title: Residual γH2AX foci predict local tumour control after radiotherapy.
abstract: OBJECTIVE
  Evaluation of micromilieu-dependent quantified γH2AX foci as a potential predictive biomarker in well-oxygenated tumour areas in 9 HNSCC xenograft models in vivo.
  
  
  METHODS
  GammaH2AX foci were quantified in perfused tumour areas 30 min (initial γH2AX foci) and 24 h (residual γH2AX foci) after exposure to a single dose of 4 Gy. The initial and residual normalised γH2AX foci were correlated with TCD50 after single dose irradiation under clamped blood flow (SDclamp) or a fractionated irradiation setting under ambient blood flow (fx).
  
  
  RESULTS
  A significant negative correlation between initial and residual normalised γH2AX foci and TCD50 SDclamp and TCD50 fx for 9 HNSCC tumour xenograft models in vivo was found. Residual normalised γH2AX foci showed higher intertumoural variability and their correlation with TCD50 was more robust.
  
  
  CONCLUSIONS
  For the first time a significant negative correlation between γH2AX foci and local tumour control after irradiation has been demonstrated. Our results underline the potential of residual γH2AX foci as a predictive biomarker for local tumour control after radiotherapy.
authors.affiliation: German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Radiation Oncology and OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koch
authors.forename: Katharina
authors.initials: K
authors.lastname: Höhne
authors.forename: Cläre
authors.initials: C
authors.lastname: von Neubeck
authors.forename: Howard D
authors.initials: HD
authors.lastname: Thames
authors.forename: Ala
authors.initials: A
authors.lastname: Yaromina
authors.forename: Jochen
authors.initials: J
authors.lastname: Dahm-Daphi
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
authors.forename: Mechthild
authors.initials: M
authors.lastname: Krause
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006657:Histones / Q000032:analysis*; D006801:Humans; D051379:Mice; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C468783:H2AX protein, human; D006657:Histones
keywords: Biomarker; DNA repair; Local tumour control; Radiotherapy; Tumour micromilieu; γH2AX