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@ARTICLE{Nicolay:168384,
      author       = {N. Nicolay$^*$ and A. Rühle$^*$ and N. Wiedenmann$^*$ and
                      G. Niedermann$^*$ and M. Mix and W. A. Weber and D.
                      Baltas$^*$ and M. Werner$^*$ and G. Kayser$^*$ and A.-L.
                      Grosu$^*$},
      title        = {{L}ymphocyte {I}nfiltration {D}etermines the
                      {H}ypoxia-{D}ependent {R}esponse to {D}efinitive
                      {C}hemoradiation in {H}ead-and-{N}eck {C}ancer: {R}esults
                      from a {P}rospective {I}maging {T}rial.},
      journal      = {Journal of nuclear medicine},
      volume       = {62},
      number       = {4},
      issn         = {2159-662X},
      address      = {New York, NY},
      publisher    = {Soc.},
      reportid     = {DKFZ-2021-00871},
      pages        = {471 - 478},
      year         = {2021},
      note         = {#EA:E055#},
      abstract     = {Tumor hypoxia in head-and-neck squamous cell carcinoma
                      (HNSCC) leads to an immunosuppressive microenvironment and
                      reduces the response to radiotherapy. In this prospective
                      imaging trial, we investigated potential interactions
                      between functional hypoxia imaging and infiltrating
                      lymphocyte levels as a potential predictor for treatment
                      response in HNSCC patients. Methods: In total, 49 patients
                      receiving definitive chemoradiation for locally advanced
                      HNSCCs underwent pretherapeutic biopsies and peritherapeutic
                      hypoxia imaging using 18F-misonidazole PET at weeks 0, 2,
                      and 5 during chemoradiation. Hematoxylin-eosin and
                      immunohistochemical stainings for tumor-infiltrating
                      lymphocytes, tissue-based hypoxia, and microvascular markers
                      were analyzed and correlated with the longitudinal hypoxia
                      dynamics and patient outcomes. Results: High levels of
                      tumor-infiltrating total lymphocytes correlated with
                      superior locoregional control (LRC) (hazard ratio [HR],
                      0.279; P = 0.011) and progression-free survival (PFS) (HR,
                      0.276; P = 0.006). Similarly, early resolution of
                      18F-misonidazole PET-detected tumor hypoxia quantified by
                      18F-misonidazole dynamics between weeks 0 and 2 of
                      chemoradiation was associated with improved LRC (HR, 0.321;
                      P = 0.015) and PFS (HR, 0.402; P = 0.043). Outcomes in the
                      favorable early hypoxia resolution subgroup significantly
                      depended on infiltrating lymphocyte counts, with patients
                      who showed both an early hypoxia response and high
                      lymphocyte infiltration levels exhibiting significantly
                      improved LRC (HR, 0.259; P = 0.036) and PFS (HR, 0.242; P =
                      0.017) compared with patients with an early hypoxia response
                      but low lymphocyte counts. These patients exhibited
                      oncologic results comparable to those of patients with no
                      hypoxia response within the first 2 wk of chemoradiation.
                      Conclusion: This analysis established a clinical
                      hypoxia-immune score that predicted treatment responses and
                      outcomes in HNSCC patients undergoing chemoradiation and may
                      help to devise novel concepts for biology-driven
                      personalization of chemoradiation.},
      keywords     = {FMISO PET (Other) / chemoradiation (Other) / head-and-neck
                      cancer (Other) / hypoxia (Other) / immune system (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:32859699},
      doi          = {10.2967/jnumed.120.248633},
      url          = {https://inrepo02.dkfz.de/record/168384},
}