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@ARTICLE{vonBueren:130736,
      author       = {A. O. von Bueren and R.-D. Kortmann and K. von Hoff and C.
                      Friedrich and M. Mynarek and K. Müller and T. Goschzik and
                      A. Zur Mühlen and N. Gerber and M. Warmuth-Metz and N.
                      Soerensen and F. Deinlein and M. Benesch and I. Zwiener and
                      R. Kwiecien and A. Faldum and U. Bode and G. Fleischhack and
                      V. Hovestadt$^*$ and M. Kool$^*$ and D. Jones$^*$ and P.
                      Northcott$^*$ and J. Kuehl and S. Pfister$^*$ and T. Pietsch
                      and S. Rutkowski},
      title        = {{T}reatment of {C}hildren and {A}dolescents {W}ith
                      {M}etastatic {M}edulloblastoma and {P}rognostic {R}elevance
                      of {C}linical and {B}iologic {P}arameters.},
      journal      = {Journal of clinical oncology},
      volume       = {34},
      number       = {34},
      issn         = {1527-7755},
      address      = {Alexandria, Va.},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2017-05814},
      pages        = {4151 - 4160},
      year         = {2016},
      abstract     = {Purpose To assess an intensified treatment in the context
                      of clinical and biologic risk factors in metastatic
                      medulloblastoma. Patients and Methods Patients (4 to 21
                      years old, diagnosed between 2001 and 2007) received
                      induction chemotherapy, dose-escalated hyperfractionated
                      craniospinal radiotherapy, and maintenance chemotherapy.
                      Subgroup status and other biologic parameters were assessed.
                      Results In 123 eligible patients (median age, 8.2 years old;
                      median follow-up, 5.38 years), 5-year event-free survival
                      (EFS) and overall survival (OS) were $62\%$ $(95\%$ CI, 52
                      to 72) and $74\%$ $(95\%$ CI, 66 to 82), respectively. OS
                      was superior compared with the precedent HIT '91 trial. The
                      5-year EFS and OS were both $89\%$ $(95\%$ CI, 67 to 100)
                      for desmoplastic/nodular (n = 11), $61\%$ $(95\%$ CI, 51 to
                      71) and $75\%$ $(95\%$ CI, 65 to 85) for classic (n = 107),
                      and $20\%$ $(95\%$ CI, 0 to 55) and $40\%$ $(95\%$ CI, 0 to
                      83) for large-cell/anaplastic (n = 5) medulloblastoma ( P <
                      .001 for EFS; P = .001 for OS). Histology (hazard ratio,
                      0.19 for desmoplastic/nodular and 45.97 for
                      large-cell/anaplastic medulloblastoma) and nonresponse to
                      the first chemotherapy cycle (hazard ratio, 1.97) were
                      independent risk factors (EFS). Among 81 $(66\%)$ patients
                      with tumor material, 5-year EFS and OS differed between
                      low-risk (wingless [WNT], n = 4; both $100\%),$ high-risk (
                      MYCC/ MYCN amplification; n = 5, both $20\%),$ and
                      intermediate-risk patients (neither; n = 72, $63\%$ and
                      $73\%,$ respectively). Survival rates were different between
                      molecular subgroups (WNT, n = 4; sonic hedgehog [SHH; n =
                      4]; group 4 [n = 41]; group 3 with [n = 3] or without [n =
                      17] MYCC/MYCN amplification; P < .001). All cases showed p53
                      immuno-negativity. There was no association between patients
                      with nonresponding tumors to induction chemotherapy and WNT
                      ( P = .143) or MYCC/MYCN status ( P = .075), histologic
                      subtype ( P = .814), or molecular subtype ( P = .383), as
                      assessed by Fisher's exact test. Conclusion This regimen was
                      feasible and conferred overall favorable survival. Our data
                      confirm the relevance of subgroup status and biologic
                      parameters (WNT/ MYCC/ MYCN status) in a homogeneous
                      prospective trial population, and show that metastatic group
                      3 patients do not uniformly have poor outcomes. Biologic
                      subgroup, MYCC/ MYCN status, response to induction
                      chemotherapy, and histologic subtype may serve for improved
                      treatment stratification.},
      cin          = {B060 / B062 / L101},
      ddc          = {050},
      cid          = {I:(DE-He78)B060-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)L101-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:27863192},
      doi          = {10.1200/JCO.2016.67.2428},
      url          = {https://inrepo02.dkfz.de/record/130736},
}