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

In 2 distinct series of patients with metastatic colorectal cancer treated with regorafenib, we demonstrated an independent association between higher baseline free triiodothyronine/free thyroxine ratio and better overall survival. Future studies aimed to better clarify details on reduced peripheral conversion of thyroid hormone are warranted to understand whether free triiodothyronine/free thyroxine ratio is a marker of progression or a metabolic alteration with potential therapeutic implications. 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. (C) 2018 Elsevier Inc. All rights reserved.