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@ARTICLE{Juhnke:168539,
      author       = {B.-O. Juhnke and M. Gessi and N. U. Gerber and C. Friedrich
                      and M. Mynarek and A. O. von Bueren and C. Haberler and U.
                      Schüller and R.-D. Kortmann and B. Timmermann$^*$ and B.
                      Bison and M. Warmuth-Metz and R. Kwiecien and S. M.
                      Pfister$^*$ and C. Spix and T. Pietsch and M. Kool$^*$ and
                      S. Rutkowski and K. von Hoff},
      title        = {{T}reatment of {E}mbryonal {T}umours with {M}ultilayered
                      {R}osettes with {C}arboplatin/{E}toposide {I}nduction and
                      {H}igh-dose {C}hemotherapy within the {P}rospective
                      {P}-{HIT} {T}rial.},
      journal      = {Neuro-Oncology},
      volume       = {24},
      number       = {1},
      issn         = {1523-5866},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2021-00965},
      pages        = {127-137},
      year         = {2022},
      note         = {2022 Jan 5;24(1):127-137},
      abstract     = {Embryonal tumours with multilayered rosettes (ETMR) are
                      highly aggressive tumours occurring in early childhood.
                      Published clinical data refer to retrospective,
                      heterogeneously treated cohorts. Here, we describe the
                      outcome of patients treated according to the prospective
                      P-HIT trial and subsequent
                      HIT2000-interim-registry.Age-stratified treatment included
                      carboplatin/etoposide-induction, tandem-high-dose
                      chemotherapy ('CARBO/ETO+HDCT') and response-stratified
                      radiotherapy. Patients with centrally reviewed
                      neuropathological and molecularly confirmed diagnosis of
                      ETMR recruited within the P-HIT trial (2001-2011; n=19), the
                      HIT2000-interim-registry (2012-2014; n=12) and earlier
                      HIT-trials (n=4) were selected for analysis.Age-adjusted
                      incidence rate was 1.35 per 1 million children (aged 1-4
                      years) in the years 2012-2014. Median age at diagnosis for
                      35 patients was 2.9 years. Metastases at diagnosis were
                      detected in 9 patients. One patient died due to
                      postoperative complications. For 30 patients with
                      non-brainstem tumour location, 5-year progression-free (PFS)
                      and overall survival (OS) were $35\%$ and $47\%$ after
                      treatment with CARBO/ETO+HDCT (n=17), compared to $0\%$ and
                      $8\%$ with other treatments (n=13, p[OS]=0.011). All 4
                      patients with brainstem tumour died within 10 months after
                      diagnosis. By multivariable analysis, supratentorial
                      location: (HR[PFS]:0.07 $[95\%CI:0.01-0.38],$ p=0.003),
                      localised disease (M0): (HR[OS] M0, no residual tumor:0.30
                      $[95\%CI:0.009-1.09],$ p=0.068; M0, residual tumor:0.18
                      $[95\%CI:$ 0.04-0.76], p=0.020) and CARBO/ETO+HDCT treatment
                      (HR[OS]:0.16 $[95\%CI:0.05-054],$ p=0.003) were identified
                      as independent prognostic factors. Of 9 survivors, 6 were
                      treated with radiotherapy (craniospinal 4; local 2).Our data
                      indicate improved survival with intensified chemotherapy
                      (CARBO/ETO+HDCT). However, despite intensive treatment, the
                      outcome was poor. Thus, innovative therapies need to be
                      evaluated urgently in an upfront setting.},
      keywords     = {ETMR (Other) / clinical trial (Other) / high-dose
                      chemotherapy (Other) / incidence (Other) / outcome (Other)},
      cin          = {ED01 / HD01 / B062},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B062-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33908610},
      doi          = {10.1093/neuonc/noab100},
      url          = {https://inrepo02.dkfz.de/record/168539},
}