首次 ¹³¹I治疗后早期T淋巴细胞水平预测分化型甲状腺癌全切术后清甲疗效

Predictive value of early T lymphocyte levels after the first ¹³¹I treatment for the efficacy of thyroid ablation in differentiated thyroid cancer

摘要

目的：探究分化型甲状腺癌（DTC）全切术后首次 ¹³¹I治疗后早期T淋巴细胞水平与半年后甲状腺清除（清甲）疗效的关系。方法：选取2021年5月至2024年5月我院收治的100例DTC全切术后行 ¹³¹I治疗的患者作为研究对象。 ¹³¹I治疗24周后根据效果分为疗效满意（ER）、疗效不确切（IDR）、生化疗效不佳（BIR）和结构性疗效不佳（SIR），其中ER和IDR为有效组，BIR和SIR为无效组。重复测量方差分析有效组和无效组患者 ¹³¹I治疗后早期T淋巴细胞水平。广义线性混合模型（GLMMs）分析T淋巴细胞水平与清甲效果的关系。采用亚组分析检验T淋巴细胞水平与清甲疗效关联的稳定性。应用限制性立方样条法分析治疗后8周T淋巴细胞亚群水平与清甲疗效之间的非线性剂量-反应关系。受试者工作特征曲线（ROC）分析预测DTC全切术后半年清甲疗效的效能。结果：（1）与治疗前相比，有效组和无效组患者治疗后的CD3 ⁺、CD4 ⁺、CD4 ⁺/CD8 ⁺均上升（P＜0.05），CD8 ⁺水平下降（P＜0.05）。与无效组相比，有效组不同时间的CD3 ⁺、CD4 ⁺、CD4 ⁺/CD8 ⁺、FT ₃、FT ₄、血钙、iPTH均升高（P＜0.05），CD8 ⁺、TSH均降低（P＜0.05）。（2）GLMMs结果表明，T淋巴细胞水平与 ¹³¹I治疗半年后清甲无效相关（P＜0.001）。（3）亚组分析显示，在血清TSH亚组中，T淋巴细胞水平与清甲疗效的相关性稳定存在，且亚组间不存在明显交互作用（P交互＞0.05）。（4）限制性立方样条法分析显示： ¹³¹I治疗后8周患者T淋巴细胞水平与清甲疗效呈非线性剂量-反应关系（P＜0.05），△CD3 ⁺、△CD4 ⁺、△CD4 ⁺/CD8 ⁺水平与清甲疗效呈正相关，△CD8 ⁺与清甲疗效呈负相关。（5）ROC分析显示，治疗后8周△CD3 ⁺、△CD4 ⁺、△CD8 ⁺、△CD4 ⁺/CD8 ⁺预测清甲疗效的AUC分别为0.64（95%CI：0.32~0.76）、0.77（95%CI：0.46~0.84）、0.75（95%CI：0.50~0.87）、0.85（95%CI：0.67~0.94），截断值分别为58.56、33.23、29.74、1.16。结论：DTC全切术后首次 ¹³¹I治疗早期T淋巴细胞免疫功能变化与半年后清甲疗效显著相关，其中治疗后8周CD4 ⁺/CD8 ⁺变化对预测清甲疗效具有较高价值，可作为潜在的免疫监测指标。

Abstract

Objective: To investigate the relationship between early T-lymphocyte levels after the first ¹³¹I therapy following total thyroidectomy and the efficacy of thyroid ablation at 6 months in patients with differentiated thyroid carcinoma(DTC). Methods: A total of 100 patients with DTC who underwent total thyroidectomy and ¹³¹I therapy in our hospital from May 2021 to May 2024 were selected as the research subjects. 24 weeks after ¹³¹I treatment, the patients were classified into satisfactory efficacy(ER), indeterminate efficacy(IDR), biochemical non-response(BIR), and structural non-response(SIR) groups based on the treatment outcome. ER and IDR were classified as the effective group, while BIR and SIR were classified as the ineffective group. Repeated measures ANOVA was used to compare the early T lymphocyte levels of the effective and ineffective groups after ¹³¹I treatment. Generalized linear mixed models(GLMMs) were used to analyze the relationship between T lymphocyte levels and the effect of thyroid ablation. Subgroup analysis was conducted to test the stability of the association between T lymphocyte levels and the efficacy of thyroid ablation. Restricted cubic spline was used to analyze the non-linear dose-response relationship between T lymphocyte subsets at 8 weeks after treatment and the efficacy of thyroid ablation. Receiver operating characteristic curve(ROC) analysis was used to evaluate the predictive efficacy of T lymphocyte levels for the thyroid ablation outcome at 6 months after total thyroidectomy. Results: (1)Compared with before treatment, the levels of CD3 ⁺, CD4 ⁺, and CD4 ⁺/CD8 ⁺ in both the effective and ineffective groups increased after treatment(P＜0.05), while the CD8 ⁺ level decreased(P＜0.05). Compared with the ineffective group, the levels of CD3 ⁺, CD4 ⁺, CD4 ⁺/CD8 ⁺, FT ₃, FT ₄, blood calcium, and iPTH in the effective group increased at different time points(P＜0.05), while the levels of CD8 ⁺ and TSH decreased(P＜0.05). (2)The results of GLMMs indicated that the level of T lymphocytes was associated with ineffective ablation after ¹³¹I treatment for half a year(P＜0.001). (3)Subgroup analysis showed that the correlation between the level of T lymphocytes and the efficacy of ablation was stable in the serum TSH subgroup, and there was no significant interaction between subgroups(P interaction＞0.05). (4)The analysis by restricted cubic splines showed that the level of T lymphocytes in patients 8 weeks after ¹³¹I treatment had a nonlinear dose-response relationship with the efficacy of ablation(P＜0.05), and the levels of ΔCD3 ⁺, ΔCD4 ⁺, and ΔCD4 ⁺/CD8 ⁺ were positively correlated with the efficacy of ablation, while the level of ΔCD8 ⁺ was negatively correlated with the efficacy of ablation. (5)ROC analysis showed that the AUCs of ΔCD3 ⁺, ΔCD4 ⁺, ΔCD8 ⁺, and ΔCD4 ⁺/CD8 ⁺ for predicting the efficacy of ablation at 8 weeks after treatment were 0.64(95%CI: 0.32~0.76), 0.77(95%CI: 0.46~0.84), 0.75(95%CI: 0.50~0.87), and 0.85(95%CI: 0.67~0.94), respectively, and the cut-off values were 58.56, 33.23, 29.74, and 1.16, respectively. Conclusion: Early changes in T-lymphocyte immune function after the first ¹³¹I treatment after total resection of differentiated thyroid cancer were significantly correlated with the efficacy of nail clearance after six months, in which the changes in CD4 ⁺/CD8 ⁺ ratio after 8 weeks of treatment were of high value in predicting the efficacy of nail clearance, and could be used as a potential immune monitoring index.

关键词

甲状腺癌 / 分化型 / ¹³¹I治疗 / T淋巴细胞 / 甲状腺清除

Key words

Thyroid cancer / differentiated type / ¹³¹I treatment / T lymphocytes / Thyroid ablation

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