PO.PS01.10 · 人群科学
癌症治疗后甲状腺功能减退相关的生存结局
Survival outcomes associated with hypothyroidism following cancer therapies
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：甲状腺功能减退是免疫治疗（免疫检查点抑制剂，ICIs）、化疗（酪氨酸激酶抑制剂，TKIs）和放疗等癌症治疗公认的不良反应。尽管有人提出其可作为治疗反应的指标，但其在不同癌种和治疗方式中的预后意义仍未得到充分探讨。本研究评估了治疗诱导的甲状腺功能减退相关的生存结局。
方法：我们使用密歇根大学2006年至2023年间去标识化的电子健康记录数据开展了一项回顾性队列研究。纳入接受ICIs、TKIs或放疗、既往无甲状腺疾病或恶性肿瘤的成人（≥18岁）。我们根据机构实验室标准或甲状腺激素起始治疗来定义甲状腺功能减退。时间依赖性Cox模型估计了总生存期和癌症特异性生存期的风险比（HRs）及95%置信区间（CIs），并对人口统计学、临床和生活方式因素进行校正。分析按治疗类别和癌症部位进行分层；敏感性分析评估了结果的稳健性。
结果：在9,909名患者（57,772人年；中位随访4.64年）中，2,177名（22.0%）发生了甲状腺功能减退（中位发病时间：5.04个月）。治疗诱导的甲状腺功能减退与改善的总生存期（HR = 0.86 [0.79-0.93]，p < 0.001）和癌症特异性生存期（HR = 0.76 [0.70-0.84]，p < 0.001）相关。分层分析显示，免疫治疗后（总生存期HR = 0.75 [0.61-0.92]，p = 0.01；癌症特异性HR = 0.75 [0.66-0.94]，p = 0.01）和放疗后（HR = 0.88 [0.81-0.96]，p = 0.01；癌症特异性HR = 0.76 [0.68-0.84]，p <0.001）发生甲状腺功能减退具有显著的生存获益，但化疗后则没有。在脑/中枢神经系统（HR = 0.39 [0.26-0.61]，p < 0.001）、唇/口腔/咽部（HR = 0.77 [0.61-0.97]，p = 0.03）和肺/支气管癌（HR = 0.80 [0.66-0.97]，p = 0.03）观察到部位特异性生存获益，但在结肠癌中死亡率更高（HR = 1.82 [1.10-3.02]，p = 0.02）。结果在各敏感性分析中保持一致。
结论：免疫治疗和放疗后的甲状腺功能减退与改善的生存相关，支持其作为治疗获益预后生物标志物的潜力。未来的研究应探讨其潜在机制和临床意义。
查看英文原文 English abstract
Background: Hypothyroidism is a recognized adverse effect of cancer therapies such as immunotherapy (immune checkpoint inhibitors, ICIs), chemotherapy (tyrosine kinase inhibitors, TKIs), and radiotherapy. Although proposed as an indicator of treatment response, its prognostic significance across cancer types and therapies remains under-explored. This study evaluated survival outcomes associated with treatment-induced hypothyroidism.
Methods: We conducted a retrospective cohort study using de-identified electronic health record data from the University of Michigan between 2006 and 2023. Adults (≥18 years) receiving ICIs, TKIs, or radiotherapy, without prior thyroid disease or malignancy were included. We defined hypothyroidism by institutional laboratory criteria or thyroid hormone initiation. Time-dependent Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cancer-specific survival, adjusting for demographic, clinical, and lifestyle factors. Analyses were stratified by treatment class and cancer site; sensitivity analyses assessed robustness.
Results: Among 9,909 patients (57,772 person-years; median follow-up 4.64 years), 2,177 (22.0%) developed hypothyroidism (median onset time: 5.04 months). Treatment-induced hypothyroidism was associated with improved overall (HR = 0.86 [0.79-0.93], p < 0.001) and cancer-specific survival (HR = 0.76 [0.70-0.84], p < 0.001). Stratified analyses showed significant survival benefits with hypothyroidism following immunotherapy (overall HR = 0.75 [0.61-0.92], p = 0.01; cancer-specific HR = 0.75 [0.66-0.94], p = 0.01) and radiotherapy (HR = 0.88 [0.81-0.96], p = 0.01; cancer-specific HR = 0.76 [0.68-0.84], p <0.001), but not for chemotherapy. Site specific survival benefits were observed in brain/CNS (HR = 0.39 [0.26-0.61], p < 0.001), lip/oral cavity/pharyngeal (HR = 0.77 [0.61-0.97], p = 0.03) and lung/bronchus cancers (HR = 0.80 [0.66-0.97], p = 0.03) but higher mortality in colon cancer (HR = 1.82 [1.10-3.02], p = 0.02). Results were consistent across sensitivity analyses.
Conclusion: Hypothyroidism after immunotherapy and radiotherapy was associated with improved survival, supporting its potential as a prognostic biomarker of therapeutic benefit. Future studies should investigate the underlying mechanisms and clinical implications.
利益披露 Disclosure
H. D. Momo, None..
M. R. Haymart, None..
X. Shi, None..
A. M. Mondul, None.