title: Monitoring of circulating tumor cells and their expression of EGFR/phospho-EGFR during combined radiotherapy regimens in locally advanced squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  The numbers of circulating tumor cells (CTCs) and their expression/activation of epidermal growth factor receptor (EGFR) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck (SCCHN) were determined.
  
  
  METHODS
  Peripheral blood samples from SCCHN patients with locally advanced stage IVA/B disease who were treated with concurrent radiochemotherapy or induction chemotherapy followed by bioradiation with cetuximab were included in this study. Using flow cytometry, the absolute number of CTCs per defined blood volume as well as their expression of EGFR and its phosphorylated form (pEGFR) during the course of treatment were assessed.
  
  
  RESULTS
  Before treatment, we detected ≥1 CTC per 3.75 mL blood in 9 of 31 patients (29%). Basal expression of EGFR was detected in 100% and pEGFR in 55% of the CTC+ cases. The frequency of CTC detection was not influenced by induction chemotherapy. However, the number of CTC+ samples significantly increased after radiotherapy. This radiation-induced increase in CTC numbers was less pronounced when radiotherapy was combined with cetuximab compared to its combination with cisplatin/5-fluorouracil. The former treatment regimen was also more effective in reducing pEGFR expression in CTCs.
  
  
  CONCLUSIONS
  Definitive radiotherapy regimens of locally advanced SCCHN can increase the number of CTCs and might thus contribute to a systemic spread of tumor cells. Further studies are needed to evaluate the predictive value of the radiation-induced increase in CTC numbers and the persistent activation of the EGFR signalling pathway in individual CTC+ cases.
authors.affiliation: Translational Radiooncology Laboratory, Department of Radiooncology and Radiotherapy, Charité Campus Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany. ingeborg.tinhofer@charite.de
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Tinhofer
authors.forename: Tsvetana
authors.initials: T
authors.lastname: Hristozova
authors.forename: Carmen
authors.initials: C
authors.lastname: Stromberger
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilhoiz
authors.forename: Volker
authors.initials: V
authors.lastname: Budach
mesh_terms: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D000068818:Cetuximab; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000379:methods; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000528:radiation effects; D010766:Phosphorylation; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil