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@ARTICLE{Tawk:275441,
      author       = {B. Tawk$^*$ and K. Rein$^*$ and C. Schwager$^*$ and M.
                      Knoll$^*$ and U. Wirkner$^*$ and J. Hörner-Rieber$^*$ and
                      J. Liermann$^*$ and I. Kurth$^*$ and P. Balermpas$^*$ and C.
                      Roedel$^*$ and A. Linge$^*$ and S. Loeck$^*$ and F.
                      Lohaus$^*$ and I. Tinhofer$^*$ and M. Krause$^*$ and M.
                      Stuschke$^*$ and A.-L. Grosu$^*$ and D. Zips$^*$ and S. E.
                      Combs$^*$ and C. Belka$^*$ and A. Stenzinger$^*$ and C.
                      Herold-Mende and M. Baumann$^*$ and P. Schirmacher$^*$ and
                      J. Debus$^*$ and A. Abdollahi$^*$},
      title        = {{DNA}-{M}ethylome based {T}umor {H}ypoxia {C}lassifier
                      {I}dentifies {HPV}-negative {H}ead $\&$ {N}eck {C}ancer
                      {P}atients at {R}isk for {L}ocoregional {R}ecurrence {A}fter
                      {P}rimary {R}adiochemotherapy.},
      journal      = {Clinical cancer research},
      volume       = {29},
      number       = {16},
      issn         = {1078-0432},
      address      = {Philadelphia, Pa. [u.a.]},
      publisher    = {AACR},
      reportid     = {DKFZ-2023-00764},
      pages        = {3051-3064},
      year         = {2023},
      note         = {#EA:E210#LA:E210# / 2023 Aug 15;29(16):3051-3064},
      abstract     = {Tumor hypoxia is a paradigmatic negative prognosticator of
                      treatment resistance in Head and Neck Squamous Cell
                      Carcinoma (HNSCC). The lack of robust and reliable hypoxia
                      classifiers limits the adaptation of stratified therapies.
                      We hypothesized that the tumor DNA methylation landscape
                      might indicate epigenetic reprogramming induced by chronic
                      intratumoral hypoxia.A DNA methylome-based tumor hypoxia
                      classifier (Hypoxia-M) was trained in the TCGA-HNSCC cohort
                      based on matched assignments using gene expression-based
                      signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated
                      in a multicenter DKTK-ROG trial consisting of Human
                      Papilloma Virus (HPV)-negative HNSCC patients treated with
                      primary radiochemotherapy (RCHT).While hypoxia-GSEs failed
                      to stratify patients in the DKTK-ROG, Hypoxia-M was
                      independently prognostic for local recurrence (LR, HR=4.3,
                      p=0.001) and overall survival (OS, HR=2.34, p=0.03) but not
                      distant metastasis (DM) after RCHT in the both cohorts.
                      Hypoxia-M status was inversely associated with CD8 T-cells
                      infiltration in both cohorts. Hypoxia-M was further
                      prognostic in the TCGA-PanCancer cohort (HR=1.83, p=0.04),
                      underscoring the breadth of this classifier for predicting
                      tumor hypoxia status.Our findings highlight an unexplored
                      avenue for DNA Methylation-based classifiers as biomarkers
                      of tumoral hypoxia for identifying high-risk features in
                      patients with HNSCC tumors.Retrospective observational study
                      from the German Cancer Consortium (DKTK-ROG), not
                      interventional.},
      cin          = {E210 / E050 / DD01 / FM01 / BE01 / ED01 / FR01 / TU01 /
                      MU01 / E220 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)E210-20160331 / I:(DE-He78)E050-20160331 /
                      I:(DE-He78)DD01-20160331 / I:(DE-He78)FM01-20160331 /
                      I:(DE-He78)BE01-20160331 / I:(DE-He78)ED01-20160331 /
                      I:(DE-He78)FR01-20160331 / I:(DE-He78)TU01-20160331 /
                      I:(DE-He78)MU01-20160331 / I:(DE-He78)E220-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37058257},
      doi          = {10.1158/1078-0432.CCR-22-3790},
      url          = {https://inrepo02.dkfz.de/record/275441},
}