title: Prognostic Significance of Increases in Hemoglobin in Renal Cell Carcinoma Patients During Treatment With VEGF-directed Therapy.
abstract: Increases in hemoglobin have been reported in renal cell carcinoma (RCC) patients treated with vascular endothelial growth factor (VEGF) pathway-targeted therapies and have been associated with increased progression-free survival (PFS). We retrospectively evaluated its significance as a predictive biomarker of clinical response in RCC.
  
  
  
  Patients with advanced RCC treated with VEGF receptor tyrosine kinase inhibitors (TKIs) or bevacizumab as a first-line therapy were identified. Hemoglobin levels were retrieved at baseline and then at monthly intervals for 6 months. Absolute and percentage increases over baseline were evaluated as predictors of objective response rate, PFS, time to treatment failure, and overall survival. Cox regression was used to estimate change status hazard ratios (HR) in univariate and multivariable models.
  
  
  
  Among the 71 eligible patients, elevations in hemoglobin were observed in 83%, with a median time to increase of 2.4 weeks since treatment initiation. Changes in hemoglobin at time of response were not associated with objective response rate. Landmark analysis at 3 months showed that increases in hemoglobin were associated with worse PFS (8.0 vs. 19.4 months; HR = 2.29; 95% confidence interval, 1.01-5.16; P = .05) and time to treatment failure (6.4 vs. 18.1 months; HR = 2.14; 95% confidence interval, 0.99-4.60, P = .05). Patients with greater increases (15% or more) had significantly shorter PFS (5.5 vs. 13.6 months) and overall survival (20.8 vs. 30.4 months) compared to those with lesser degree of elevations.
  
  
  
  Contrary to prior reports, elevation in hemoglobin on VEGF-directed therapy was associated with worse clinical outcomes, and the greater the degree of elevation, the poorer the prognosis.
authors.affiliation: Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Tripathi
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Susanna
authors.initials: S
authors.lastname: Jacobus
authors.affiliation: Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Hope
authors.initials: H
authors.lastname: Feldman
authors.affiliation: Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA. Electronic address: laurenc_harshman@dfci.harvard.edu.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Harshman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000068258:Bevacizumab / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D006454:Hemoglobins; D047428:Protein Kinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: Bevacizumab; Erythrocytosis; Polycythemia; VEGF inhibition; VEGFR TKI