% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Gajjar:166689, author = {A. Gajjar and G. W. Robinson and K. S. Smith and T. Lin and T. E. Merchant and M. Chintagumpala and A. Mahajan and J. Su and E. Bouffet and U. Bartels and T. Schechter and T. Hassall and T. Robertson and W. Nicholls and S. Gururangan and K. Schroeder and M. Sullivan and G. Wheeler and J. R. Hansford and S. J. Kellie and G. McCowage and R. Cohn and M. J. Fisher and M. J. Krasin and C. F. Stewart and A. Broniscer and I. Buchhalter$^*$ and R. G. Tatevossian and B. A. Orr and G. Neale and P. Klimo and F. Boop and A. Srinivasan and S. M. Pfister$^*$ and R. J. Gilbertson and A. Onar-Thomas and D. W. Ellison and P. A. Northcott}, title = {{O}utcomes by {C}linical and {M}olecular {F}eatures in {C}hildren {W}ith {M}edulloblastoma {T}reated {W}ith {R}isk-{A}dapted {T}herapy: {R}esults of an {I}nternational {P}hase {III} {T}rial ({SJMB}03).}, journal = {Journal of clinical oncology}, volume = {39}, number = {7}, issn = {1527-7755}, address = {Alexandria, Va.}, publisher = {American Society of Clinical Oncology}, reportid = {DKFZ-2021-00042}, pages = {822-835}, year = {2021}, note = {2021 Mar 1;39(7):822-835}, abstract = {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.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.}, cin = {W610 / B062 / HD01}, ddc = {610}, cid = {I:(DE-He78)W610-20160331 / I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331}, pnm = {312 - Funktionelle und strukturelle Genomforschung (POF4-312)}, pid = {G:(DE-HGF)POF4-312}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:33405951}, doi = {10.1200/JCO.20.01372}, url = {https://inrepo02.dkfz.de/record/166689}, }