Hypothyroidism correlates with favourable survival prognosis in patients with brain metastatic cancer.


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
08 2020
Historique:
received: 23 02 2020
revised: 29 04 2020
accepted: 10 05 2020
pubmed: 1 7 2020
medline: 31 12 2020
entrez: 1 7 2020
Statut: ppublish

Résumé

Several preclinical and epidemiologic studies have indicated tumour-promoting effects of thyroid hormones (THs). However, very limited knowledge exists on the prognostic impact of thyroid function in metastatic cancer. We compiled a discovery cohort of 1692 patients with newly diagnosed brain metastases (BMs) of solid cancers treated at the Medical University of Vienna and an independent validation cohort of 191 patients with newly diagnosed BMs treated at the University Hospital Zurich. Hypothyroidism before diagnosis of cancer was evident in 133 of 1692 (7.9%) patients of the discovery, and in 18 of 191 (9.4%) patients of the validation cohort. In the discovery cohort, hypothyroidism was statistically significantly associated with favourable survival prognosis from diagnosis of cancer (31 vs. 21 months; p = 0.0026) and with survival prognosis from diagnosis of BMs (12 vs. 7 months; p = 0.0079). In multivariate analysis including the diagnosis-specific graded prognostic assessment score, primary tumour type and sex, hypothyroidism was an independent factor associated with survival after diagnosis of BMs (hazard ratio: 0.76; 95% confidence interval [CI]: (0.63; 0.91; p = 0.0034). In the validation cohort, the association of hypothyroidism and favourable survival prognosis from diagnosis of cancer (55 vs. 11 months; p = 0.00058), as well as from diagnosis of BMs (40 vs. 10 months; p = 0.0036) was confirmed. Pre-existing hypothyroidism was strongly and independently associated with prognosis in patients with newly diagnosed BMs, supporting the evidence from preclinical data that THs may indeed have a tumour-promoting effect. Further investigation of the underlying pathobiological mechanism and potential therapeutic implications are required.

Sections du résumé

BACKGROUND
Several preclinical and epidemiologic studies have indicated tumour-promoting effects of thyroid hormones (THs). However, very limited knowledge exists on the prognostic impact of thyroid function in metastatic cancer.
METHODS
We compiled a discovery cohort of 1692 patients with newly diagnosed brain metastases (BMs) of solid cancers treated at the Medical University of Vienna and an independent validation cohort of 191 patients with newly diagnosed BMs treated at the University Hospital Zurich.
RESULTS
Hypothyroidism before diagnosis of cancer was evident in 133 of 1692 (7.9%) patients of the discovery, and in 18 of 191 (9.4%) patients of the validation cohort. In the discovery cohort, hypothyroidism was statistically significantly associated with favourable survival prognosis from diagnosis of cancer (31 vs. 21 months; p = 0.0026) and with survival prognosis from diagnosis of BMs (12 vs. 7 months; p = 0.0079). In multivariate analysis including the diagnosis-specific graded prognostic assessment score, primary tumour type and sex, hypothyroidism was an independent factor associated with survival after diagnosis of BMs (hazard ratio: 0.76; 95% confidence interval [CI]: (0.63; 0.91; p = 0.0034). In the validation cohort, the association of hypothyroidism and favourable survival prognosis from diagnosis of cancer (55 vs. 11 months; p = 0.00058), as well as from diagnosis of BMs (40 vs. 10 months; p = 0.0036) was confirmed.
CONCLUSION
Pre-existing hypothyroidism was strongly and independently associated with prognosis in patients with newly diagnosed BMs, supporting the evidence from preclinical data that THs may indeed have a tumour-promoting effect. Further investigation of the underlying pathobiological mechanism and potential therapeutic implications are required.

Identifiants

pubmed: 32603949
pii: S0959-8049(20)30277-X
doi: 10.1016/j.ejca.2020.05.011
pii:
doi:

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't Validation Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

150-158

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement A.S.B. has received research support from Daiichi Sankyo (≤10000€), Roche (>10000€); has received honoraria for lectures;has been a member of the consultation or advisory board participation from Roche Bristol-Meyers Squibb, Merck, Daiichi Sankyo (all < 5000€), has received travel support from Roche, Amgen and AbbVie. M.K. has received research support from Sanofi, AstraZeneca and Ipsen; served as a speaker and received consulting fees from AstraZeneca, Novartis, Novo Nordisk, Lilly, Merck, Böhringer, Roche and Sanofi. M.W. has received research grants from Abbvie, Adastra, Bristol Meyer Squibb (BMS), Dracen, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, Piqur and Roche; has received honoraria for lectures or served as a member of advisory board participation or consulting from Abbvie, Basilea, Bristol Meyer Squibb (BMS), Celgene, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, Orbus, Roche and Tocagen. M.P. has received research support from Böhringer-Ingelheim, GlaxoSmithKline, Merck Sharp & Dome and Roche; has received honoraria for lectures; served as a member of the consultation or advisory board participation (all < 5000€) from Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Merck Sharp & Dome. All the other authors have no conflicts of interest to declare.

Auteurs

Anna S Berghoff (AS)

Department of Medicine I, Division of Oncology, Medical University of Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Austria.

Christoph Wippel (C)

Department of Medicine I, Division of Oncology, Medical University of Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Austria.

Angelika M Starzer (AM)

Department of Medicine I, Division of Oncology, Medical University of Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Austria.

Nicolas Ballarini (N)

Section for Medical Statistics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Austria.

Fabian Wolpert (F)

Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland.

Elisabeth Bergen (E)

Department of Medicine I, Division of Oncology, Medical University of Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Austria.

Peter Wolf (P)

Department of Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Austria.

Ariane Steindl (A)

Department of Medicine I, Division of Oncology, Medical University of Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Austria.

Georg Widhalm (G)

Comprehensive Cancer Center, Medical University of Vienna, Austria; Department of Neurosurgery, Medical University of Vienna, Austria.

Brigitte Gatterbauer (B)

Comprehensive Cancer Center, Medical University of Vienna, Austria; Department of Neurosurgery, Medical University of Vienna, Austria.

Christine Marosi (C)

Department of Medicine I, Division of Oncology, Medical University of Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Austria.

Karin Dieckmann (K)

Comprehensive Cancer Center, Medical University of Vienna, Austria; Department of Radiotherapy, Medical University of Vienna, Austria.

Rupert Bartsch (R)

Department of Medicine I, Division of Oncology, Medical University of Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Austria.

Thomas Scherer (T)

Department of Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Austria.

Franz Koenig (F)

Section for Medical Statistics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Austria.

Michael Krebs (M)

Department of Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Austria.

Michael Weller (M)

Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland.

Matthias Preusser (M)

Department of Medicine I, Division of Oncology, Medical University of Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Austria. Electronic address: Matthias.Preusser@meduniwien.ac.at.

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