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@ARTICLE{Eder:143911,
      author       = {T. Eder$^*$ and A. K. Hess and R. Konschak$^*$ and C.
                      Stromberger and K. Jöhrens and V. Fleischer and M.
                      Hummel$^*$ and P. Balermpas$^*$ and J. von der Grün$^*$ and
                      A. Linge$^*$ and F. A. Lohaus$^*$ and M. Krause$^*$ and M.
                      Baumann$^*$ and M. Stuschke$^*$ and D. Zips$^*$ and A. L.
                      Grosu$^*$ and A. Abdollahi$^*$ and J. Debus$^*$ and C.
                      Belka$^*$ and S. Pigorsch$^*$ and S. E. Combs$^*$ and V.
                      Budach$^*$ and I. Tinhofer$^*$ and DKTK-ROG},
      title        = {{I}nterference of tumour mutational burden with outcome of
                      patients with head and neck cancer treated with definitive
                      chemoradiation: a multicentre retrospective study of the
                      {G}erman {C}ancer {C}onsortium {R}adiation {O}ncology
                      {G}roup.},
      journal      = {European journal of cancer},
      volume       = {116},
      issn         = {0959-8049},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2019-01469},
      pages        = {67 - 76},
      year         = {2019},
      abstract     = {Tumour mutational burden (TMB) estimated from whole exome
                      sequencing or comprehensive gene panels has previously been
                      established as predictive factor of response to immune
                      checkpoint inhibitors (ICIs). Its predictive value for the
                      efficacy of concurrent chemoradiation (cCRTX), a potential
                      combination partner of ICI, remains unknown.The accuracy of
                      TMB estimation by an in-house 327-gene panel was established
                      in the Cancer Genome Atlas (TCGA) head and neck squamous
                      cell carcinoma (HNSCC) data set. Interference of TMB with
                      outcome after cCRTX was determined in a multicentre cohort
                      of patients with locally advanced HNSCC uniformly treated
                      with cCRTX. Targeted next-generation sequencing was
                      successfully applied in 101 formalin-fixed,
                      paraffin-embedded pretreatment tumour samples. In a subset
                      of cases (n = 40), tumour RNA was used for immune-related
                      gene expression profiling by the nanoString platform. TMB
                      was correlated with TP53 genotype, human papilloma virus
                      (HPV) status, immune expression signatures and survival
                      parameters. Results were validated in the TCGA HNSCC
                      cohort.A high accuracy of TMB estimation by the 327-gene
                      panel was established. High TMB was significantly associated
                      with an increased prevalence of TP53 mutations and immune
                      gene expression patterns unrelated to T cell-inflamed gene
                      expression profiles. Kaplan-Meier analysis revealed
                      significantly reduced overall survival in the patient group
                      with high TMB (hazard ratio for death: 1.79, $95\%$
                      confidence interval: 1.02-3.14; P = 0.042) which remained
                      significant after correcting for confounding factors in the
                      multivariate model. The prognostic value of TMB was
                      confirmed in the TCGA HNSCC cohort.High TMB identifies HNSCC
                      patients with poor outcome after cCRTX who might
                      preferentially benefit from CRTX-ICI combinations.},
      cin          = {L201 / L501 / L301 / E220 / L401 / L801 / L601 / E210 /
                      E050 / L101 / L701},
      ddc          = {610},
      cid          = {I:(DE-He78)L201-20160331 / I:(DE-He78)L501-20160331 /
                      I:(DE-He78)L301-20160331 / I:(DE-He78)E220-20160331 /
                      I:(DE-He78)L401-20160331 / I:(DE-He78)L801-20160331 /
                      I:(DE-He78)L601-20160331 / I:(DE-He78)E210-20160331 /
                      I:(DE-He78)E050-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)L701-20160331},
      pnm          = {315 - Imaging and radiooncology (POF3-315)},
      pid          = {G:(DE-HGF)POF3-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31173964},
      doi          = {10.1016/j.ejca.2019.04.015},
      url          = {https://inrepo02.dkfz.de/record/143911},
}