title: Impact of bone and liver metastases on patients with renal cell carcinoma treated with targeted therapy.
abstract: BACKGROUND
  The skeleton and liver are frequently involved sites of metastasis in patients with metastatic renal cell carcinoma (RCC).
  
  
  OBJECTIVE
  To analyze outcomes based on the presence of bone metastases (BMs) and/or liver metastases (LMs) in patients with RCC treated with targeted therapy.
  
  
  METHODS
  We conducted a review from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) of 2027 patients with metastatic RCC.
  
  
  METHODS
  We analyzed the impact of the site of metastasis on overall survival (OS) and time-to-treatment failure. Statistical analyses were performed using multivariable Cox regression.
  
  
  CONCLUSIONS
  The presence of BMs was 34% overall, and when stratified by IMDC risk groups was 27%, 33%, and 43% in the favorable-, intermediate-, and poor-risk groups, respectively (p<0.001). The presence of LMs was 19% overall and higher in the poor-risk patients (23%) compared with the favorable- or intermediate-risk groups (17%) (p=0.003). When patients were classified into four groups based on the presence of BMs and/or LMs, the hazard ratio, adjusted for IMDC risk factors, was 1.4 (95% confidence interval [CI], 1.22-1.62) for BMs, 1.42 (95% CI, 1.17-1.73) for LMs, and 1.82 (95% CI, 1.47-2.26) for both BMs and LMs compared with other metastatic sites (p<0.0001). The prediction model performance for OS was significantly improved when BMs and LMs were added to the IMDC prognostic model (likelihood ratio test p<0.0001). Data in this analysis were collected retrospectively.
  
  
  CONCLUSIONS
  The presence of BMs and LMs in patients treated with targeted agents has a negative impact on survival. Patients with BMs and/or LMs may benefit from earlier inclusion on clinical trials of novel agents or combination-based therapies.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: Rana R
authors: RR
authors: McKay
authors: Department of Oncology, Tom Baker Cancer Center/University of Calgary, Calgary, Canada; Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors: Nils
authors: N
authors: Kroeger
authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: Wanling
authors: W
authors: Xie
authors: Department of Oncology, Asan Medical Center/University of Ulsan College of Medicine, Seoul, South Korea.
authors: Jae-Lyun
authors: JL
authors: Lee
authors: Departments of Hematology and Medical Oncology, Princess Margaret Hospital, Toronto, Canada.
authors: Jennifer J
authors: JJ
authors: Knox
authors: Division of Medical Oncology/Hematology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Canada.
authors: Georg A
authors: GA
authors: Bjarnason
authors: Department of Medical Oncology, London Regional Cancer Program, London, Canada.
authors: Mary J
authors: MJ
authors: MacKenzie
authors: Division of Medical Oncology, Queen Elizabeth II Health Sciences Centre, Halifax, Canada.
authors: Lori
authors: L
authors: Wood
authors: Division of Oncology, Stanford Medical Center, Stanford, CA, USA.
authors: Sandy
authors: S
authors: Srinivas
authors: Division of Hematology/Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA.
authors: Ulka N
authors: UN
authors: Vaishampayan
authors: Division of Medical Oncology, Yonsei Cancer Center/Yonsei University College of Medicine, Seoul, South Korea.
authors: Sun-Young
authors: SY
authors: Rha
authors: Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
authors: Sumanta K
authors: SK
authors: Pal
authors: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors: Frede
authors: F
authors: Donskov
authors: Division of Medical Oncology/Hematology, University of Utah/Huntsman Cancer Institute, Salt Lake City, UT, USA.
authors: Srinivas K
authors: SK
authors: Tantravahi
authors: Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
authors: Brian I
authors: BI
authors: Rini
authors: Department of Oncology, Tom Baker Cancer Center/University of Calgary, Calgary, Canada.
authors: Daniel Y C
authors: DY
authors: Heng
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: toni_choueiri@DFCI.harvard.edu.
authors: Toni K
authors: TK
authors: Choueiri
mesh_terms: D001859:Bone Neoplasms / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D058990:Molecular Targeted Therapy; D012189:Retrospective Studies
keywords: Bone metastases; Liver metastases; Outcome; Renal cell carcinoma; VEGF therapy; mTOR inhibitors
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