title: Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers.
abstract: BACKGROUND
  Brain metastases (BM) are common in non-small-cell lung cancer (NSCLC). However, the baseline incidence and evolution of BM over time in oncogene-driven NSCLCs are seldom reported. In this study, we evaluated the frequency of BM in patients with epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged NSCLC.
  
  
  METHODS
  The presence of BM, clinicopathologic data, and tumor genotype were retrospectively compiled and analyzed from a cohort of 381 patients.
  
  
  RESULTS
  We identified 86 EGFR-mutated (90.7% with metastatic disease; 85.9% received an EGFR inhibitor) and 23 ALK-rearranged (91.3% with metastatic disease; 85.7% received an ALK inhibitor) NSCLCs. BM were present in 24.4% of EGFR-mutated and 23.8% of ALK-rearranged NSCLCs at the time of diagnosis of advanced disease. This study did not demonstrate a difference in the cumulative incidence of BM over time between the two cohorts (EGFR/ALK cohort competing risk regression [CRR] coefficient of 0.78 [95% CI 0.44-1.39], p=0.41). In still living patients with advanced EGFR-mutated NSCLC, 34.2% had BM at 1 year, 38.4% at 2 years, 46.7% at 3 years, 48.7% at 4 years, and 52.9% at 5 years. In still living patients with advanced ALK-rearranged NSCLC, 23.8% had BM at 1 year, 45.5% at 2 years, and 58.4% at 3 years.
  
  
  CONCLUSIONS
  BM are frequent in advanced EGFR-mutated or ALK-rearranged NSCLCs, with an estimated >45% of patients with CNS involvement by three years of survival with the use of targeted therapies. These data point toward the CNS as an important unmet clinical need in the evolving schema for personalized care in NSCLC.
authors: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Deepa
authors: D
authors: Rangachari
authors: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Norihiro
authors: N
authors: Yamaguchi
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Paul A
authors: PA
authors: VanderLaan
authors: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Erik
authors: E
authors: Folch
authors: Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Anand
authors: A
authors: Mahadevan
authors: Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Scott R
authors: SR
authors: Floyd
authors: Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Erik J
authors: EJ
authors: Uhlmann
authors: Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Eric T
authors: ET
authors: Wong
authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Harvard Medical School, Boston, MA, United States.
authors: Suzanne E
authors: SE
authors: Dahlberg
authors: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Mark S
authors: MS
authors: Huberman
authors: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States. Electronic address: dbcosta@bidmc.harvard.edu.
authors: Daniel B
authors: DB
authors: Costa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D018709:Statistics, Nonparametric
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; Brain metastases; CNS; Central nervous system; EGFR; Lung cancer; Mutation; NSCLC; Rearrangement