title: Association between EGFR-TKI resistance and efficacy of radiotherapy for brain metastases from EGFR-mutant lung adenocarcinoma.
abstract: OBJECTIVE
  To clarify how patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) respond to radiotherapy (RT) for brain metastases.
  
  
  METHODS
  Forty-seven patients were divided into the following three groups: a TKI-naïve group with EGFR mutation (n=11), a TKI-resistant group with EGFR mutation (n=10), and an EGFR-wild-type group (n=26). Patients received stereotactic RT (n=23) or whole-brain RT (n=24).
  
  
  RESULTS
  The response rate for patients with TKI-resistant tumor at three months after RT tended to be lower (11%) than that of those who were TKI-naïve (82%, p=0.006) and for patients with wild-type EGFR (48%, p=0.10). On univariate analysis, central nervous system progression-free and overall survival were significantly shorter for patients with TKI-resistant tumors than for those who were TKI-naïve (p=0.018 and p=0.005, respectively). Multivariate analysis showed that TKI resistance was an independent predictor of poorer overall survival (p=0.011).
  
  
  CONCLUSIONS
  Acquired resistance to TKIs appears to be associated with low efficacy of brain RT.
authors.affiliation: Department of Radiology, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
authors.forename: Hidenari
authors.initials: H
authors.lastname: Hirata
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Nakamura
authors.forename: Naonobu
authors.initials: N
authors.lastname: Kunitake
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shioyama
authors.forename: Tomonari
authors.initials: T
authors.lastname: Sasaki
authors.forename: Saiji
authors.initials: S
authors.lastname: Ohga
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nonoshita
authors.forename: Tadamasa
authors.initials: T
authors.lastname: Yoshitake
authors.forename: Kaori
authors.initials: K
authors.lastname: Asai
authors.forename: Kouji
authors.initials: K
authors.lastname: Inoue
authors.forename: Akira
authors.initials: A
authors.lastname: Nagashima
authors.forename: Minoru
authors.initials: M
authors.lastname: Ono
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Honda
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors