title: Safety and efficacy of targeted therapy for renal cell carcinoma with brain metastasis.
abstract: BACKGROUND
  Brain metastases are associated with a poor prognosis in patients with renal cell carcinoma (RCC). The role of targeted therapy in this setting is not well established. The primary objective was to assess overall survival (OS) and neurologic events in patients with brain metastasis treated with targeted agents.
  
  
  METHODS
  Patients with RCC treated with targeted agents for brain metastasis between 2002 and 2012 were retrospectively identified. Kaplan-Meier methodology and a Cox proportional hazards model were used to analyze the association between clinical features and OS.
  
  
  RESULTS
  Of 65 patients identified, 52 (80%) were treated with antiangiogenic agents and 13 (20%) received inhibitors of mTOR (mechanistic target of rapamycin [serine/threonine kinase]); 57 (88%) had local therapy for brain metastasis, including surgery in 3 (5%), radiation therapy in 36 (55%), and both surgery and radiotherapy in 18 (28%). Median follow-up was 12.3 months (1.1-58.8). Median treatment duration for targeted therapy as first-line therapy was 3.4 months (0.3-31.9). The median OS was 12.2 months (95% CI, 8.0-15.5). The risk group according to the Memorial Sloan Kettering Cancer Center (MSKCC) stratification (P = .001), the histology subtype (clear vs. other) (P < .0001), and the number of brain lesions (1 vs. ≥ 2) (P = .004) correlated with OS on multivariate analysis. Neurologic complications were identified in 5 patients (8%), including 2 with radiation necrosis and 3 with brain metastasis hemorrhage.
  
  
  CONCLUSIONS
  The use of targeted agents in the multimodal treatment of patients with RCC and brain metastasis was not associated with excessive neurologic adverse events. Clear cell histology, favorable MSKCC risk status, and solitary brain metastasis are associated with more favorable OS.
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Diogo A
authors.initials: DA
authors.lastname: Bastos
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: molinaa@mskcc.org.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Molina
authors.affiliation: Neuroradiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Vaios
authors.initials: V
authors.lastname: Hatzoglou
authors.affiliation: Biostatistics Service, Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Jia
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Susanne
authors.initials: S
authors.lastname: Velasco
authors.affiliation: Biostatistics Service, Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Voss
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Feldman
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000556:secondary* / Q000601:surgery; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000009:adverse effects* / Q000379:methods*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors
keywords: CNS metastasis; Kidney cancer; Survival; anti-VEGF; mTOR inhibitors