title: Prognostic role of ERCC1 in advanced non-small-cell lung cancer: a systematic review and meta-analysis.
abstract: Small observational studies have demonstrated an association between high ERCC1 expression level and poor prognosis in advanced NSCLC treated with platinum-based chemotherapy. This meta-analysis presents pooled estimates of association from 11 studies. High ERCC1 patients had lower response rates and higher risk of death relative to low ERCC1 patients. These results support the prognostic significance of ERCC1 expression level in advanced NSCLC.
  
  
  BACKGROUND
  Observational studies have demonstrated an association between excision repair cross-complementation group 1 (ERCC1) expression level and health outcomes in patients with advanced non-small-cell lung cancer (NSCLC) treated with platinum-based regimens. This analysis presents pooled estimates of association from these studies to better elucidate the prognostic role of ERCC1 in advanced NSCLC.
  
  
  METHODS
  A systematic literature search was conducted using the MEDLINE, EMBASE, and American Society of Clinical Oncology (ASCO) annual meeting databases from June 1995 to December 2010. Included studies were evaluated for clinical, methodological, and statistical heterogeneity. Pooled analyses were conducted using fixed and random effects models.
  
  
  RESULTS
  In high ERCC1 expression versus low ERCC1 expression patients, pooled analysis results demonstrated a significantly lower response (risk ratio [RR], 0.80, 0.66-0.98) and significantly higher risk of death (hazard ratio [HR], 2.04, (1.48-2.80)), respectively. Subgroup analyses demonstrated significant heterogeneity in outcomes by ERCC1 measurement method (I(2): 90.7%, P = 0.001) and patient population ethnicity (I(2): 66%, P = 0.003).
  
  
  CONCLUSIONS
  This study's findings support the hypothesis that ERCC1 expression is associated with response rate and overall survival (OS) in patients with advanced NSCLC treated with platinum-based chemotherapy. Heterogeneity in subgroup analyses demonstrates the need for standardized methods to classify ERCC1 expression level, studies evaluating the association between ERCC1 expression and OS in non-Asian populations, and studies evaluating interaction between ERCC1 and other known prognostic factors in advanced NSCLC.
authors: University of Washington, Pharmaceutical Outcomes Research and Policy Program, Seattle, Washington 98195, USA. rothja@uw.edu
authors: Joshua A
authors: JA
authors: Roth
authors: Josh J
authors: JJ
authors: Carlson
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D015201:Meta-Analysis as Topic; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases