title: Diverse effects of combined radiotherapy and EGFR inhibition with antibodies or TK inhibitors on local tumour control and correlation with EGFR gene expression.
abstract: OBJECTIVE
  To compare functional effects of combined irradiation and EGFR inhibition in different HNSCC tumour models in vivo with the results of molecular evaluations, aiming to set a basis for the development of potential biomarkers for local tumour control.
  
  
  METHODS
  In five HNSCC tumour models, all wild-type for EGFR and KRAS, the effect of radiotherapy alone (30 fractions/6 weeks) and with simultaneous cetuximab or erlotinib treatment on local tumour control were evaluated and compared with molecular data on western blot, immunohistochemistry and fluorescence-in situ-hybridisation (FISH).
  
  
  RESULTS
  Erlotinib and cetuximab alone significantly prolonged tumour growth time in 4/5 tumour models. Combined irradiation and cetuximab treatment significantly improved local tumour control in 3/5 tumour models, whereas erlotinib did not alter local tumour control in any of the tumour models. The amount of the cetuximab-effect on local tumour control significantly correlated with the EGFR/CEP-7 ratios obtained by FISH.
  
  
  CONCLUSIONS
  Both drugs prolonged growth time in most tumour models, but only application of cetuximab during irradiation significantly improved local tumour control in 3/5 tumour models. The significant correlation of this curative effect with the genetic EGFR expression measured by FISH will be further validated in preclinical and clinical studies.
authors.affiliation: OncoRay-National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Gurtner
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Deuse
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bütof
authors.forename: Katja
authors.initials: K
authors.lastname: Schaal
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eicheler
authors.forename: Reinhard
authors.initials: R
authors.lastname: Oertel
authors.forename: Reidar
authors.initials: R
authors.lastname: Grenman
authors.forename: Howard
authors.initials: H
authors.lastname: Thames
authors.forename: Ala
authors.initials: A
authors.lastname: Yaromina
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
authors.forename: Mechthild
authors.initials: M
authors.lastname: Krause
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D016015:Logistic Models; D051379:Mice; D008819:Mice, Nude; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D059016:Tumor Microenvironment
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000068818:Cetuximab