title: Elevated basal antibody-dependent cell-mediated cytotoxicity (ADCC) and high epidermal growth factor receptor (EGFR) expression predict favourable outcome in patients with locally advanced head and neck cancer treated with cetuximab and radiotherapy.
abstract: BACKGROUND
  Antibody-dependent cell-mediated cytotoxicity (ADCC) may contribute to the antitumor activity of cetuximab. However, the extent of this contribution is unclear. In this study, we investigated the impact of baseline ADCC on the outcome of patients with locally advanced squamous cell carcinoma treated with cetuximab and radiotherapy.
  
  
  METHODS
  We determined baseline ADCC in 28 patients treated with cetuximab and radiotherapy and in 15 patients treated with chemoradiation. We linked the values observed with complete response and with overall survival. We also considered the role of epidermal growth factor receptor (EGFR) expression and studied the combined effect of EGFR and ADCC.
  
  
  RESULTS
  We observed a wide range of baseline values of ADCC. Complete response did not correlate with either ADCC or EGFR expression. However, when ADCC and EGFR were considered together using a mixed score, they significantly correlated with achieving a complete response (p = 0.04). High baseline ADCC significantly correlated with outcome compared to low (p = 0.03), but not in patients treated without cetuximab. Patients showing high baseline levels of both ADCC and EGFR3+ achieved the best outcome compared to the others (p = 0.02).
  
  
  CONCLUSIONS
  In this study, patients treated with cetuximab and radiotherapy, showing high baseline of both ADCC and EGFR3+, have significant higher probability of achieving a complete response and a long overall survival compared to the others.
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, via Carle 25, 12100, Cuneo, Italy. lauretta.lattanzio@gmail.com.
authors.forename: Laura
authors.initials: L
authors.lastname: Lattanzio
authors.affiliation: Medical Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Nerina
authors.initials: N
authors.lastname: Denaro
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, via Carle 25, 12100, Cuneo, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vivenza
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, via Carle 25, 12100, Cuneo, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Varamo
authors.affiliation: Pathology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Strola
authors.affiliation: Pathology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Fortunato
authors.affiliation: Oncopharmacology Unit, Centre A. Lacassagne, Nice, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Chamorey
authors.affiliation: Pathology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Comino
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, via Carle 25, 12100, Cuneo, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Monteverde
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, via Carle 25, 12100, Cuneo, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Lo Nigro
authors.affiliation: Oncopharmacology Unit, Centre A. Lacassagne, Nice, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Milano
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, via Carle 25, 12100, Cuneo, Italy.|Medical Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Merlano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000920:Antibody-Dependent Cell Cytotoxicity; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: ADCC; Cetuximab; EGFR; Head and neck cancer; Outcome