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@ARTICLE{Rhle:168136,
      author       = {A. Rühle$^*$ and A.-L. Grosu$^*$ and N. Wiedenmann$^*$ and
                      R. Stoian$^*$ and E. Haehl$^*$ and C. Zamboglou$^*$ and D.
                      Baltas$^*$ and M. Werner$^*$ and G. Kayser$^*$ and N.
                      Nicolay$^*$},
      title        = {{I}mmunohistochemistry-based hypoxia-immune prognostic
                      classifier for head-and-neck cancer patients undergoing
                      chemoradiation - {P}ost-hoc analysis from a prospective
                      imaging trial.},
      journal      = {Radiotherapy and oncology},
      volume       = {159},
      issn         = {0167-8140},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2021-00704},
      pages        = {75-81},
      year         = {2021},
      note         = {2021 Mar 19;159:75-81 / #EA:E055#LA:E055#},
      abstract     = {As both tumor hypoxia and an immunosuppressing tumor
                      microenvironment hamper the anti-tumor activity of
                      radiotherapy in head-and-neck squamous cell carcinoma
                      (HNSCC), we aimed to develop an immunohistochemistry-based
                      hypoxia-immune classifier.39 patients receiving definitive
                      chemoradiation for HNSCC within a prospective trial were
                      included in this analysis. Baseline tumor samples were
                      analyzed for the hypoxia marker carbonic anhydrase IX (CAIX)
                      and tumor-infiltrating lymphocytes (TILs) and were
                      correlated with [18F]-misonidazole ([18F]FMISO) PET
                      measurements. The impact of the biomarkers on the
                      locoregional control (LRC) was examined using Cox analyses
                      and concordance index statistics.Low CAIX (HR=0.352,
                      $95\%CI$ 0.124-1.001, p=0.050) and high TIL levels
                      (HR=0.308, $95\%CI$ 0.114-0.828, p=0.020) were independent
                      parameters for improved LRC and did not correlate with each
                      other (Spearman's ρ=0.034, p=0.846). Harrell's C was 0.66
                      for CAIX and TIL levels alone and 0.71 for the combination.
                      2-year LRC was $73\%,$ $62\%$ and $11\%$ for the
                      prognostically good (CAIXlow/TILhigh), intermediate
                      (CAIXlow/TILlow or CAIXhigh/TILhigh) and poor groups
                      (CAIXhigh/TILlow), respectively (p=0.001). Focusing on T
                      lymphocytes, the hypoxia-immune classifier could still
                      stratify between favorable (CAIXlow/CD3+ TILhigh),
                      intermediate (CAIXlow/CD3+ TILlow or CAIXhigh/CD3+ TILhigh)
                      and poor subgroups (CAIXhigh/CD3+ TILlow) with a 2-year LRC
                      of $80\%,$ $59\%$ and $14\%,$ respectively (p=0.001). There
                      was a positive correlation between baseline CAIX levels and
                      [18F]FMISO SUV in week 2 of chemoradiation (ρ=0.324,
                      p=0.050), indicating an association between higher baseline
                      CAIX expression and tumor hypoxia persistence.We developed a
                      clinically feasible hypoxia-immune prognostic classifier for
                      HNSCC patients based on pre-treatment immunohistochemistry.
                      However, external validation is required to determine the
                      prognostic value and the potential usage for personalized
                      radiation oncology.},
      keywords     = {Carbonic anhydrase IX (Other) / FMISO PET (Other) /
                      Head-and-neck squamous cell carcinoma (Other) / Hypoxia
                      (Other) / Radiotherapy biomarker (Other) /
                      Tumor-infiltrating lymphocytes (Other)},
      cin          = {FR01 / E055},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331 / I:(DE-He78)E055-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33753155},
      doi          = {10.1016/j.radonc.2021.03.014},
      url          = {https://inrepo02.dkfz.de/record/168136},
}