title: Impact of Deferring Radiation Therapy in Patients With Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Develop Brain Metastases.
abstract: To perform a retrospective analysis of patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma who developed brain metastases (BM) to evaluate our hypothesis that the use of upfront EGFR-tyrosine kinase inhibitors (TKIs), and deferral of radiation therapy (RT), would result in inferior intracranial progression-free survival but similar overall survival (OS).
  
  
  
  Of 202 patients diagnosed with EGFR-mutant NSCLC between July 1, 2008, and December 31, 2014, 71 developed BM. Twenty-one patients were excluded owing to prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after whole-brain radiation therapy (WBRT)/stereotactic radiosurgery (SRS) or <6 months' follow-up. Of the remaining 50 patients, 17 received upfront EGFR-TKI followed by SRS or WBRT, 17 WBRT then EGFR-TKI, and 16 SRS followed by EGFR-TKI. Disease-specific-graded prognostic assessment was similar among all 3 groups.
  
  
  
  The median OS was longer in the upfront RT group compared with the upfront EGFR-TKI group (34.1 vs 19.4 months; P=.01). On subgroup analysis, the SRS group had longer OS than the upfront EGFR-TKI group (58.4 vs 19.4 months; P=.01), but the WBRT group did not (29.9 vs 19.4 months; P=.09). Intracranial progression-free survival was improved in patients receiving upfront RT compared with those receiving upfront EGFR-TKI (37.9 vs 10.6 months; P<.001).
  
  
  
  The present study suggests that the use of upfront EGFR-TKI, and the deferral of SRS or WBRT, may result in inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. A prospective, multi-institutional, randomized trial of upfront EGFR-TKI with RT at intracranial progression versus upfront RT followed by EGFR-TKI is urgently needed.
authors.affiliation: Department of Radiation Oncology, Yale School of Medicine, New Haven, Connecticut. Electronic address: william.magnuson@yale.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Magnuson
authors.affiliation: Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Jacky T
authors.initials: JT
authors.lastname: Yeung
authors.affiliation: Yale School of Medicine, New Haven, Connecticut.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Guillod
authors.affiliation: Department of Medical Oncology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Scott N
authors.initials: SN
authors.lastname: Gettinger
authors.affiliation: Department of Radiation Oncology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: James B
authors.initials: JB
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Veronica L
authors.initials: VL
authors.lastname: Chiang
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D016371:Cranial Irradiation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016634:Radiosurgery; D012189:Retrospective Studies; D016879:Salvage Therapy
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors