Xiao Min, Qian Lan Liu, Zhao Qiu, Ma Jian, Li Qianxiao, Liu Qian, Bi Zhiyan
Department of Oncology, Changzhou Tumor Hospital, Changzhou, Jiangsu 213302, P.R. China.
Department of Education and Teaching, Changzhou No. 2 People's Hospital, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu 213300, P.R. China.
Oncol Lett. 2025 May 26;30(1):364. doi: 10.3892/ol.2025.15110. eCollection 2025 Jul.
Immune-related thyroid dysfunction (irTD) has been associated with clinical outcomes in non-endocrine tumors. However, the association between irTD and therapeutic efficacy or prognosis in gastric cancer remains unclear. The present study retrospectively investigated the occurrence of irTD during immunotherapy for gastric cancer and analyzed its association with clinical efficacy and patient prognosis. A total of 106 patients with advanced gastric cancer, treated with either first-line or second-line programmed cell death protein 1 (PD-1) monoclonal antibody (MAB) in combination with chemotherapy between January 2019 and December 2022 at the Department of Oncology of Changzhou Tumor Hospital (Changzhou, China), were included. Thyroid hormone levels, including thyroid-stimulating hormone, free thyroxine, free triiodothyronine and thyroid peroxidase (TPO), were determined before and after treatment using the electroluminescence method. The changes in the levels of thyroid hormones based on various clinical characteristics were evaluated in relation to the treatment outcomes, including progression-free survival (PFS) and overall survival (OS), in response to PD-1 MAB therapy. No significant associations were detected between the thyroid hormone levels and different clinical characteristics. Among the patients receiving first-line treatment, 40.6% developed irTD and 49.3% experienced TPO abnormalities. Patients with irTD demonstrated a significantly longer median PFS time than those without irTD (312.0±47.6 vs. 222.0±14.7 days; P=0.040), although no significant difference was noted in the median OS time. Similarly, patients with TPO abnormalities exhibited a longer median PFS time when compared to those without abnormalities (312.0±52.5 vs. 222.0±13.6 days; P=0.006), yet no significant difference was noted in the median OS time. In the second-line treatment, the incidence of irTD was 45.9, and 59.5% of the patients showed TPO abnormalities. Although there were no statistically significant differences in the median PFS or OS times between patients without or with irTD or TPO abnormalities, a trend toward longer PFS and OS was recorded in patients with TPO abnormalities. In conclusion, the occurrence of irTD and TPO abnormalities is associated with better efficacy and prolonged survival in patients with gastric cancer undergoing immunotherapy. These thyroid-related changes may serve as valuable biomarkers for predicting the response to PD-1 MAB therapy in this patient population.
免疫相关甲状腺功能障碍（irTD）已与非内分泌肿瘤的临床结局相关。然而，irTD与胃癌治疗疗效或预后之间的关联仍不明确。本研究回顾性调查了胃癌免疫治疗期间irTD的发生情况，并分析了其与临床疗效和患者预后的关联。纳入了2019年1月至2022年12月期间在常州市肿瘤医院（中国常州）肿瘤科接受一线或二线程序性细胞死亡蛋白1（PD-1）单克隆抗体（MAB）联合化疗的106例晚期胃癌患者。采用电化学发光法测定治疗前后的甲状腺激素水平，包括促甲状腺激素、游离甲状腺素、游离三碘甲状腺原氨酸和甲状腺过氧化物酶（TPO）。根据各种临床特征评估甲状腺激素水平变化与PD-1 MAB治疗反应的治疗结局（包括无进展生存期（PFS）和总生存期（OS））之间的关系。未检测到甲状腺激素水平与不同临床特征之间存在显著关联。在接受一线治疗的患者中，40.6%发生了irTD，49.3%出现了TPO异常。与未发生irTD的患者相比，发生irTD的患者中位PFS时间显著更长（312.0±47.6天对222.0±14.7天；P=0.040），尽管中位OS时间未观察到显著差异。同样，与无TPO异常的患者相比，TPO异常的患者中位PFS时间更长（312.0±52.5天对222.0±13.6天；P=0.006），但中位OS时间也未观察到显著差异。在二线治疗中，irTD的发生率为45.9%，59.5%的患者出现TPO异常。尽管无irTD或TPO异常的患者与有irTD或TPO异常的患者之间的中位PFS或OS时间无统计学显著差异，但TPO异常的患者记录到PFS和OS有延长趋势。总之，irTD和TPO异常的发生与接受免疫治疗的胃癌患者更好的疗效和更长的生存期相关。这些甲状腺相关变化可能作为预测该患者群体对PD-1 MAB治疗反应的有价值生物标志物。
