title: Outcomes after combined modality therapy for EGFR-mutant and wild-type locally advanced NSCLC.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutations identify a unique biological subtype of non-small cell lung cancer (NSCLC). Treatment outcomes for EGFR-mutant locally advanced NSCLC patients have not been well described.
  
  
  METHODS
  We retrospectively examined outcomes after combined modality therapy including thoracic radiation therapy (RT) in 123 patients with locally advanced NSCLC and known EGFR mutation status. Outcomes were compared using Kaplan-Meier analysis, the log-rank test, and multivariate Cox regression models.
  
  
  RESULTS
  All 123 patients underwent thoracic RT; 25% had tumors with EGFR mutations and 94% had stage III disease. Overall, 81% received chemotherapy concurrent with RT and 55% underwent surgical resection. With a median follow-up of 27.5 months, the overall survival (OS) rate was significantly higher in patients with EGFR-mutant tumors than in those with wild-type EGFR tumors (2-year estimate: 92.6% versus 69.0%; p = .04). The 2-year relapse-free survival and distant recurrence rates did not differ significantly by genotype. The 2-year locoregional recurrence rate (LRR) was significantly lower in EGFR-mutant than in wild-type EGFR patients (17.8% versus 41.7%; p = .005). EGFR-mutant genotype was associated with a lower risk for LRR on multivariate analysis, but not OS, after adjusting for surgery and other potential confounders.
  
  
  CONCLUSIONS
  We observed that EGFR-mutant patients with locally advanced NSCLC treated with RT had lower rates of LRR than wild-type EGFR patients, raising the hypothesis that EGFR mutations may confer sensitivity to RT and/or chemotherapy. The association between mutation status and OS after combined modality therapy was less robust. Our data may serve as a useful baseline estimate of outcomes by EGFR genotype for future prospective studies.
authors.affiliation: Harvard Radiation Oncology Program, Boston, Massachusetts, USA.
authors.forename: Raymond H
authors.initials: RH
authors.lastname: Mak
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Doran
authors.forename: Alona
authors.initials: A
authors.lastname: Muzikansky
authors.forename: Josephine
authors.initials: J
authors.lastname: Kang
authors.forename: Joel W
authors.initials: JW
authors.lastname: Neal
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Baldini
authors.forename: Noah C
authors.initials: NC
authors.lastname: Choi
authors.forename: Henning
authors.initials: H
authors.lastname: Willers
authors.forename: David M
authors.initials: DM
authors.lastname: Jackman
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy; D003131:Combined Modality Therapy; D023381:Endpoint Determination; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D066246:ErbB Receptors