title: Treatment options for patients with brain metastases from EGFR/ALK-driven lung cancer.
abstract: Brain metastases in EGFR/ALK-driven NSCLC frequently pose treatment dilemmas. Tyrosine kinase inhibitors (TKIs) can control extracranial disease, but radiotherapy is often required for intracranial control. We aimed to evaluate the impact of first-line whole brain radiotherapy (WBRT), stereotactic radiotherapy (SRS) or TKI alone on outcomes of patients with brain metastases from EGFR/ALK-driven NSCLC.
  
  
  
  This single center retrospective review included 184 patients with brain metastases from EGFR/ALK-driven NSCLC, and analyzed effect of treatment choice on time to intracranial progression (TTIP) and overall survival (OS).
  
  
  
  First-line treatment for brain metastases consisted of WBRT in 120 patients, SRS in 37 and TKI alone in 27. WBRT-treated patients had more brain metastases, and more baseline symptoms. Median TTIP was longer in the WBRT group at 50.5months than SRS or TKI groups at 12 and 15months (p=0.0038). No significant difference was seen in median OS: 21.6months in the WBRT group, 23.9months in the SRS group and 22.6months in the TKI group (p=0.67). In multivariable analysis, age>65years (HR 2.2, p=0.0014), greater number of brain metastases (HR 2.48, p=0.0002) and greater number of extracranial metastatic sites (2 vs 0-1 HR=2.05, p=0.014 and 3+ vs 0-1 HR=2.95, p=0.0001 were associated with shorter OS. No independent effect was seen from first-line CNS treatment choice.
  
  
  
  First-line WBRT for brain metastases from EGFR/ALK-driven NSCLC was associated with longer TTIP than SRS or TKI alone, with no difference in OS. These results could support deferral of WBRT until intracranial progression in selected patients who are closely monitored.
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada. Electronic address: mark.doherty@mail.utoronto.ca.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Doherty
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Grzegorz J
authors.initials: GJ
authors.lastname: Korpanty
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Pascale
authors.initials: P
authors.lastname: Tomasini
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Moein
authors.initials: M
authors.lastname: Alizadeh
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Jao
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Labbé
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Celine M
authors.initials: CM
authors.lastname: Mascaux
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Petra
authors.initials: P
authors.lastname: Martin
authors.affiliation: Laboratory Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.affiliation: Laboratory Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.affiliation: Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Bradbury
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Feld
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Chung
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D001932:Brain Neoplasms / Q000556:secondary* / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D016371:Cranial Irradiation / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016634:Radiosurgery; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK translocation; Brain metastases; EGFR mutation; Non-small cell lung cancer; Stereotactic radiotherapy; Whole brain radiotherapy