% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Langenberg:181934,
      author       = {K. P. S. Langenberg and M. T. Meister and J. J. Bakhuizen
                      and J. M. Boer and N. K. A. van Eijkelenburg and E. Hulleman
                      and U. Ilan and E. J. Looze and M. P. Dierselhuis and J. van
                      der Lugt and W. Breunis and L. G. Schild and K. Ober and S.
                      R. van Hooff and M. A. Scheijde-Vermeulen and L. S.
                      Hiemcke-Jiwa and U. E. Flucke and M. E. G. Kranendonk and P.
                      Wesseling and E. Sonneveld and S. Punt and A. Boltjes and F.
                      van Dijk and E. T. P. Verwiel and R. Volckmann and J. Y.
                      Hehir-Kwa and L. A. Kester and M. M. J. Koudijs and E.
                      Waanders and F. C. P. Holstege and H. J. Vormoor and E. W.
                      Hoving and M. M. van Noesel and R. Pieters and M. Kool$^*$
                      and M. Stumpf and M. Blattner-Johnson$^*$ and G. P.
                      Balasubramanian$^*$ and C. M. Van Tilburg$^*$ and B. C.
                      Jones$^*$ and D. T. W. Jones$^*$ and O. Witt$^*$ and S. M.
                      Pfister$^*$ and M. C. J. Jongmans and R. P. Kuiper and R. R.
                      de Krijger and M. H. W. Wijnen and M. L. den Boer and C. M.
                      Zwaan and P. Kemmeren and J. Koster and B. B. J. Tops and B.
                      F. Goemans and J. J. Molenaar},
      title        = {{I}mplementation of paediatric precision oncology into
                      clinical practice: {T}he {I}ndividualized {T}herapies for
                      {C}hildren with cancer program 'i{THER}'.},
      journal      = {European journal of cancer},
      volume       = {175},
      issn         = {0014-2964},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2022-02304},
      pages        = {311 - 325},
      year         = {2022},
      abstract     = {iTHER is a Dutch prospective national precision oncology
                      program aiming to define tumour molecular profiles in
                      children and adolescents with primary very high-risk,
                      relapsed, or refractory paediatric tumours. Between April
                      2017 and April 2021, 302 samples from 253 patients were
                      included. Comprehensive molecular profiling including
                      low-coverage whole genome sequencing (lcWGS), whole exome
                      sequencing (WES), RNA sequencing (RNA-seq), Affymetrix,
                      and/or 850k methylation profiling was successfully performed
                      for 226 samples with at least $20\%$ tumour content.
                      Germline pathogenic variants were identified in $16\%$ of
                      patients (35/219), of which 22 variants were judged
                      causative for a cancer predisposition syndrome. At least one
                      somatic alteration was detected in 204 $(90.3\%),$ and 185
                      $(81.9\%)$ were considered druggable, with clinical priority
                      very high $(6.1\%),$ high $(21.3\%),$ moderate $(26.0\%),$
                      intermediate $(36.1\%),$ and borderline $(10.5\%)$ priority.
                      iTHER led to revision or refinement of diagnosis in 8
                      patients $(3.5\%).$ Temporal heterogeneity was observed in
                      paired samples of 15 patients, indicating the value of
                      sequential analyses. Of 137 patients with follow-up beyond
                      twelve months, 21 molecularly matched treatments were
                      applied in 19 patients $(13.9\%),$ with clinical benefit in
                      few. Most relevant barriers to not applying targeted
                      therapies included poor performance status, as well as
                      limited access to drugs within clinical trial. iTHER
                      demonstrates the feasibility of comprehensive molecular
                      profiling across all ages, tumour types and stages in
                      paediatric cancers, informing of diagnostic, prognostic, and
                      targetable alterations as well as reportable germline
                      variants. Therefore, WES and RNA-seq is nowadays standard
                      clinical care at the Princess Máxima Center for all
                      children with cancer, including patients at primary
                      diagnosis. Improved access to innovative treatments within
                      biology-driven combination trials is required to ultimately
                      improve survival.},
      keywords     = {Adolescent (Other) / Cancer (Other) / Child (Other) /
                      Hereditary (Other) / Molecular biology (Other) / Molecular
                      targeted therapy (Other) / Next-generation sequencing
                      (Other) / Precision medicine (Other)},
      cin          = {B062 / HD01 / B360 / B310},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B360-20160331 / I:(DE-He78)B310-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36182817},
      doi          = {10.1016/j.ejca.2022.09.001},
      url          = {https://inrepo02.dkfz.de/record/181934},
}