title: Prognostic factors of survival for patients with metastatic renal cell carcinoma with brain metastases treated with targeted therapy: results from the international metastatic renal cell carcinoma database consortium.
abstract: BACKGROUND
  The outcomes and prognosis of patients with brain metastases from advanced renal cell carcinoma (RCC) are not well characterized in the targeted-therapy era.
  
  
  METHODS
  Data from patients with metastatic RCC (mRCC) and brain metastases treated with targeted therapy were collected through the International Metastatic Renal Cell Carcinoma Database Consortium from 7 cancer centers.
  
  
  RESULTS
  Overall, 106 (15%) of 705 patients with mRCC had brain metastases. Forty-seven patients had brain metastases at the start of first-line anti-vascular endothelial growth factor therapy, and the rest developed metastases during follow-up. Of the patients with brain metastases, 12%, 42% and 29% were in the favorable, intermediate, and poor prognosis groups, respectively, per the Heng criteria. Ninety percent had cerebral metastases, 17% had cerebellar metastases, 37% had a Karnofsky performance status (KPS) <80%, and 80% had neurologic symptoms at presentation. The median largest size and number of brain metastases was 1.8 cm (range, 0.2-6.6 cm) and one (range, 1 to innumerable), respectively. The patients were treated with sunitinib (n = 77), sorafenib (n = 23), bevacizumab (n = 5), and temsirolimus (n = 1). Local disease treatment included whole brain radiotherapy (81%), stereotactic radiosurgery (25%), and neurosurgery (25%). On multivariable analysis, KPS < 80%, diagnosis to treatment with targeted therapy <1 year, and a higher number of brain metastases (>4) was associated with worse survival from the time of diagnosis with brain metastases.
  
  
  CONCLUSIONS
  Patients with brain metastases from RCC are unlikely to be in the favorable risk group. KPS at the start of therapy, diagnosis to treatment time, and the number of brain metastases are prognostic factors for overall survival.
authors.affiliation: Department of Oncology, Tom Baker Cancer Centre, 1331 29th Street NW, Calgary, Alberta, Canada. michael.vickers@albertahealthservices.ca
authors.forename: Michael M
authors.initials: MM
authors.lastname: Vickers
authors.forename: Hulayel
authors.initials: H
authors.lastname: Al-Harbi
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.forename: Scott
authors.initials: S
authors.lastname: North
authors.forename: Mary
authors.initials: M
authors.lastname: MacKenzie
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality*; D016208:Databases, Factual; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000401:mortality*; D058990:Molecular Targeted Therapy; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077157:Sorafenib; D000077210:Sunitinib; D013534:Survival; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D009536:Niacinamide; D000068258:Bevacizumab; C401859:temsirolimus; D000077157:Sorafenib; D000077210:Sunitinib; D020123:Sirolimus
keywords: Brain metastases; Mammalian targets of rapamycin; Renal cell carcinoma; Targeted therapy; Vascular endothelial growth factor