title: A five-factor biomarker profile obtained week 4-12 of treatment for improved prognostication in metastatic renal cell carcinoma: Results from DARENCA study 2.
abstract: BACKGROUND
  Several biomarkers of treatment efficacy have been associated with a better prognosis in patients with metastatic renal cell carcinoma (mRCC). The prognostic significance of biomarkers in the early treatment phase is unclear.
  
  
  METHODS
  In a complete national cohort of mRCC patients receiving first-line tyrosine kinase inhibitors (TKI) or interleukin-2 based immunotherapy (IT) from 2006 to 2010, overall survival (OS) was analysed for baseline International mRCC Database Consortium (IMDC) classification factors and on-treatment time-dependent biomarkers obtained day 1 each cycle week 4-12 after treatment initiation with multivariate analysis and bootstrap validation.
  
  
  RESULTS
  A total of 735 patients received first-line TKI (59%) or IT (41%). Median OS was overall 14.0 months and 33.4, 18.5, and 5.8 months for baseline IMDC favourable, intermediate, and poor risk groups, respectively (p < 0.0001). Systolic blood pressure ≥140 mmHg, neutrophils < lower level of normal (LLN), platelets < LLN, sodium ≥ LLN, and LDH ≤1.5 times upper level of normal after treatment initiation were significantly associated with favourable OS independent of baseline IMDC risk group in multivariate analyses stratified for TKI and IT (p ≤ 0.04). Concordance (C)-index for IMDC classification alone was 0.625 (95% CI 0.59-0.66) and combined with the five-factor biomarker profile 0.683 (95% CI 0.64-0.72). For patients with good (3-5 factors) and poor (0-2 factors) biomarker profile median OS were 23.5 and 9.6 months, respectively (p < 0.0001). Adding the five-factor biomarker profile significantly improved prognostication in IMDC intermediate (25.7 vs. 12.0 months, p < 0.0001) and poor (12.8 vs. 6.4 months, p < 0.0001) risk groups. A trend was seen in IMDC favourable risk group (38.9 vs. 28.7 months, p = 0.112).
  
  
  CONCLUSIONS
  On-treatment hypertension, neutropenia, thrombocytopenia, LDH below 1.5 times upper level of normal, and normal sodium, obtained week 4-12 of treatment, are independent biomarkers of favourable outcome in mRCC, independent of treatment type.
authors.affiliation: a Department of Oncology , Herlev Hospital, University of Copenhagen , Herlev , Denmark .
authors.forename: Anne V
authors.initials: AV
authors.lastname: Soerensen
authors.affiliation: a Department of Oncology , Herlev Hospital, University of Copenhagen , Herlev , Denmark .
authors.forename: Poul F
authors.initials: PF
authors.lastname: Geertsen
authors.affiliation: b The Finsen Laboratory , Rigshospitalet and Biotech Research and Innovation Centre (BRIC), University of Copenhagen , Copenhagen , Denmark .
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.affiliation: c Department of Urology , Rigshospitalet, University of Copenhagen , Copenhagen , Denmark .
authors.forename: Gregers G
authors.initials: GG
authors.lastname: Hermann
authors.affiliation: d Department of Oncology , Odense University Hospital , Odense , Denmark .
authors.forename: Niels V
authors.initials: NV
authors.lastname: Jensen
authors.affiliation: e Department of Oncology , Aarhus University Hospital , Aarhus , Denmark .
authors.forename: Kirsten
authors.initials: K
authors.lastname: Fode
authors.affiliation: f Department of Pathology , Aalborg University Hospital , Aalborg , Denmark , and.
authors.forename: Astrid
authors.initials: A
authors.lastname: Petersen
authors.affiliation: g Pfizer Oncology , Sollentuna , Sweden.
authors.forename: Rickard
authors.initials: R
authors.lastname: Sandin
authors.affiliation: e Department of Oncology , Aarhus University Hospital , Aarhus , Denmark .
authors.forename: Frede
authors.initials: F
authors.lastname: Donskov
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor