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@ARTICLE{Rhle:177407,
      author       = {A. Rühle$^*$ and N. Wiedenmann$^*$ and J. T. Fennell$^*$
                      and M. Mix and J. Ruf and R. Stoian$^*$ and A. R.
                      Thomsen$^*$ and P. Vaupel$^*$ and D. Baltas$^*$ and A.-L.
                      Grosu$^*$ and N. Nicolay$^*$},
      title        = {{I}nterleukin-6 as surrogate marker for imaging-based
                      hypoxia dynamics in patients with head-and-neck cancers
                      undergoing definitive chemoradiation-results from a
                      prospective pilot trial.},
      journal      = {European journal of nuclear medicine and molecular imaging},
      volume       = {49},
      number       = {5},
      issn         = {1619-7089},
      address      = {Heidelberg [u.a.]},
      publisher    = {Springer-Verl.},
      reportid     = {DKFZ-2021-02499},
      pages        = {1650-1660},
      year         = {2022},
      note         = {#EA:E055#LA:E055# / 2022 Apr;49(5):1650-1660},
      abstract     = {Intratumoral hypoxia increases resistance of head-and-neck
                      squamous cell carcinoma (HNSCC) to radiotherapy. [18F]FMISO
                      PET imaging enables noninvasive hypoxia monitoring, though
                      requiring complex logistical efforts. We investigated the
                      role of plasma interleukin-6 (IL-6) as potential surrogate
                      parameter for intratumoral hypoxia in HNSCC using [18F]FMISO
                      PET/CT as reference.Within a prospective trial, serial blood
                      samples of 27 HNSCC patients undergoing definitive
                      chemoradiation were collected to analyze plasma IL-6 levels.
                      Intratumoral hypoxia was assessed in treatment weeks 0, 2,
                      and 5 using [18F]FMISO PET/CT imaging. The association
                      between PET-based hypoxia and IL-6 was examined using
                      Pearson's correlation and multiple regression analyses, and
                      the diagnostic power of IL-6 for tumor hypoxia response
                      prediction was determined with receiver-operating
                      characteristic analyses.Mean IL-6 concentrations were 15.1,
                      19.6, and 31.0 pg/mL at baseline, week 2 and week 5,
                      respectively. Smoking (p=0.050) and reduced performance
                      status (p=0.011) resulted in higher IL-6 levels, whereas
                      tumor (p=0.427) and nodal stages (p=0.334), tumor
                      localization (p=0.439), and HPV status (p=0.294) had no
                      influence. IL-6 levels strongly correlated with the
                      intratumoral hypoxic subvolume during treatment (baseline:
                      r=0.775, p<0.001; week 2: r=0.553, p=0.007; week 5: r=0.734,
                      p<0.001). IL-6 levels in week 2 were higher in patients with
                      absent early tumor hypoxia response (p=0.016) and predicted
                      early hypoxia response (AUC=0.822, p=0.031). Increased IL-6
                      levels at week 5 resulted in a trend towards reduced
                      progression-free survival (p=0.078) and overall survival
                      (p=0.013).Plasma IL-6 is a promising surrogate marker for
                      tumor hypoxia dynamics in HNSCC patients and may facilitate
                      hypoxia-directed personalized radiotherapy concepts.The
                      prospective trial was registered in the German Clinical
                      Trial Register (DRKS00003830). Registered 20 August 2015.},
      keywords     = {Biomarker (Other) / FMISO-PET (Other) / Head-and-neck
                      cancer (Other) / Hypoxia (Other) / Interleukin-6 (Other) /
                      Radiotherapy (Other)},
      cin          = {E055 / FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)E055-20160331 / I:(DE-He78)FR01-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34773163},
      doi          = {10.1007/s00259-021-05602-x},
      url          = {https://inrepo02.dkfz.de/record/177407},
}