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

      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

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      References

        • St Germain D.L.
        • Galton V.A.
        • Hernandez A.
        Minireview: defining the roles of the iodothyronine deiodinases: current concepts and challenges.
        Endocrinology. 2009; 150: 1097-1107
        • Boron W.F.
        • Boulpaep E.L.
        Medical Physiology.
        2nd ed. Elsevier, New York2012
        • Lamprou V.
        • Varvarousis D.
        • Polytarchou K.
        • Varvarousi G.
        • Xanthos T.
        The role of thyroid hormones in acute coronary syndromes: prognostic value of alterations in thyroid hormones.
        Clin Cardiol. 2017; 40: 528-533
        • Fragidis S.
        • Sombolos K.
        • Thodis E.
        • et al.
        Low T3 syndrome and long-term mortality in chronic hemodialysis patients.
        World J Nephrol. 2015; 4: 415-422
        • Economidou F.
        • Douka E.
        • Tzanela M.
        • Nanas S.
        • Kotanidou A.
        Thyroid function during critical illness.
        Hormones (Athens). 2011; 10: 117-124
        • Bertoli A.
        • Valentini A.
        • Cianfarani M.A.
        • Gasbarra E.
        • Tarantino U.
        • Federici M.
        Low FT3: a possible marker of frailty in the elderly.
        Clin Interv Aging. 2017; 12: 335-341
        • De Alfieri W.
        • Nistico F.
        • Borgogni T.
        • et al.
        Thyroid hormones as predictors of short- and long-term mortality in very old hospitalized patients.
        J Gerontol A Biol Sci Med Sci. 2013; 68: 1122-1128
        • van den Beld A.W.
        • Visser T.J.
        • Feelders R.A.
        • Grobbee D.E.
        • Lamberts S.W.
        Thyroid hormone concentrations, disease, physical function, and mortality in elderly men.
        J Clin Endocrinol Metab. 2005; 90: 6403-6409
        • Maia A.L.
        • Goemann I.M.
        • Meyer E.L.
        • Wajner S.M.
        Deiodinases: the balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease.
        J Endocrinol. 2011; 209: 283-297
        • Pasqualetti G.
        • Calsolaro V.
        • Bernardini S.
        • Linsalata G.
        • Bigazzi R.
        • Caraccio N.
        • Monzani F.
        Degree of peripheral thyroxin deiodination, frailty, and long-term survival in hospitalized older patients.
        J Clin Endocrinol Metab. 2018; 103: 1867-1876
        • Yasar Z.A.
        • Kirakli C.
        • Yilmaz U.
        • Ucar Z.Z.
        • Talay F.
        Can non-thyroid illness syndrome predict mortality in lung cancer patients? A prospective cohort study.
        Horm Cancer. 2014; 5: 240-246
        • Gao R.
        • Liang J.H.
        • Wang L.
        • et al.
        Low T3 syndrome is a strong prognostic predictor in diffuse large B cell lymphoma.
        Br J Haematol. 2017; 177: 95-105
        • Pinter M.
        • Haupt L.
        • Hucke F.
        • et al.
        The impact of thyroid hormones on patients with hepatocellular carcinoma.
        PLoS One. 2017; 12: e0181878
        • Shyh-Chang N.
        Metabolic changes during cancer cachexia pathogenesis.
        Adv Exp Med Biol. 2017; 1026: 233-249
        • Grothey A.
        • Van Cutsem E.
        • Sobrero A.
        • et al.
        Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial.
        Lancet. 2013; 381: 303-312
        • Schoenfeld D.A.
        Sample-size formula for the proportional-hazards regression model.
        Biometrics. 1983; 39: 499-503
        • De Groot L.J.
        Non-thyroidal illness syndrome is a manifestation of hypothalamic-pituitary dysfunction, and in view of current evidence, should be treated with appropriate replacement therapies.
        Crit Care Clin. 2006; 22 (vi): 57-86
        • Tognini S.
        • Marchini F.
        • Dardano A.
        • et al.
        Non-thyroidal illness syndrome and short-term survival in a hospitalised older population.
        Age Ageing. 2010; 39: 46-50
        • Bloise F.F.
        • Cordeiro A.
        • Ortiga-Carvalho T.M.
        Role of thyroid hormone in skeletal muscle physiology.
        J Endocrinol. 2018; 236: R57-R68
        • Grothey A.
        • George S.
        • van Cutsem E.
        • Blay J.Y.
        • Sobrero A.
        • Demetri G.D.
        Optimizing treatment outcomes with regorafenib: personalized dosing and other strategies to support patient care.
        Oncologist. 2014; 19: 669-680
        • Giampieri R.
        • Prete M.D.
        • Prochilo T.
        • et al.
        Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: the TRIBUTE analysis.
        Sci Rep. 2017; 7: 45703
        • Pani F.
        • Massidda M.
        • Pusceddu V.
        • et al.
        Regorafenib-induced hypothyroidism and cancer-related fatigue: is there a potential link?.
        Eur J Endocrinol. 2017; 177: 85-92
        • Buda-Nowak A.
        • Kucharz J.
        • Dumnicka P.
        • et al.
        Sunitinib-induced hypothyroidism predicts progression-free survival in metastatic renal cell carcinoma patients.
        Med Oncol. 2017; 34: 68
        • Schmidinger M.
        • Vogl U.M.
        • Bojic M.
        • et al.
        Hypothyroidism in patients with renal cell carcinoma: blessing or curse?.
        Cancer. 2011; 117: 534-544