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@ARTICLE{Worst:130973,
      author       = {B. Worst$^*$ and C. M. van Tilburg$^*$ and G. P.
                      Balasubramanian$^*$ and P. Fiesel$^*$ and R. Witt and A.
                      Freitag and M. Boudalil$^*$ and C. Previti$^*$ and S.
                      Wolf$^*$ and S. Schmidt$^*$ and S. Chotewutmontri$^*$ and M.
                      Bewerunge-Hudler$^*$ and M. Schick$^*$ and M. Schlesner$^*$
                      and B. Hutter$^*$ and L. Taylor and T. Borst and C. Sutter
                      and C. R. Bartram and T. Milde$^*$ and E. Pfaff$^*$ and A.
                      E. Kulozik and A. von Stackelberg and R. Meisel and A.
                      Borkhardt and D. Reinhardt and J.-H. Klusmann and G.
                      Fleischhack and S. Tippelt and U. Dirksen and H. Jürgens
                      and C. M. Kramm and A. O. von Bueren and F. Westermann$^*$
                      and M. Fischer and B. Burkhardt and W. Wößmann and M.
                      Nathrath and S. S. Bielack and M. C. Frühwald and S.
                      Fulda$^*$ and T. Klingebiel and E. Koscielniak and M.
                      Schwab$^*$ and R. Tremmel and P. H. Driever and J. H.
                      Schulte and B. Brors$^*$ and A. von Deimling$^*$ and P.
                      Lichter$^*$ and A. Eggert and D. Capper$^*$ and S.
                      Pfister$^*$ and D. Jones$^*$ and O. Witt$^*$},
      title        = {{N}ext-generation personalised medicine for high-risk
                      paediatric cancer patients - {T}he {INFORM} pilot study.},
      journal      = {European journal of cancer},
      volume       = {65},
      issn         = {0959-8049},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2017-06049},
      pages        = {91 - 101},
      year         = {2016},
      abstract     = {The Individualized Therapy for Relapsed Malignancies in
                      Childhood (INFORM) precision medicine study is a nationwide
                      German program for children with high-risk
                      relapsed/refractory malignancies, which aims to identify
                      therapeutic targets on an individualised basis. In a pilot
                      phase, reported here, we developed the logistical and
                      analytical pipelines necessary for rapid and comprehensive
                      molecular profiling in a clinical setting. Fifty-seven
                      patients from 20 centers were prospectively recruited.
                      Malignancies investigated included sarcomas (n = 25),
                      brain tumours (n = 23), and others (n = 9). Whole-exome,
                      low-coverage whole-genome, and RNA sequencing were
                      complemented with methylation and expression microarray
                      analyses. Alterations were assessed for potential
                      targetability according to a customised prioritisation
                      algorithm and subsequently discussed in an interdisciplinary
                      molecular tumour board. Next-generation sequencing data were
                      generated for 52 patients, with the full analysis possible
                      in 46 of 52. Turnaround time from sample receipt until first
                      report averaged 28 d. Twenty-six patients $(50\%)$ harbored
                      a potentially druggable alteration with a prioritisation
                      score of intermediate or higher (level 4 of 7). Common
                      targets included receptor tyrosine kinases, phosphoinositide
                      3-kinase-mammalian target of rapamycin pathway,
                      mitogen-activated protein kinase pathway, and cell cycle
                      control. Ten patients received a targeted therapy based on
                      these findings, with responses observed in some previously
                      treatment-refractory tumours. Comparative primary relapse
                      analysis revealed substantial tumour evolution as well as
                      one case of unsuspected secondary malignancy, highlighting
                      the importance of re-biopsy at relapse. This study
                      demonstrates the feasibility of comprehensive, real-time
                      molecular profiling for high-risk paediatric cancer
                      patients. This extended proof-of-concept, with examples of
                      treatment consequences, expands upon previous personalised
                      oncology endeavors, and presents a model with considerable
                      interest and practical relevance in the burgeoning era of
                      personalised medicine.},
      cin          = {B062 / G040 / G200 / G380 / B080 / G340 / B087 / W110 /
                      B060 / L101 / L501 / L201 / L401},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)G040-20160331 /
                      I:(DE-He78)G200-20160331 / I:(DE-He78)G380-20160331 /
                      I:(DE-He78)B080-20160331 / I:(DE-He78)G340-20160331 /
                      I:(DE-He78)B087-20160331 / I:(DE-He78)W110-20160331 /
                      I:(DE-He78)B060-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)L501-20160331 / I:(DE-He78)L201-20160331 /
                      I:(DE-He78)L401-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:27479119},
      doi          = {10.1016/j.ejca.2016.06.009},
      url          = {https://inrepo02.dkfz.de/record/130973},
}