title: EGFR mutations are associated with favorable intracranial response and progression-free survival following brain irradiation in non-small cell lung cancer patients with brain metastases.
abstract: BACKGROUND
  The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is associated with increased radiosensitivity in vitro. However, the results from clinical studies regarding the radiosensitivity in NSCLC with mutant EGFR are inconclusive. We retrospectively analyzed our NSCLC patients who had been regularly followed up by imaging studies after irradiation for brain metastases, and investigated the impact of EGFR mutations on radiotherapy (RT).
  
  
  METHODS
  Forty-three patients with brain metastases treated with RT, together with EGFR mutation status, demographics, smoking history, performance status, recursive partitioning analysis (RPA) class, tumor characteristics, and treatment modalities, were included. Radiological images were taken at 1 to 3 months after RT, and 3 to 6 months thereafter. Radiographic response was evaluated by RECIST criteria version 1.1 according to the intracranial images before and after RT. Log-rank test and Cox regression model were used to correlate EGFR mutation status and other clinical features with intracranial radiological progression-free survival (RPFS) and overall survival (OS).
  
  
  RESULTS
  The median follow-up duration was 15 months. Patients with mutant EGFR had higher response rates to brain RT than those with wild-type EGFR (80% vs. 46%; p = 0.037). Logistic regression analysis showed that EGFR mutation status is the only predictor for treatment response (p = 0.032). The median intracranial RPFS was 18 months (95% CI = 8.33-27.68 months). In Cox regression analysis, mutant EGFR (p = 0.025) and lower RPA class (p = 0.026) were associated with longer intracranial RPFS. EGFR mutation status (p = 0.061) and performance status (p = 0.076) had a trend to predict OS.
  
  
  CONCLUSIONS
  Mutant EGFR in NSCLC patients is an independent prognostic factor for better treatment response and longer intracranial RPFS following RT for brain metastases.
authors.affiliation: Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taiwan.
authors.forename: Hsin-Lun
authors.initials: HL
authors.lastname: Lee
authors.forename: Tao-Sang
authors.initials: TS
authors.lastname: Chung
authors.forename: Lai-Lei
authors.initials: LL
authors.lastname: Ting
authors.forename: Jo-Ting
authors.initials: JT
authors.lastname: Tsai
authors.forename: Shang-Wen
authors.initials: SW
authors.lastname: Chen
authors.forename: Jeng-Fong
authors.initials: JF
authors.lastname: Chiou
authors.forename: Henry Wing-Cheung
authors.initials: HW
authors.lastname: Leung
authors.forename: H Eugene
authors.initials: HE
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D016371:Cranial Irradiation; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors