high-risk combined groups 3 and 4) with poor survival (5-year PFS &lt; 60%). <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> These results establish a new risk stratification for future medulloblastoma trials. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.20.01372","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T21:05:38Z","timestamp":1609967138000},"page":"822-835","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":234,"title":["Outcomes by Clinical and Molecular Features in Children With Medulloblastoma Treated With Risk-Adapted Therapy: Results of an International Phase III Trial (SJMB03)"],"prefix":"10.1200","volume":"39","author":[{"given":"Amar","family":"Gajjar","sequence":"first","affiliation":[{"name":"Division of Neuro Oncology, Department of Oncology, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7441-9486","authenticated-orcid":false,"given":"Giles W.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Division of Neuro Oncology, Department of Oncology, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle S.","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Brain Tumor Research, Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0412-6255","authenticated-orcid":false,"given":"Thomas E.","family":"Merchant","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, St Jude Children's Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murali","family":"Chintagumpala","sequence":"additional","affiliation":[{"name":"Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Su","sequence":"additional","affiliation":[{"name":"Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6832-6539","authenticated-orcid":false,"given":"Eric","family":"Bouffet","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2112-5251","authenticated-orcid":false,"given":"Ute","family":"Bartels","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Schechter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7883-3710","authenticated-orcid":false,"given":"Tim","family":"Hassall","sequence":"additional","affiliation":[{"name":"Oncology Department, Queensland Children's Hospital and University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Robertson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Royal Brisbane and Women's Hospital, University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Oncology Department, Queensland Children's Hospital and University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0311-7127","authenticated-orcid":false,"given":"Sridharan","family":"Gururangan","sequence":"additional","affiliation":[{"name":"Preston A. 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