title: Correlation of degree of hypothyroidism with survival outcomes in patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors.
abstract: BACKGROUND
  Hypothyroidism is a common adverse effect of vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy in patients with metastatic renal cell carcinoma (mRCC). Some studies have shown an association with improved survival. However, hypothyroidism severity has not been correlated with survival outcomes. We report the incidence and severity of VEGFR-TKI therapy-associated hypothyroidism in correlation with the survival outcomes of patients with mRCC.
  
  
  METHODS
  A retrospective analysis of patients with mRCC who received VEGFR-TKIs (2004 through 2013) was conducted from a single institutional database. Hypothyroidism, progression-free survival (PFS), and overall survival (OS) were assessed. Univariate and multivariate analyses were performed using the Kaplan-Meier method and Cox proportional hazard models.
  
  
  RESULTS
  Of 125 patients with mRCC, 65 were eligible. Their median age was 59 years (range, 45-79 years), and 46 (70.8%) were male. Hypothyroidism occurred in 25 patients (38.5%), of whom 13 had a peak thyroid-stimulating hormone (TSH) level > 10 mIU/L during treatment. The median OS was significantly longer in patients with a peak TSH > 10 mIU/L than in patients with a peak TSH of ≤ 10 mIU/L (not reached vs. 21.4 months, P = .005). On multivariate analysis, risk criteria, number of previous therapies, and severe hypothyroidism (TSH > 10 mIU/L) during VEGFR-TKI therapy remained significant for improvements in PFS and OS.
  
  
  CONCLUSIONS
  The severity of VEGFR-TKI therapy-associated hypothyroidism (TSH > 10 mIU/L) was associated with improved survival outcomes in patients with mRCC and should not necessitate a dose reduction or therapy discontinuation.
authors.affiliation: University of Utah, Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Erin B
authors.initials: EB
authors.lastname: Bailey
authors.affiliation: University of Utah, Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Srinivas K
authors.initials: SK
authors.lastname: Tantravahi
authors.affiliation: University of Utah, Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Austin
authors.initials: A
authors.lastname: Poole
authors.affiliation: Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT.
authors.forename: Archana M
authors.initials: AM
authors.lastname: Agarwal
authors.affiliation: University of Utah, Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Alli M
authors.initials: AM
authors.lastname: Straubhar
authors.affiliation: University of Utah, Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Batten
authors.affiliation: University of Utah, Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Shiven B
authors.initials: SB
authors.lastname: Patel
authors.affiliation: University of Utah, Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Chesley E
authors.initials: CE
authors.lastname: Wells
authors.affiliation: Pharmacotherapy Outcomes Research Center, University of Utah College of Pharmacy, Salt Lake City, UT.
authors.forename: David D
authors.initials: DD
authors.lastname: Stenehjem
authors.affiliation: University of Utah, Huntsman Cancer Institute, Salt Lake City, UT. Electronic address: Neeraj.Agarwal@hci.utah.edu.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced / Q000473:pathology*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D047428:Protein Kinase Inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Advanced kidney cancer; Outcomes research; Targeted therapy; Thyroid dysfunction; Treatment-related hypothyroidism