title: Prognostic value of epidermal growth factor receptor expression in patients with advanced stage nasopharyngeal carcinoma treated with induction chemotherapy and radiotherapy.
abstract: OBJECTIVE
  A retrospective study was performed to correlate the expression of epidermal growth factor receptor (EGFR) with treatment outcome in advanced stage nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  The study population comprised 54 of 92 patients with American Joint Committee on Cancer Stage III-IV NPC with sufficient pretreatment tumor biopsy specimens for study. Immunohistochemical staining was performed to evaluate the extent and intensity of EGFR expression. All patients were treated by induction chemotherapy with two to three cycles of cisplatin 60 mg/m(2) and epirubicin 110 mg/m(2) every 3 weeks followed by radiotherapy. The median follow-up time was 52 months for all patients and 99 months for surviving patients.
  
  
  RESULTS
  EGFR expression was present in 89% of cases. EGFR intensity was negative in 11%, weak in 43%, moderate in 13%, and strong in 33%. The EGFR extent was <5% in 15%, > or =5% but <25% in 13%, and > or =25% in 72%. No correlation was found between EGFR expression and T stage, N stage, stage group, nodal size, gender, and age. No statistically significant differences in chemotherapy response rates were found in patients with different EGFR intensity and extent. EGFR extent > or =25% was associated with a significantly poorer treatment outcome. The 5-year disease-specific survival, relapse-free survival, locoregional relapse-free, and distant metastasis-free rate in patients with EGFR extent > or =25% was 48%, 36%, 60%, and 55%, respectively. The corresponding rates in patients with EGFR extent <25% were 86%, 80%, 93%, and 86%. The differences were all statistically significant, except for distant metastasis. No statistically significant differences in relapse-free and disease-specific survival rates were found among patients with differing EGFR intensity. In multivariate analysis, EGFR extent was the only independent factor that predicted for disease relapse, locoregional failure, and cancer death.
  
  
  CONCLUSIONS
  Our study results showed that EGFR expression was common in advanced stage NPC, and the expression did not correlate with tumor or nodal stage. Correlative analysis showed that EGFR extent was a strong, independent prognostic factor that determined locoregional control, relapse-free survival, and disease-specific survival in Stage III-IV NPC treated with induction chemotherapy and radiotherapy. Our findings suggest that EGFR expression status can identify a subgroup of patients within advanced stage disease that will have a poor outcome after induction chemotherapy and radiotherapy. Whether this patient subgroup will benefit from an alternate treatment strategy and anti-EGFR-targeted treatment requires additional studies.
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China. dttchua@hkucc.hku.hk
authors.forename: Daniel T T
authors.initials: DT
authors.lastname: Chua
authors.forename: John M
authors.initials: JM
authors.lastname: Nicholls
authors.forename: Jonathan S T
authors.initials: JS
authors.lastname: Sham
authors.forename: Gordon K H
authors.initials: GK
authors.lastname: Au
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D015251:Epirubicin / Q000008:administration & dosage; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D009363:Neoplasm Proteins; D015251:Epirubicin; D066246:ErbB Receptors; D002945:Cisplatin