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@ARTICLE{Angeles:275755,
      author       = {A. Angeles$^*$ and F. Janke$^*$ and A.-K. Daum$^*$ and M.
                      Reck and M. A. Schneider and M. Thomas and P. Christopoulos
                      and H. Sültmann$^*$},
      title        = {{I}ntegrated circulating tumour {DNA} and cytokine analysis
                      for therapy monitoring of {ALK}-rearranged lung
                      adenocarcinoma.},
      journal      = {British journal of cancer},
      volume       = {129},
      number       = {1},
      issn         = {0007-0920},
      address      = {Edinburgh},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2023-00854},
      pages        = {112-121},
      year         = {2023},
      note         = {#EA:B063#LA:B063# / 2023 Jul;129(1):112-121},
      abstract     = {Detection of circulating tumour DNA (ctDNA) in biological
                      fluids is a minimally invasive alternative to tissue biopsy
                      for therapy monitoring. Cytokines are released in the tumour
                      microenvironment to influence inflammation and tumorigenic
                      mechanisms. Here, we investigated the potential biomarker
                      utility of circulating cytokines vis-à-vis ctDNA in
                      ALK-rearranged+ lung adenocarcinoma (ALK + NSCLC) and
                      explored the optimal combination of molecular parameters
                      that could indicate disease progression.Longitudinal serum
                      samples (n = 296) were collected from ALK + NSCLC patients
                      (n = 38) under tyrosine kinase inhibitor (TKI) therapy and
                      assayed to quantify eight cytokines: IFN-γ, IL-1β, IL-6,
                      IL-8, IL-10, IL-12p70, MCP1 and TNF-α. Generalised linear
                      mixed-effect modelling was performed to test the performance
                      of different combinations of cytokines and previously
                      determined ctDNA parameters in identifying progressive
                      disease.Serum IL-6, IL-8 and IL-10 were elevated at
                      progressive disease, with IL-8 having the most significant
                      impact as a biomarker. Integrating changes in IL-8 with
                      ctDNA parameters maximised the performance of the
                      classifiers in identifying disease progression, but this did
                      not significantly outperform the model based on ctDNA
                      alone.Serum cytokine levels are potential disease
                      progression markers in ALK + NSCLC. Further validation in a
                      larger and prospective cohort is necessary to determine
                      whether the addition of cytokine evaluation could improve
                      current tumour monitoring modalities in the clinical
                      setting.},
      cin          = {B063 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B063-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37120670},
      doi          = {10.1038/s41416-023-02284-0},
      url          = {https://inrepo02.dkfz.de/record/275755},
}