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@ARTICLE{Placke:282517,
      author       = {J.-M. Placke$^*$ and M. Kimmig and K. Griewank and R.
                      Herbst and P. Terheyden and J. Utikal$^*$ and C. Pföhler
                      and J. Ulrich and A. Kreuter and P. Mohr and R. Gutzmer and
                      F. Meier and E. Dippel and J. Welzel and D. R. Engel$^*$ and
                      S. Kreft and A. Sucker and G. Lodde and F. Krefting and I.
                      Stoffels and J. Klode and A. Roesch$^*$ and L. Zimmer and E.
                      Livingstone and E. Hadaschik and J. Becker$^*$ and M.
                      Weichenthal and A. Tasdogan$^*$ and D. Schadendorf$^*$ and
                      S. Ugurel$^*$},
      title        = {{C}orrelation of tumor {PD}-{L}1 expression in different
                      tissue types and outcome of {PD}-1-based immunotherapy in
                      metastatic melanoma - analysis of the {D}e{COG} prospective
                      multicenter cohort study {ADOREG}/{TRIM}.},
      journal      = {EBioMedicine},
      volume       = {96},
      issn         = {2352-3964},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2023-01806},
      pages        = {104774},
      year         = {2023},
      abstract     = {PD-1-based immune checkpoint inhibition (ICI) is the major
                      backbone of current melanoma therapy. Tumor PD-L1 expression
                      represents one of few biomarkers predicting ICI therapy
                      outcome. The objective of the present study was to
                      systematically investigate whether the type of tumor tissue
                      examined for PD-L1 expression has an impact on the
                      correlation with ICI therapy outcome.Pre-treatment tumor
                      tissue was collected within the prospective DeCOG cohort
                      study ADOREG/TRIM (CA209-578; NCT05750511) between February
                      2014 and May 2020 from 448 consecutive patients who received
                      PD-1-based ICI for non-resectable metastatic melanoma. The
                      primary study endpoint was best overall response (BOR),
                      secondary endpoints were progression-free (PFS) and overall
                      survival (OS). All endpoints were correlated with tumor
                      PD-L1 expression (quantified with clone 28-8; cutoff
                      $≥5\%)$ and stratified by tissue type.Tumor PD-L1 was
                      determined in 95 primary tumors (PT; $36.8\%$ positivity),
                      153 skin/subcutaneous $(34.0\%$ positivity), 115 lymph node
                      (LN; $50.4\%$ positivity), and 85 organ $(40.8\%$
                      positivity) metastases. Tumor PD-L1 correlated with BOR if
                      determined in LN (OR = 0.319; $95\%$ CI = 0.138-0.762; P =
                      0.010), but not in skin/subcutaneous metastases (OR = 0.656;
                      $95\%$ CI = 0.311-1.341; P = 0.26). PD-L1 positivity
                      determined on LN metastases was associated with favorable
                      survival (PFS, HR = 0.490; $95\%$ CI = 0.310-0.775; P =
                      0.002; OS, HR = 0.519; $95\%$ CI = 0.307-0.880; P = 0.014).
                      PD-L1 positivity determined in PT (PFS, HR = 0.757; $95\%$
                      CI = 0.467-1.226; P = 0.27; OS; HR = 0.528; $95\%$ CI =
                      0.305-0.913; P = 0.032) was correlated with survival to a
                      lesser extent. No relevant survival differences were
                      detected by PD-L1 determined in skin/subcutaneous metastases
                      (PFS, HR = 0.825; $95\%$ CI = 0.555-1.226; P = 0.35; OS, HR
                      = 1.083; $95\%$ CI = 0.698-1.681; P = 0.72).For PD-1-based
                      immunotherapy in melanoma, tumor PD-L1 determined in LN
                      metastases was stronger correlated with therapy outcome than
                      that assessed in PT or organ metastases. PD-L1 determined in
                      skin/subcutaneous metastases showed no outcome correlation
                      and therefore should be used with caution for clinical
                      decision making.Bristol-Myers Squibb (ADOREG/TRIM,
                      NCT05750511); German Research Foundation (DFG; Clinician
                      Scientist Program UMEA); Else Kröner-Fresenius-Stiftung
                      (EKFS; Medical Scientist Academy UMESciA).},
      keywords     = {Biomarker (Other) / Immune checkpoint inhibition (Other) /
                      Melanoma (Other) / Therapy outcome (Other) / Tumor PD-L1
                      (Other)},
      cin          = {A370 / ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)A370-20160331 / I:(DE-He78)ED01-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37660535},
      doi          = {10.1016/j.ebiom.2023.104774},
      url          = {https://inrepo02.dkfz.de/record/282517},
}