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@ARTICLE{Mynarek:154606,
      author       = {M. Mynarek and K. von Hoff and T. Pietsch and H.
                      Ottensmeier and M. Warmuth-Metz and B. Bison and S.
                      Pfister$^*$ and A. Korshunov$^*$ and T. Sharma$^*$ and N.
                      Jaeger and M. Ryzhova and O. Zheludkova and A. Golanov and
                      E. J. Rushing and M. Hasselblatt and A. Koch and U.
                      Schüller and A. von Deimling$^*$ and F. Sahm$^*$ and M.
                      Sill$^*$ and M. J. Riemenschneider and H. Dohmen and C. M.
                      Monoranu and C. Sommer and O. Staszewski and C. Mawrin and
                      J. Schittenhelm and W. Brück and K. Filipski$^*$ and C.
                      Hartmann and M. Meinhardt and K. Pietschmann and C. Haberler
                      and I. Slavc and N. U. Gerber and M. Grotzer and M. Benesch
                      and P. G. Schlegel and F. Deinlein and A. O. von Bueren and
                      C. Friedrich and B.-O. Juhnke and D. Obrecht and G.
                      Fleischhack and R. Kwiecien and A. Faldum and R. D. Kortmann
                      and M. Kool$^*$ and S. Rutkowski},
      title        = {{N}onmetastatic {M}edulloblastoma of {E}arly {C}hildhood:
                      {R}esults {F}rom the {P}rospective {C}linical {T}rial
                      {HIT}-2000 and {A}n {E}xtended {V}alidation {C}ohort.},
      journal      = {Journal of clinical oncology},
      volume       = {38},
      number       = {18},
      issn         = {1527-7755},
      address      = {Alexandria, Va.},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2020-00879},
      pages        = {2028-2040},
      year         = {2020},
      note         = {2020 Jun 20;38(18):2028-2040},
      abstract     = {The HIT-2000-BIS4 trial aimed to avoid highly detrimental
                      craniospinal irradiation (CSI) in children < 4 years of age
                      with nonmetastatic medulloblastoma by systemic chemotherapy,
                      intraventricular methotrexate, and risk-adapted local
                      radiotherapy.From 2001-2011, 87 patients received systemic
                      chemotherapy and intraventricular methotrexate. Until 2006,
                      CSI was reserved for nonresponse or progression. After 2006,
                      local radiotherapy was introduced for nonresponders or
                      patients with classic medulloblastoma (CMB) or
                      large-cell/anaplastic medulloblastoma (LCA). DNA methylation
                      profiles of infantile sonic hedgehog-activated
                      medulloblastoma (SHH-INF) were subdivided into iSHH-I and
                      iSHH-II subtypes in the HIT-2000-BIS4 cohort and a
                      validation cohort (n = 71) from the HIT group and
                      Russia.Five years after diagnosis, patients with
                      desmoplastic medulloblastoma (DMB) or medulloblastoma with
                      extensive nodularity (MBEN; n = 42) had $93\%$
                      progression-free survival (5y-PFS), $100\%$ overall survival
                      (5y-OS), and $93\%$ CSI-free (5y-CSI-free) survival.
                      Patients with CMB/LCA (n = 45) had $37\%$ 5y-PFS, $62\%$
                      5y-OS, and $39\%$ 5y-CSI-free survival. Local radiotherapy
                      did not improve survival in patients with CMB/LCA. All
                      DMB/MBEN assessed by DNA methylation profiling belonged to
                      the SHH-INF subgroup. Group 3 patients (5y-PFS, $36\%;$ n =
                      14) relapsed more frequently than the SHH-INF group (5y-PFS,
                      $93\%;$ n = 28) or group 4 patients (5y-PFS, $83\%;$ n = 6;
                      P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in
                      HIT-2000-BIS4 and the validation cohort, without prognostic
                      impact (5y-PFS: iSHH-I, $73\%,$ v iSHH-II, $83\%;$ P = .25;
                      n = 99). Intelligence quotient (IQ) was significantly lower
                      in patients after CSI (mean IQ, 90 [no radiotherapy], v 74
                      [CSI]; P = .012).Systemic chemotherapy and intraventricular
                      methotrexate led to favorable survival in both iSHH subtypes
                      of SHH-activated DMB/MBEN with acceptable neurotoxicity.
                      Survival in patients with non-wingless (WNT)/non-SHH disease
                      with CMB/LCA was not improved by local radiotherapy.
                      Patients with group 4 disease had more favorable survival
                      rates than those with group 3 medulloblastoma.},
      cin          = {B062 / B300 / FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)B300-20160331 /
                      I:(DE-He78)FM01-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32330099},
      doi          = {10.1200/JCO.19.03057},
      url          = {https://inrepo02.dkfz.de/record/154606},
}