Abstract
As endocrinological parameters such as thyroid hormones modulate proliferative, metabolic, and angiogenic pathways, it is surmised that their levels can be associated with cancer development and progression. Most patients with gastroesophageal cancer are diagnosed very late and have a poor prognosis, yet the association with endocrinological parameters has not been addressed so far. The aim of this study was to correlate hormones with the outcome, so new prognostic and potentially therapeutic markers can be defined. We analyzed clinical and endocrinological parameters including history of thyroid disorders and laboratory analyses of thyroid hormones and correlated these with the overall survival in a large European cohort of patients with inoperable locally advanced or metastatic gastroesophageal cancer treated between 2002 and 2018 at the Vienna General Hospital, Austria. In total, the survival outcome of 258 patients was evaluated. Higher levels of fT4 (p = 0.041, HR = 2.202) and lower levels of T3 (p = 0,003, HR = 0,141) were associated with significantly shorter survival. However, the overall survival of patients with known thyroid disorders did not differ significantly from euthyroid patients (euthyroid, 283 days; hyperthyroid, 354 days; hypothyroid, 284 days; p = 0.472). Elevated fT4 levels are associated with poorer overall survival of patients with gastroesophageal cancer in advanced stages. Since data on the correlation of endocrinological parameters and gastroesophageal cancer are scarce, this analysis is an important impulse for further studies concerning the impact of thyroxine on patients with cancer of the upper GI tract.
Highlights
Cancer of the upper gastrointestinal (GI) tract which encompasses esophageal cancer, gastric cancer, as well as cancer of the gastroesophageal junction is a frequent disease and major contributor to global disease burden
The aim of this study was to investigate the prognostic impact of thyroid hormones in a large, well-defined cohort of patients suffering from metastatic gastroesophageal cancer
The association of thyroid function and cancer progression has been addressed by several preclinical and epidemiological studies; to our best knowledge, we are the first to investigate the prognostic impact of thyroid function in a large cohort of patients suffering from metastatic gastroesophageal cancer
Summary
Cancer of the upper gastrointestinal (GI) tract which encompasses esophageal cancer, gastric cancer, as well as cancer of the gastroesophageal junction is a frequent disease and major contributor to global disease burden. Cancer of the upper GI tract is the second leading cause of cancer-related death, with about 1.4 million newly diagnosed cases (951,000 cases of gastric cancer and 456,000 cases of esophageal cancer) in 2012 [1]. Gastroesophageal cancer is usually asymptomatic in early stages, and symptoms such as weight loss, dysphagia, dyspepsia, vomiting, early satiety, and/or iron deficiency anemia develop mostly in advanced tumor stages [2, 3]. For esophageal and gastric cancer, 5year relative survival is 23.6 and 30.6% at locally advanced stages and 4.8 and 5.2% at metastatic stages, respectively [4, 5]. Biological factors, which drive tumor progression and metastasis, are of high clinical interest for the development of new targeted therapeutic approaches in order to potentially prevent or slow down the tumor growth
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