% 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{Thierauf:143287,
      author       = {J. Thierauf and N. Ramamurthy and V. Y. Jo and H. Robinson
                      and R. P. Frazier and J. Gonzalez and M. Pacula and E.
                      Dominguez Meneses and V. Nose and V. Nardi and D.
                      Dias-Santagata and L. P. Le and D. T. Lin and W. C. Faquin
                      and L. J. Wirth and J. Hess$^*$ and A. J. Iafrate and J. K.
                      Lennerz},
      title        = {{C}linically {I}ntegrated {M}olecular {D}iagnostics in
                      {A}denoid {C}ystic {C}arcinoma.},
      journal      = {The oncologist},
      volume       = {24},
      number       = {10},
      issn         = {1549-490X},
      address      = {Hoboken, NJ},
      publisher    = {Wiley},
      reportid     = {DKFZ-2019-00885},
      pages        = {1356-1367},
      year         = {2019},
      abstract     = {Adenoid cystic carcinoma (ACC) is an aggressive salivary
                      gland malignancy without effective systemic therapies.
                      Delineation of molecular profiles in ACC has led to an
                      increased number of biomarker-stratified clinical trials;
                      however, the clinical utility and U.S.-centric financial
                      sustainability of integrated next-generation sequencing
                      (NGS) in routine practice has, to our knowledge, not been
                      assessed.In our practice, NGS genotyping was implemented at
                      the discretion of the primary clinician. We combined
                      NGS-based mutation and fusion detection, with MYB
                      break-apart fluorescent in situ hybridization (FISH) and MYB
                      immunohistochemistry. Utility was defined as the fraction of
                      patients with tumors harboring alterations that are
                      potentially amenable to targeted therapies. Financial
                      sustainability was assessed using the fraction of global
                      reimbursement.Among 181 consecutive ACC cases (2011-2018),
                      prospective genotyping was performed in $11\%$ (n = 20/181;
                      n = 8 nonresectable). Testing identified 5/20 $(25\%)$
                      NOTCH1 aberrations, 6/20 $(30\%)$ MYB-NFIB fusions (all
                      confirmed by FISH), and 2/20 $(10\%)$ MYBL1-NFIB fusions.
                      Overall, these three alterations (MYB/MYBL1/NOTCH1) made up
                      $65\%$ of patients, and this subset had a more aggressive
                      course with significantly shorter progression-free survival.
                      In $75\%$ (n = 6/8) of nonresectable patients, we detected
                      potentially actionable alterations. Financial analysis of
                      the global charges, including NGS codes, indicated $63\%$
                      reimbursement, which is in line with national (U.S.-based)
                      and international levels of reimbursement CONCLUSION:
                      Prospective routine clinical genotyping in ACC can identify
                      clinically relevant subsets of patients and is approaching
                      financial sustainability. Demonstrating clinical utility and
                      financial sustainability in an orphan disease (ACC) requires
                      a multiyear and multidimensional program.Delineation of
                      molecular profiles in adenoid cystic carcinoma (ACC) has
                      been accomplished in the research setting; however, the
                      ability to identify relevant patient subsets in clinical
                      practice has not been assessed. This work presents an
                      approach to perform integrated molecular genotyping of
                      patients with ACC with nonresectable, recurrent, or systemic
                      disease. It was determined that $75\%$ of nonresectable
                      patients harbor potentially actionable alterations and that
                      $63\%$ of charges are reimbursed. This report outlines that
                      orphan diseases such as ACC require a multiyear,
                      multidimensional program to demonstrate utility in clinical
                      practice.},
      cin          = {A102},
      ddc          = {610},
      cid          = {I:(DE-He78)A102-20160331},
      pnm          = {311 - Signalling pathways, cell and tumor biology
                      (POF3-311)},
      pid          = {G:(DE-HGF)POF3-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30926674},
      doi          = {10.1634/theoncologist.2018-0515},
      url          = {https://inrepo02.dkfz.de/record/143287},
}