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@ARTICLE{Mynarek:124245,
      author       = {M. Mynarek and B. Pizer and C. Dufour and D. van Vuurden
                      and M. Garami and M. Massimino and J. Fangusaro and T.
                      Davidson and M. J. Gil-da-Costa and J. Sterba and M. Benesch
                      and N. Gerber and B. O. Juhnke and R. Kwiecien and T.
                      Pietsch and M. Kool$^*$ and S. Clifford and D. W. Ellison
                      and F. Giangaspero and P. Wesseling and F. Gilles and N.
                      Gottardo and J. L. Finlay and S. Rutkowski and K. von Hoff},
      title        = {{E}valuation of age-dependent treatment strategies for
                      children and young adults with pineoblastoma: analysis of
                      pooled {E}uropean {S}ociety for {P}aediatric {O}ncology
                      ({SIOP}-{E}) and {US} {H}ead {S}tart data.},
      journal      = {Neuro-Oncology},
      volume       = {19},
      number       = {4},
      issn         = {1523-5866},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2017-01141},
      pages        = {576-585},
      year         = {2017},
      abstract     = {Pineoblastoma is a rare pineal region brain tumor.
                      Treatment strategies have reflected those for other
                      malignant embryonal brain tumors.Original prospective
                      treatment and outcome data from international trial groups
                      were pooled. Cox regression models were developed
                      considering treatment elements as time-dependent
                      covariates.Data on 135 patients with pineoblastoma aged
                      0.01-20.7 (median 4.9) years were analyzed. Median
                      observation time was 7.3 years. Favorable prognostic factors
                      were age ≥4 years (hazard ratio [HR] for progression-free
                      survival [PFS] 0.270, P < .001) and administration of
                      radiotherapy (HR for PFS 0.282, P < .001). Metastatic
                      disease (HR for PFS 2.015, P = .006), but not postoperative
                      residual tumor, was associated with unfavorable prognosis.
                      In 57 patients <4 years old, 5-year PFS/overall survival
                      (OS) were 11 ± $4\%/12$ ± $4\%.$ Two patients survived
                      after chemotherapy only, while 3 of 16 treated with
                      craniospinal irradiation (CSI) with boost, and 3 of 5
                      treated with high-dose chemotherapy (HDCT) and local
                      radiotherapy survived. In 78 patients aged ≥4 years,
                      PFS/OS were 72 ± $7\%/73$ ± $7\%$ for patients without
                      metastases, and 50 ± $10\%/55$ ± $10\%$ with metastases.
                      Seventy-three patients received radiotherapy (48
                      conventionally fractionated CSI, median dose 35.0
                      [18.0-45.0] Gy, 19 hyperfractionated CSI, 6 local
                      radiotherapy), with (n = 68) or without (n = 6)
                      chemotherapy. The treatment sequence had no impact;
                      application of HDCT had weak impact on survival in older
                      patients.Survival is poor in young children treated without
                      radiotherapy. In these patients, combination of HDCT and
                      local radiotherapy may warrant further evaluation in the
                      absence of more specific or targeted treatments. CSI
                      combined with chemotherapy is effective for older
                      non-metastatic patients.},
      cin          = {B062},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28011926},
      pmc          = {pmc:PMC5464312},
      doi          = {10.1093/neuonc/now234},
      url          = {https://inrepo02.dkfz.de/record/124245},
}