title: The influence of epidermal growth factor receptor and tumor differentiation on the response to accelerated radiotherapy of squamous cell carcinomas of the head and neck in the randomized DAHANCA 6 and 7 study.
abstract: OBJECTIVE
  Reduction of the overall treatment time of radiotherapy has increased locoregional control and disease specific survival in squamous cell carcinomas of the head and neck (HNSCC), but the response is heterogeneous. EGFr is often overexpressed in HNSCC and has been related to the repopulation taking place during radiotherapy. The aim of the current study was to address the influence of EGFr and histopathological differentiation when the overall treatment time of radiotherapy was moderately reduced.
  
  
  METHODS
  Eight hundred and three patients with representative pretreatment tissue samples from the randomized DAHANCA 6 and 7 study of 5 vs. 6 fx/wk of radiotherapy. EGFr was visualized using immunohistochemistry and separated into high and low expression before correlation with clinical data.
  
  
  RESULTS
  Tumors with high EGFr (84%) responded better to moderately accelerated radiotherapy, than carcinomas with low EGFr, using locoregional control as endpoint and a similar pattern was seen, stratifying by well/moderate vs. poor tumor differentiation. Therefore, a combined parameter was constructed showing a more prominent separation of response: tumors with high EGFr and well/moderate differentiation did benefit from moderate acceleration of treatment regarding locoregional control, HR 0.54 (0.37-0.78), whereas such an effect was not seen in tumors with low EGFr and/or poor differentiation, HR 0.8 (0.51-1.25). These results reflected the disease specific survival as well and were confirmed in multivariable analyses.
  
  
  CONCLUSIONS
  Moderately accelerated fractionation is superior to conventional treatment in HNSCC but the response is heterogeneous and may be predicted by high expression of EGFr and well/moderate tumor differentiation.
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jesper G
authors.initials: JG
authors.lastname: Eriksen
authors.forename: Torben
authors.initials: T
authors.lastname: Steiniche
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000532:radiotherapy*; D002471:Cell Transformation, Neoplastic; D066246:ErbB Receptors / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D066246:ErbB Receptors