title: Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma.
abstract: BACKGROUND
  Adult "translocation" renal cell carcinoma (RCC), bearing transcription factor E3 (TFE3) gene fusions at Xp11.2, is a recently recognized, unique entity for which prognosis and therapy remain poorly understood. In the current study, the authors investigated the effect of vascular endothelial growth factor (VEGF)-targeted therapy in this distinct subtype of RCC.
  
  
  METHODS
  A retrospective review was conducted to describe the clinical characteristics and outcome of adult patients with metastatic Xp11.2 RCC who had strong TFE3 nuclear immunostaining and received anti-VEGF therapy. Tumor response to anti-VEGF therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions.
  
  
  RESULTS
  Fifteen patients were identified, of whom 10, 3, and 2 received sunitinib, sorafenib, and monoclonal anti-VEGF antibodies, respectively. The median follow-up was 19.1 months, the median age of the patients was 41 years, and the female:male ratio was 4:1. Initial histologic description included clear cell (n = 8 patients), papillary (n = 1 patient), or mixed clear cell/papillary RCC (n = 6 patients). Five patients had received prior systemic therapy. Five patients had undergone fluorescent in situ hybridization analysis and all demonstrated a translocation involving chromosome Xp11.2. When treated with VEGF-targeted therapy, 3 patients achieved a partial response, 7 patients had stable disease, and 5 patients developed progressive disease. The median PFS and OS of the entire cohort were 7.1 months and 14.3 months, respectively.
  
  
  CONCLUSIONS
  Adult-onset, translocation-associated metastatic RCC is an aggressive disease that affects a younger population of patients with a female predominance. In the current study, VEGF-targeted agents appeared to demonstrate some efficacy.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA. Toni_Choueiri@dfci.harvard.edu
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Zita Dubauskas
authors.initials: ZD
authors.lastname: Lim
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Hirsch
authors.forename: Pheroze
authors.initials: P
authors.lastname: Tamboli
authors.forename: Eric
authors.initials: E
authors.lastname: Jonasch
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
authors.forename: Paola
authors.initials: P
authors.lastname: Dal Cin
authors.forename: Paul
authors.initials: P
authors.lastname: Corn
authors.forename: Ulka
authors.initials: U
authors.lastname: Vaishampayan
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
authors.forename: Nizar M
authors.initials: NM
authors.lastname: Tannir
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D041321:Chromosomes, Human, X; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D014178:Translocation, Genetic; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D007211:Indoles; D011758:Pyrroles; C069203:TFE3 protein, human; D042461:Vascular Endothelial Growth Factor A; D000077210:Sunitinib