title: ERCC1 influence on the incidence of brain metastases in patients with non-squamous NSCLC treated with adjuvant cisplatin-based chemotherapy.
abstract: BACKGROUND
  We recently demonstrated that excision repair cross-complementing group 1 protein (ERCC1) is predictive of adjuvant cisplatin-based chemotherapy benefit in resected non-small-cell lung cancer (NSCLC). Non-squamous cell carcinomas (non-SCCs) carry an increased risk of brain metastases (BMs). We hypothesised that there might be an increased incidence of BMs in ERCC1-negative non-SCCs when treated with adjuvant cisplatin-based chemotherapy.
  
  
  METHODS
  Incidence of BMs and histoclinical parameters were analysed in a population of 761 patients enrolled in the International Adjuvant Lung Cancer Trial. A subgroup analysis was carried out in patients with ERCC1-negative non-SCCs.
  
  
  RESULTS
  Of 761 patients, 98 developed BMs alone or in association with other metastatic sites, with a 5-year incidence rate of 18.0% (14.7%-21.8%). In the multivariate analysis, the clinical parameters associated with the occurrence of BMs were the nodal status (P = 0.02) and histological type [give hazard ratio (HR) for non-squamous to quantify introduction assertion, P = 0.002]. Chemotherapy had no effect on BMs [HR = 1.4 (0.90-2.1), P = 0.14]. In patients with non-SCC histology (n = 335), adjuvant chemotherapy was associated with an increased risk of BMs [HR = 2.1 (1.01-4.3), P = 0.04] for ERCC1-negative tumours, whereas there was no evidence of an effect on BMs for ERCC1-positive tumours [HR = 1.1 (0.38-3.0), P = 0.90]. Nevertheless, these two effects are not different (P = 0.30 for interaction) possibly due to a lack of power in this subgroup.
  
  
  CONCLUSIONS
  This study suggests that adjuvant cisplatin-based chemotherapy is associated with an increased risk of BMs in patients with resected chemosensitive non-SCCs. If confirmed, these data could provide a rationale for new follow-up and/or prophylactic strategies.
authors.affiliation: Department of Medical Oncology.
authors.forename: B
authors.initials: B
authors.lastname: Besse
authors.affiliation: Department of Medical Oncology.
authors.forename: C
authors.initials: C
authors.lastname: Massard
authors.affiliation: Department of Statistics, Institut Gustave Roussy, Villejuif, France.
authors.forename: V
authors.initials: V
authors.lastname: Haddad
authors.affiliation: Department of Medical Oncology.
authors.forename: F
authors.initials: F
authors.lastname: Andre
authors.affiliation: Department of Statistics, Institut Gustave Roussy, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Dunant
authors.affiliation: Department of Internal Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Pirker
authors.affiliation: Department of Pathology; Department of Translational Research, Institut Gustave Roussy, Villejuif.
authors.forename: K A
authors.initials: KA
authors.lastname: Olaussen
authors.affiliation: Department of Pathology, Centre Hospitalier Universitaire Albert Michallon, Grenoble, France.
authors.forename: E
authors.initials: E
authors.lastname: Brambilla
authors.affiliation: Department of Pathology; Department of Translational Research, Institut Gustave Roussy, Villejuif.
authors.forename: P
authors.initials: P
authors.lastname: Fouret
authors.affiliation: Department of Medical Oncology. Electronic address: jean-charles.soria@igr.fr.
authors.forename: J C
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000209:etiology / Q000556:secondary* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin