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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
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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.
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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
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