000166689 001__ 166689 000166689 005__ 20240229133527.0 000166689 0247_ $$2doi$$a10.1200/JCO.20.01372 000166689 0247_ $$2pmid$$apmid:33405951 000166689 0247_ $$2ISSN$$a0732-183X 000166689 0247_ $$2ISSN$$a1527-7755 000166689 0247_ $$2altmetric$$aaltmetric:97263171 000166689 037__ $$aDKFZ-2021-00042 000166689 041__ $$aeng 000166689 082__ $$a610 000166689 1001_ $$aGajjar, Amar$$b0 000166689 245__ $$aOutcomes by Clinical and Molecular Features in Children With Medulloblastoma Treated With Risk-Adapted Therapy: Results of an International Phase III Trial (SJMB03). 000166689 260__ $$aAlexandria, Va.$$bAmerican Society of Clinical Oncology$$c2021 000166689 3367_ $$2DRIVER$$aarticle 000166689 3367_ $$2DataCite$$aOutput Types/Journal article 000166689 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1615295137_26330 000166689 3367_ $$2BibTeX$$aARTICLE 000166689 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000166689 3367_ $$00$$2EndNote$$aJournal Article 000166689 500__ $$a2021 Mar 1;39(7):822-835 000166689 520__ $$aSJMB03 (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.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.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 > 90%) and two very high-risk groups (high-risk SHH and high-risk combined groups 3 and 4) with poor survival (5-year PFS < 60%).These results establish a new risk stratification for future medulloblastoma trials. 000166689 536__ $$0G:(DE-HGF)POF4-312$$a312 - Funktionelle und strukturelle Genomforschung (POF4-312)$$cPOF4-312$$fPOF IV$$x0 000166689 588__ $$aDataset connected to CrossRef, PubMed, 000166689 7001_ $$aRobinson, Giles W$$b1 000166689 7001_ $$aSmith, Kyle S$$b2 000166689 7001_ $$aLin, Tong$$b3 000166689 7001_ $$aMerchant, Thomas E$$b4 000166689 7001_ $$aChintagumpala, Murali$$b5 000166689 7001_ $$aMahajan, Anita$$b6 000166689 7001_ $$aSu, Jack$$b7 000166689 7001_ $$aBouffet, Eric$$b8 000166689 7001_ $$aBartels, Ute$$b9 000166689 7001_ $$aSchechter, Tal$$b10 000166689 7001_ $$aHassall, Tim$$b11 000166689 7001_ $$aRobertson, Thomas$$b12 000166689 7001_ $$aNicholls, Wayne$$b13 000166689 7001_ $$aGururangan, Sridharan$$b14 000166689 7001_ $$aSchroeder, Kristin$$b15 000166689 7001_ $$aSullivan, Michael$$b16 000166689 7001_ $$aWheeler, Greg$$b17 000166689 7001_ $$aHansford, Jordan R$$b18 000166689 7001_ $$aKellie, Stewart J$$b19 000166689 7001_ $$aMcCowage, Geoffrey$$b20 000166689 7001_ $$aCohn, Richard$$b21 000166689 7001_ $$aFisher, Michael J$$b22 000166689 7001_ $$aKrasin, Matthew J$$b23 000166689 7001_ $$aStewart, Clinton F$$b24 000166689 7001_ $$aBroniscer, Alberto$$b25 000166689 7001_ $$0P:(DE-He78)e84b3187ddd3529f884082e30f228c66$$aBuchhalter, Ivo$$b26$$udkfz 000166689 7001_ $$aTatevossian, Ruth G$$b27 000166689 7001_ $$aOrr, Brent A$$b28 000166689 7001_ $$aNeale, Geoff$$b29 000166689 7001_ $$aKlimo, Paul$$b30 000166689 7001_ $$aBoop, Frederick$$b31 000166689 7001_ $$aSrinivasan, Ashok$$b32 000166689 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b33$$udkfz 000166689 7001_ $$aGilbertson, Richard J$$b34 000166689 7001_ $$aOnar-Thomas, Arzu$$b35 000166689 7001_ $$aEllison, David W$$b36 000166689 7001_ $$aNorthcott, Paul A$$b37 000166689 773__ $$0PERI:(DE-600)2005181-5$$a10.1200/JCO.20.01372$$gp. 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