% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @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}, }