Department of Medicine I, Division of Oncology, Medical University of Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Austria.
Section for Medical Statistics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Austria.
Eur J Cancer. 2020 Aug;135:150-158. doi: 10.1016/j.ejca.2020.05.011. Epub 2020 Jun 27.
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.
几项临床前和流行病学研究表明，甲状腺激素（THs）具有促进肿瘤生长的作用。然而，关于甲状腺功能在转移性癌症中的预后影响，我们的了解非常有限。
我们编制了一个由 1692 名新诊断为脑转移瘤（BM）的实体瘤患者组成的发现队列，这些患者在维也纳医科大学接受治疗，以及一个由 191 名新诊断为 BM 的患者组成的独立验证队列，这些患者在苏黎世大学医院接受治疗。
在发现队列的 1692 名患者中，有 133 名（7.9%）和验证队列的 191 名患者中的 18 名（9.4%）在癌症诊断前患有甲状腺功能减退症。在发现队列中，甲状腺功能减退症与从癌症诊断开始的有利生存预后显著相关（31 个月与 21 个月；p=0.0026），与从 BM 诊断开始的生存预后也显著相关（12 个月与 7 个月；p=0.0079）。在包括诊断特异性分级预后评估评分、原发肿瘤类型和性别在内的多变量分析中，甲状腺功能减退症是与 BM 诊断后生存相关的独立因素（风险比：0.76；95%置信区间[CI]：（0.63；0.91；p=0.0034）。在验证队列中，甲状腺功能减退症与从癌症诊断开始的有利生存预后（55 个月与 11 个月；p=0.00058）以及从 BM 诊断开始的有利生存预后（40 个月与 10 个月；p=0.0036）的关联得到了确认。
新诊断为 BM 的患者中，预先存在的甲状腺功能减退症与预后强烈且独立相关，这支持了临床前数据表明 THs 可能确实具有促进肿瘤生长的作用的证据。需要进一步研究潜在的病理生物学机制和潜在的治疗意义。
