title: EGFR tyrosine kinase inhibitors versus cranial radiation therapy for EGFR mutant non-small cell lung cancer with brain metastases: a systematic review and meta-analysis.
abstract: OBJECTIVE
  EGFR TKIs alone have demonstrated activity against intracranial disease in EGFR mutant non-small cell lung cancer (NSCLC). This study aimed to determine if upfront cranial radiotherapy improves intracranial disease control and survival outcomes in EGFR mutant NSCLC with brain metastases relative to TKIs alone.
  
  
  METHODS
  We searched MEDLINE and various conference proceedings from 2008 to July 2014 for eligible studies where patients received upfront cranial radiotherapy or TKIs alone. Outcomes of interest were overall intracranial disease response rate (ORR), four-month intracranial disease progression-free survival (PFS), two-year overall survival (OS) and neurological adverse events (AE). We used random effects models to pool outcomes across studies and compared them using interaction tests.
  
  
  RESULTS
  We found 12 non-comparative observational studies (n=363) with severe methodological limitations. Upfront cranial radiotherapy results in similar intracranial disease ORR (relative risk (RR) 0.93, 95% confidence interval (CI) 0.82-1.06; interaction p value (p)=0.53), improved four-month intracranial disease PFS (RR 1.06, 95% CI 1.00-1.12; p=0.03), improved two-year OS (RR 1.33, 95% CI 1.00-1.77; p=0.05) but caused more neurological AEs than TKIs alone.
  
  
  CONCLUSIONS
  There is evidence, albeit of low quality, that upfront cranial radiotherapy may improve intracranial disease control and survival outcomes compared with TKI alone.
authors.affiliation: Department of Radiation Oncology, National University Cancer Institute, Singapore, National University Health System, National University of Singapore, Singapore. Electronic address: yysoon01@gmail.com.
authors.forename: Yu Yang
authors.initials: YY
authors.lastname: Soon
authors.affiliation: Department of Radiation Oncology, National University Cancer Institute, Singapore, National University Health System, National University of Singapore, Singapore.
authors.forename: Cheng Nang
authors.initials: CN
authors.lastname: Leong
authors.affiliation: Department of Radiation Oncology, National University Cancer Institute, Singapore, National University Health System, National University of Singapore, Singapore.
authors.forename: Wee Yao
authors.initials: WY
authors.lastname: Koh
authors.affiliation: Department of Radiation Oncology, National University Cancer Institute, Singapore, National University Health System, National University of Singapore, Singapore.
authors.forename: Ivan Weng Keong
authors.initials: IW
authors.lastname: Tham
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary* / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D016371:Cranial Irradiation / Q000379:methods*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Epidermal growth factor receptor tyrosine kinase inhibitors; Non-small cell lung cancer; Stereotactic radiation therapy; Whole brain radiation therapy