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@ARTICLE{Zschaeck:166144,
      author       = {S. Zschaeck$^*$ and K. Zöphel$^*$ and A. Seidlitz$^*$ and
                      D. Zips$^*$ and J. Kotzerke$^*$ and M. Baumann$^*$ and E.
                      Troost$^*$ and S. Löck$^*$ and M. Krause$^*$},
      title        = {{G}eneration of biological hypotheses by functional imaging
                      links tumor hypoxia to radiation induced tissue
                      inflammation/glucose uptake in head and neck cancer.},
      journal      = {Radiotherapy and oncology},
      volume       = {155},
      issn         = {0167-8140},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2020-02652},
      pages        = {204 - 211},
      year         = {2020},
      abstract     = {Positron emission tomography (PET) is a functional imaging
                      modality which is able to deliver tracer specific biological
                      information, e.g. about glucose uptake, inflammation or
                      hypoxia of tumors. We performed a proof-of-principle study
                      that used different tracers and expanded the analytical
                      scope to non-tumor structures to evaluate tumor-host
                      interactions.Based on a previously reported prospective
                      imaging study on 50 patients treated with curative intent
                      chemoradiation (CRT) for head and neck squamous cell
                      carcinoma, PET-based hypoxia and normal tissue inflammation
                      measured by repeat 18F-fluoromisonidazole (FMISO) PET and
                      18F-fluorodesoxyglucose (FDG) PET, respectively, were
                      correlated using the Spearman correlation coefficient R. PET
                      parameters determined before and during CRT (week 1, 2 and
                      5), were associated with local tumor control and overall
                      survival.Tumor hypoxia at all measured times showed an
                      inverse correlation with mid-treatment FDG-uptake of
                      non-tumor affected oral (sub-)mucosa with R values between
                      -0.35 and -0.6 (all p < 0.05). Mucosal FDG-uptake and
                      mucosal hypoxia correlated positively but weaker (R values
                      between 0.2 and 0.45). More tumor hypoxia in FMISO-PET (week
                      2) and less FDG-uptake of (sub-)mucosa in FDG-PET (week 4)
                      were significantly associated with worse LC (FMISO TBRpeak:
                      HR = 1.72, p = 0.030; FDG SUVmean: HR = 0.23,
                      p = 0.025) and OS (FMISO TBRpeak: HR = 1.71,
                      p = 0.007; FDG SUVmean: HR = 0.30, p = 0.003).
                      Multivariable models including both parameters showed
                      improved performance, suggesting that these modalities still
                      bear distinct biological information despite their strong
                      inter-correlation.We report first clinical evidence that
                      tumor hypoxia is inversely correlated with increased
                      FDG-uptake during radiation, potentially expressing
                      inflammation. This observation merits further research and
                      may have important implication for future research on tumor
                      hypoxia and radio-immunology. Our study demonstrates that
                      functional imaging can be utilized to assess complex
                      tumor-host interactions and generate novel biological
                      insights in vivo vero.},
      cin          = {DD01 / TU01 / M010 / E220},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331 / I:(DE-He78)TU01-20160331 /
                      I:(DE-He78)M010-20160331 / I:(DE-He78)E220-20160331},
      pnm          = {315 - Imaging and radiooncology (POF3-315)},
      pid          = {G:(DE-HGF)POF3-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33252044},
      doi          = {10.1016/j.radonc.2020.10.030},
      url          = {https://inrepo02.dkfz.de/record/166144},
}