title: Acquired Hypothyroidism as a Predictive Marker of Outcome in Patients With Metastatic Renal Cell Carcinoma Treated With Tyrosine Kinase Inhibitors: A Literature-Based Meta-Analysis.
abstract: Hypothyroidism in patients with metastatic renal cell carcinoma (mRCC) during treatment with the tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib is a well-established side effect. Furthermore, the potential role of hypothyroidism as predictive marker of outcome has been studied but with conflicting results. The aim of the present meta-analysis was to assess the predictive value of hypothyroidism for progression-free (PFS) and overall survival (OS) in patients with mRCC during TKI therapy. We searched PubMed and the electronic abstract databases of the major international congresses' proceedings to identify all eligible studies that reported a correlation between the development of hypothyroidism during TKI treatment and outcome in patients with mRCC. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS and OS were obtained from these publications and pooled in a meta-analysis. Eleven studies with a total of 500 patients fulfilled the inclusion criteria. We found no statistical significant difference in PFS between patients who developed hypothyroidism during sunitinib therapy and unaffected patients (HR, 0.82; 95% CI, 0.59-1.13; P = .22; 6 studies; 250 patients). The HR for OS was 0.52 (95% CI, 0.31-0.87; P = .01) for patients who developed hypothyroidism during sunitinib therapy compared with patients who did not (4 studies; 147 patients). The development of hypothyroidism during TKI therapy is not clearly shown to be predictive of efficacy in patients with mRCC. The observed advantage in OS for the patients with acquired hypothyroidism should be interpreted with caution.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden; Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden. Electronic address: anearchou@hotmail.com.
authors.forename: Andreas
authors.initials: A
authors.lastname: Nearchou
authors.affiliation: Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden; Department of Radiology, Oncology and Radiation Science, University of Uppsala, Uppsala, Sweden.
authors.forename: Antonis
authors.initials: A
authors.lastname: Valachis
authors.affiliation: Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden; Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden.
authors.forename: Pehr
authors.initials: P
authors.lastname: Lind
authors.affiliation: Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Akre
authors.affiliation: Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Sandström
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors
keywords: TKI; mRCC; sorafenib; sunitinib; thyroid function