title: Validation of serum amyloid α as an independent biomarker for progression-free and overall survival in metastatic renal cell cancer patients.
abstract: BACKGROUND
  We recently identified apolipoprotein A2 (ApoA2) and serum amyloid α (SAA) as independent prognosticators in metastatic renal cell carcinoma (mRCC) patients, thereby improving the accuracy of the Memorial-Sloan Kettering Cancer Center (MSKCC) model.
  
  
  OBJECTIVE
  Validate these results prospectively in a separate cohort of mRCC patients treated with tyrosine kinase inhibitors (TKIs).
  
  
  METHODS
  For training we used 114 interferon-treated mRCC patients (inclusion 2001-2006). For validation we studied 151 TKI-treated mRCC patients (inclusion 2003-2009).
  
  
  METHODS
  Using Cox proportional hazards regression analysis, SAA and ApoA2 were associated with progression-free survival (PFS) and overall survival (OS). In 72 TKI-treated patients, SAA levels were analyzed longitudinally as a potential early marker for treatment effect.
  
  
  CONCLUSIONS
  Baseline ApoA2 and SAA levels significantly predicted PFS and OS in the training and validation cohorts. Multivariate analysis identified SAA in both separate patient sets as a robust and independent prognosticator for PFS and OS. In contrast to our previous findings, ApoA2 interacted with SAA in the validation cohort and did not contribute to a better predictive accuracy than SAA alone and was therefore excluded from further analysis. According to the tertiles of SAA levels, patients were categorized in three risk groups, demonstrating accurate risk prognostication. SAA as a single biomarker showed equal prognostic accuracy when compared with the multifactorial MSKCC risk mode. Using receiver operating characteristic analysis, SAA levels >71 ng/ml were designated as the optimal cut-off value in the training cohort, which was confirmed for its significant sensitivity and specificity in the validation cohort. Applying SAA >71 ng/ml as an additional risk factor significantly improved the predictive accuracy of the MSKCC model in both independent cohorts. Changes in SAA levels after 6-8 wk of TKI treatment had no value in predicting treatment outcome.
  
  
  CONCLUSIONS
  SAA but not ApoA2 was shown to be a robust and independent prognosticator for PFS and OS in mRCC patients. When incorporated in the MSKCC model, SAA showed additional prognostic value for patient management.
authors.affiliation: Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Joost S
authors.initials: JS
authors.lastname: Vermaat
authors.forename: Frank L
authors.initials: FL
authors.lastname: Gerritse
authors.forename: Astrid A
authors.initials: AA
authors.lastname: van der Veldt
authors.forename: Wijnand M
authors.initials: WM
authors.lastname: Roessingh
authors.forename: Tatjana M
authors.initials: TM
authors.lastname: Niers
authors.forename: Sjoukje F
authors.initials: SF
authors.lastname: Oosting
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
authors.forename: Jeanine M
authors.initials: JM
authors.lastname: Roodhart
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: Jan H
authors.initials: JH
authors.lastname: Schellens
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
authors.forename: Epie
authors.initials: E
authors.lastname: Boven
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Richel
authors.forename: John B
authors.initials: JB
authors.lastname: Haanen
authors.forename: Emile E
authors.initials: EE
authors.lastname: Voest
mesh_terms: D000368:Aged; D016633:Apolipoprotein A-II / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D002423:Cause of Death; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012372:ROC Curve; D000685:Serum Amyloid A Protein / Q000032:analysis*; D016896:Treatment Outcome
chemical_list: C115794:APOA2 protein, human; D016633:Apolipoprotein A-II; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D000685:Serum Amyloid A Protein; D007372:Interferons