title: Hypothyroidism as a predictive clinical marker of better treatment response to sunitinib therapy.
abstract: BACKGROUND
  Tyrosine kinase inhibitors are standard treatment in patients with metastatic renal cell carcinoma (mRCC). Several studies have indicated that side-effects including hypothyroidism may serve as potential predictive biomarkers of treatment efficacy.
  
  
  METHODS
  All patients with clear cell mRCC treated with sunitinib in the first-line setting in our Center between November 2008 and October 2013 were included. Thyroid function was assessed after every 2 cycles. Prognostic factors were tested using Cox proportional hazards model for univariate analysis.
  
  
  RESULTS
  During treatment, 29.3% developed hypothyroidism, with a median of peak TSH values of 34.4 mIU/L. Patients who had both TSH >4 mIU/L and were receiving substitution therapy with levothyroxine had prolonged PFS compared to all other patients (25.3 months vs. 9.0 months; p=0.042).
  
  
  CONCLUSIONS
  The rate of hypothyroidism as a side-effect of sunitinib in patients with mRCC is significant. Patients with symptomatic hypothyroidism experienced significantly longer PFS, but without difference in OS.
authors.affiliation: Department of Oncology and Nuclear Medicine, University Hospital Centre "Sestre Milosrdnice", Zagreb, Croatia davor.kust@kbcsm.hr.
authors.forename: Davor
authors.initials: D
authors.lastname: Kust
authors.affiliation: Department of Oncology and Nuclear Medicine, University Hospital Centre "Sestre Milosrdnice", Zagreb, Croatia.
authors.forename: Marin
authors.initials: M
authors.lastname: Prpić
authors.affiliation: Department of Oncology and Nuclear Medicine, University Hospital Centre "Sestre Milosrdnice", Zagreb, Croatia.
authors.forename: Jure
authors.initials: J
authors.lastname: Murgić
authors.affiliation: Department of Oncology and Nuclear Medicine, University Hospital Centre "Sestre Milosrdnice", Zagreb, Croatia.
authors.forename: Marijana
authors.initials: M
authors.lastname: Jazvić
authors.affiliation: Department of Oncology and Nuclear Medicine, University Hospital Centre "Sestre Milosrdnice", Zagreb, Croatia.
authors.forename: Blanka
authors.initials: B
authors.lastname: Jakšić
authors.affiliation: Department of Oncology and Nuclear Medicine, University Hospital Centre "Sestre Milosrdnice", Zagreb, Croatia.
authors.forename: Dražena
authors.initials: D
authors.lastname: Krilić
authors.affiliation: Department of Oncology and Nuclear Medicine, University Hospital Centre "Sestre Milosrdnice", Zagreb, Croatia.
authors.forename: Ante
authors.initials: A
authors.lastname: Bolanča
authors.affiliation: Department of Oncology and Nuclear Medicine, University Hospital Centre "Sestre Milosrdnice", Zagreb, Croatia.
authors.forename: Zvonko
authors.initials: Z
authors.lastname: Kusić
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced / Q000175:diagnosis*; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Clinical markers; hypothyroidism; levothyroxine substitution therapy; predictive factor; renal cell carcinoma; sunitinib