% 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{Allguer:305532,
      author       = {M. Allgäuer and K. Kluck and P. Christopoulos and M. Ball
                      and A.-L. Volckmar and T. Radonic and L. Bubendorf and P.
                      Hofman and C. P. Heußel and H. Winter and F. Herth and M.
                      Thomas and B. Ylstra and S. Peters and P. Schirmacher and D.
                      Kazdal$^*$ and J. Budczies$^*$ and A. Stenzinger$^*$ and M.
                      Kirchner},
      title        = {{A}dvancing {L}ung {C}ancer {S}taging: {I}ntegrating
                      {IASLC} {R}ecommendations and {B}ioinformatics to
                      {D}elineate {T}umor {O}rigins.},
      journal      = {Journal of thoracic oncology},
      volume       = {nn},
      issn         = {1556-0864},
      address      = {Amsterdam},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2025-02206},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {Accurate distinction between separate primary lung
                      carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is
                      essential for staging and treatment of multifocal non-small
                      cell lung carcinoma (NSCLC). Next-generation sequencing
                      (NGS) enables assessment of clonal relatedness. The proposed
                      IASLC algorithm integrates histological and molecular data,
                      though its clinical utility is yet to be validated.We
                      focused on the molecular component of the algorithm and
                      assessed 240 tumor pairs from 120 patients with
                      formalin-fixed paraffin-embedded (FFPE) tumor samples that
                      underwent small-scale gene panel NGS testing (31-54 genes)
                      within routine clinical care. Most tumors were
                      adenocarcinomas (n=222), 18 tumors other NSCLC subtypes.
                      Inconclusive pairs by molecular classification were
                      subjected to large-scale panel analyses (531 genes).
                      Additionally, we developed a bioinformatic method to
                      complement and refine the IASLC method.In total 22 tumor
                      pairs $(18\%)$ remained inconclusive and 16 $(13\%)$ were
                      classified ambiguous (probable SPLCs) using the molecular
                      IASLC method. Re-sequencing classified 9 of 22 inconclusive
                      pairs as IPMs. Using a newly developed bioinformatic method
                      for clonality classification incorporating likelihood ratios
                      of mutational prevalence and small-scale sequencing, only 3
                      pairs remained inconclusive $(2\%).$ Tumors classified as
                      SPLCs had a significantly longer overall survival than
                      IPMs.Small-scale panel sequencing of biopsy material allows
                      unambiguous clonality determination in 3 of 4 cases.
                      Large-scale sequencing resolves about half of inconclusive
                      cases. Our bioinformatic method reduces inconclusive pairs
                      to $2\%$ even with small-scale NGS. It is made publicly
                      available as a Shiny App. Clonality is reflected in survival
                      data and therefore pivotal in daily clinical practice.},
      keywords     = {(max. n=5) Multiple pulmonary tumors (Other) / IASLC
                      recommendations (2024) (Other) / Next Generation Sequencing
                      (NGS) (Other) / clonality classification (Other)},
      cin          = {HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)HD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41135642},
      doi          = {10.1016/j.jtho.2025.10.010},
      url          = {https://inrepo02.dkfz.de/record/305532},
}