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@ARTICLE{Andreiuolo:131487,
      author       = {F. Andreiuolo and G. Le Teuff and M. A. Bayar and J.-P.
                      Kilday and T. Pietsch and A. O. von Bueren and H. Witt$^*$
                      and A. Korshunov$^*$ and P. Modena and S. Pfister$^*$ and M.
                      Pagès and D. Castel and F. Giangaspero and L. Chimelli and
                      P. Varlet and S. Rutkowski and D. Frappaz and M. Massimino
                      and R. Grundy and J. Grill},
      collaboration = {S. E. B. W. G. BIOMECA},
      title        = {{I}ntegrating {T}enascin-{C} protein expression and 1q25
                      copy number status in pediatric intracranial ependymoma
                      prognostication: {A} new model for risk stratification.},
      journal      = {PLoS one},
      volume       = {12},
      number       = {6},
      issn         = {1932-6203},
      address      = {Lawrence, Kan.},
      publisher    = {PLoS},
      reportid     = {DKFZ-2017-06154},
      pages        = {e0178351 -},
      year         = {2017},
      abstract     = {Despite multimodal therapy, prognosis of pediatric
                      intracranial ependymomas remains poor with a 5-year survival
                      rate below $70\%$ and frequent late deaths.This multicentric
                      European study evaluated putative prognostic biomarkers.
                      Tenascin-C (TNC) immunohistochemical expression and copy
                      number status of 1q25 were retained for a pooled analysis of
                      5 independent cohorts. The prognostic value of TNC and 1q25
                      on the overall survival (OS) was assessed using a Cox model
                      adjusted to age at diagnosis, tumor location, WHO grade,
                      extent of resection, radiotherapy and stratified by cohort.
                      Stratification on a predictor that did not satisfy the
                      proportional hazards assumption was considered. Model
                      performance was evaluated and an internal-external cross
                      validation was performed.Among complete cases with 5-year
                      median follow-up (n = 470; 131 deaths), TNC and 1q25 gain
                      were significantly associated with age at diagnosis and
                      posterior fossa tumor location. 1q25 status added
                      independent prognostic value for death beyond the classical
                      variables with a hazard ratio (HR) = 2.19 $95\%CI$ = [1.29;
                      3.76] (p = 0.004), while TNC prognostic relation was tumor
                      location-dependent with HR = 2.19 $95\%CI$ = [1.29; 3.76] (p
                      = 0.004) in posterior fossa and HR = 0.64 [0.28; 1.48] (p =
                      0.295) in supratentorial (interaction p value = 0.015). The
                      derived prognostic score identified 3 different robust risk
                      groups. The omission of upfront RT was not associated with
                      OS for good and intermediate prognostic groups while the
                      absence of upfront RT was negatively associated with OS in
                      the poor risk group.Integrated TNC expression and 1q25
                      status are useful to better stratify patients and to
                      eventually adapt treatment regimens in pediatric
                      intracranial ependymoma.},
      keywords     = {Tenascin (NLM Chemicals)},
      cin          = {B062 / G380},
      ddc          = {500},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)G380-20160331},
      pnm          = {319H - Addenda (POF3-319H)},
      pid          = {G:(DE-HGF)POF3-319H},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28617804},
      pmc          = {pmc:PMC5472261},
      doi          = {10.1371/journal.pone.0178351},
      url          = {https://inrepo02.dkfz.de/record/131487},
}