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@ARTICLE{Tawk:177034,
      author       = {B. Tawk$^*$ and U. Wirkner$^*$ and C. Schwager$^*$ and K.
                      Rein$^*$ and K. Zaoui and P. A. Federspil and S. Adeberg$^*$
                      and A. Linge$^*$ and U. Ganswindt$^*$ and J. Hess and K.
                      Unger and I. Tinhofer$^*$ and V. Budach$^*$ and F.
                      Lohaus$^*$ and M. Krause$^*$ and M. Guberina$^*$ and M.
                      Stuschke$^*$ and P. Balermpas$^*$ and C. Rödel$^*$ and A.
                      L. Grosu$^*$ and H. Schäfer$^*$ and D. Zips$^*$ and S. E.
                      Combs$^*$ and S. Pigorsch$^*$ and H. Zitzelsberger and P.
                      Baumeister and T. Kirchner$^*$ and M. Bewerunge-Hudler$^*$
                      and W. Weichert$^*$ and J. Hess$^*$ and E. Herpel$^*$ and C.
                      Belka$^*$ and M. Baumann$^*$ and J. Debus$^*$ and A.
                      Abdollahi$^*$},
      collaboration = {DKTK-ROG},
      title        = {{T}umor {DNA}-{M}ethylome derived {E}pigenetic
                      {F}ingerprint {I}dentifies {HPV}-negative {H}ead and {N}eck
                      {P}atients at {R}isk for {L}ocoregional {R}ecurrence after
                      {P}ostoperative {R}adiochemotherapy.},
      journal      = {International journal of cancer},
      volume       = {150},
      number       = {4},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2021-02262},
      pages        = {603-616},
      year         = {2022},
      note         = {#EA:E210#LA:E210# / 2022 Feb 15;150(4):603-616},
      abstract     = {Biomarkers with relevance for loco-regional therapy are
                      needed in Human Papillomavirus negative aka HPV(-) Head and
                      Neck Squamous Cell Carcinoma (HNSCC). Based on the premise
                      that DNA methylation pattern is highly conserved, we sought
                      to develop a reliable and robust methylome-based classifier
                      identifying HPV(-) HNSCC patients at risk for loco-regional
                      recurrence (LR) and all-event progression after
                      postoperative radiochemotherapy (PORT-C). The training
                      cohort consisted of HPVDNA negative HNSCC patients (n=128)
                      homogeneously treated with PORT-C in frame of the German
                      Cancer Consortium - Radiation Oncology Group (DKTK-ROG)
                      multicenter biomarker trial. DNA Methylation analysis was
                      performed using Illumina 450K and 850K-EPIC microarray
                      technology. The performance of the classifier was integrated
                      with a series of biomarkers studied in training set, namely
                      hypoxia-, 5-microRNA (5-miR)-, stem-cell gene-expression
                      signatures and immunohistochemistry (IHC)-based
                      immunological characterization of tumors
                      (CD3/CD8/PD-L1/PD1). Validation occurred in an independent
                      cohort of HPV(-) HNSCC patients, pooled from two German
                      centers (n=125). We identified a 38-methylation probe-based
                      HPV(-) Independent Classifier of disease Recurrence (HICR)
                      with high prognostic value for LR, distant metastases and
                      overall survival (p<10-9 ). HICR remained significant after
                      multivariate analysis adjusting for anatomical site, lymph
                      node extracapsular extension (ECE) and size (T-stage). HICR
                      high-risk tumors were enriched for younger patients with
                      hypoxic tumors (15-gene signature) and elevated 5-miR score.
                      After adjustment for hypoxia and 5-miR covariates, HICR
                      maintained predicting all endpoints. HICR provides a novel
                      mean for assessing the risk of LR in HPV(-) HNSCC patients
                      treated with PORT-C and opens a new opportunity for
                      biomarker-assisted stratification and therapy adaptation in
                      these patients. This article is protected by copyright. All
                      rights reserved.},
      keywords     = {DNA Methylation (Other) / Disease Recurrence (Other) / Head
                      and Neck Cancers (Other) / Radiotherapy (Other) /
                      Stratification (Other)},
      cin          = {E210 / HD01 / DD01 / MU01 / BE01 / ED01 / FM01 / FR01 /
                      TU01 / W110 / E220 / E050 / E221},
      ddc          = {610},
      cid          = {I:(DE-He78)E210-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)DD01-20160331 / I:(DE-He78)MU01-20160331 /
                      I:(DE-He78)BE01-20160331 / I:(DE-He78)ED01-20160331 /
                      I:(DE-He78)FM01-20160331 / I:(DE-He78)FR01-20160331 /
                      I:(DE-He78)TU01-20160331 / I:(DE-He78)W110-20160331 /
                      I:(DE-He78)E220-20160331 / I:(DE-He78)E050-20160331 /
                      I:(DE-He78)E221-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34648658},
      doi          = {10.1002/ijc.33842},
      url          = {https://inrepo02.dkfz.de/record/177034},
}