Prognostic Value of Thyroid Hormone Ratios in Patients With Advanced Metastatic Colorectal Cancer Treated With Regorafenib: The TOREADOR Study

Clin Colorectal Cancer. 2018 Sep;17(3):e601-e615. doi: 10.1016/j.clcc.2018.05.013. Epub 2018 Jun 8.

Abstract

Background: The impact of free triiodothyronine (FT3)/free thyroxine (FT4) ratio on survival in hospitalized geriatric patients was recently described. Up today, there are no data regarding the prognostic role of FT3/FT4 ratio in patients with advanced cancer. We evaluated the impact of FT3/FT4 ratio on survival in patients with refractory colorectal cancer (CRC) treated with regorafenib.

Methods: Patients with metastatic CRC treated with regorafenib with available clinical data and baseline measurement of FT3, FT4, and thyroid-stimulating hormone (TSH) were considered eligible. Exploratory analyses included subjects treated at Istituto Oncologico Veneto. A confirmatory analysis was planned based on FT3/FT4 ratio tertile results, and a validation cohort was built on data retrieved from University of Cagliari.

Results: In an exploratory cohort, the median overall survival in patients with low, intermediate, and high FT3/FT4 ratios, according to tertiles' value, was 4.8, 5.0, and 7.6 months, respectively (P = .003). The differences were significant in the multivariate model (hazard ratio, 0.43; 95% confidence interval, 0.28-0.68; P = .0003). Confirmatory results were obtained in a validation cohort, both in univariate (P = .0002) and in multivariate (hazard ratio, 0.56; 95% confidence interval, 0.36-0.88; P = .0118) models.

Conclusions: High baseline FT3/FT4 ratio is strongly associated to better outcome in patients with progressive metastatic CRC treated with regorafenib. Further investigations are ongoing to draw definitive conclusions regarding a potential predictive effect.

Keywords: Deiodination; FT(3)/FT(4); Prognosis; Refractory; Survival.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Female
  • Follow-Up Studies
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Phenylurea Compounds / therapeutic use*
  • Prognosis
  • Progression-Free Survival
  • Prospective Studies
  • Pyridines / therapeutic use*
  • Response Evaluation Criteria in Solid Tumors
  • Survival Analysis
  • Thyroid Function Tests / methods*
  • Thyroxine / blood*
  • Triiodothyronine / blood*

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Pyridines
  • Triiodothyronine
  • regorafenib
  • Thyroxine