title: The radiogenomic risk score stratifies outcomes in a renal cell cancer phase 2 clinical trial.
abstract: OBJECTIVE
  To characterize a radiogenomic risk score (RRS), a previously defined biomarker, and to evaluate its potential for stratifying radiological progression-free survival (rPFS) in patients with metastatic renal cell carcinoma (mRCC) undergoing pre-surgical treatment with bevacizumab.
  
  
  METHODS
  In this IRB-approved study, prospective imaging analysis of the RRS was performed on phase II clinical trial data of mRCC patients (n = 41) evaluating whether patient stratification according to the RRS resulted in groups more or less likely to have a rPFS to pre-surgical bevacizumab prior to cytoreductive nephrectomy. Survival times of RRS subgroups were analyzed using Kaplan-Meier survival analysis.
  
  
  RESULTS
  The RRS is enriched in diverse molecular processes including drug response, stress response, protein kinase regulation, and signal transduction pathways (P < 0.05). The RRS successfully stratified rPFS to bevacizumab based on pre-treatment computed tomography imaging with a median progression-free survival of 6 versus >25 months (P = 0.005) and overall survival of 25 versus >37 months in the high and low RRS groups (P = 0.03), respectively. Conventional prognostic predictors including the Motzer and Heng criteria were not predictive in this cohort (P > 0.05).
  
  
  CONCLUSIONS
  The RRS stratifies rPFS to bevacizumab in patients from a phase II clinical trial with mRCC undergoing cytoreductive nephrectomy and pre-surgical bevacizumab.
  
  
  CONCLUSIONS
  • The RRS SOMA stratifies patient outcomes in a phase II clinical trial. • RRS stratifies subjects into prognostic groups in a discrete or continuous fashion. • RRS is biologically enriched in diverse processes including drug response programs.
authors.affiliation: Department of Radiological Sciences, University of California-Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
authors.forename: Neema
authors.initials: N
authors.lastname: Jamshidi
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Jonasch
authors.affiliation: Department of Radiological Sciences, University of California-Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.|Department of Radiology, University of California-San Diego, San Diego, CA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Zapala
authors.affiliation: Scottsdale Medical Imaging, Scottsdale, AZ, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Korn
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Brooks
authors.affiliation: Department of Surgical and Perioperative Sciences, Urology and Andrology, Umea Hospital, Umea, Sweden.
authors.forename: Borje
authors.initials: B
authors.lastname: Ljungberg
authors.affiliation: Department of Radiological Sciences, University of California-Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA. michaelkuo@mednet.ucla.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kuo
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods*; D015996:Survival Rate / Q000639:trends; D014057:Tomography, X-Ray Computed / Q000379:methods*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab
keywords: Bevacizumab; Imaging biomarker; Imaging surrogate; Radiogenomics; Renal cell carcinoma