临床研究
ENGLISH ABSTRACT
甲状腺乳头状癌患者首次 131I治疗前后外周血淋巴细胞亚群的差异分布对 131I疗效的预测价值
张君宇
樊迪
师志勇
罗天娥
武志芳
王红亮
陆克义
杨素云
吴力翔
胡婷婷
牟媛媛
李思进
刘海燕
作者及单位信息
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DOI: 10.3760/cma.j.cn321828-20240119-00026
Predictive value of the differential distribution of peripheral lymphocyte subsets before and after the first 131I treatment on therapeutic response in patients with papillary thyroid cancer
Zhang Junyu
Fan Di
Shi Zhiyong
Luo Tiane
Wu Zhifang
Wang Hongliang
Lu Keyi
Yang Suyun
Wu Lixiang
Hu Tingting
Mou Yuanyuan
Li Sijin
Liu Haiyan
Authors Info & Affiliations
Zhang Junyu
Department of Nuclear Medicine, First Hospital of Shanxi Medical University; Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Taiyuan 030001, China
Fan Di
Department of Nuclear Medicine, First Hospital of Shanxi Medical University; Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Taiyuan 030001, China
Shi Zhiyong
Department of Nuclear Medicine, First Hospital of Shanxi Medical University; Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Taiyuan 030001, China
Luo Tiane
Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan 030001, China
Wu Zhifang
Department of Nuclear Medicine, First Hospital of Shanxi Medical University; Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Taiyuan 030001, China
Wang Hongliang
Department of Nuclear Medicine, First Hospital of Shanxi Medical University; Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Taiyuan 030001, China
Lu Keyi
Department of Nuclear Medicine, First Hospital of Shanxi Medical University; Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Taiyuan 030001, China
Yang Suyun
Department of Nuclear Medicine, First Hospital of Shanxi Medical University; Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Taiyuan 030001, China
Wu Lixiang
Department of Nuclear Medicine, First Hospital of Shanxi Medical University; Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Taiyuan 030001, China
Hu Tingting
Department of Nuclear Medicine, First Hospital of Shanxi Medical University; Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Taiyuan 030001, China
Mou Yuanyuan
Department of Nuclear Medicine, First Hospital of Shanxi Medical University; Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Taiyuan 030001, China
Li Sijin
Department of Nuclear Medicine, First Hospital of Shanxi Medical University; Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Taiyuan 030001, China
Liu Haiyan
Department of Nuclear Medicine, First Hospital of Shanxi Medical University; Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Taiyuan 030001, China
·
DOI: 10.3760/cma.j.cn321828-20240119-00026
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摘要

目的探讨首次 131I治疗前后外周血淋巴细胞亚群的差异分布对甲状腺乳头状癌(PTC)患者 131I治疗效果反应的预测价值。

方法回顾性研究2021年1月至2021年8月间山西医科大学第一医院的46例甲状腺全切术后接受 131I治疗的PTC患者(男16例、女30例,年龄20~77岁),患者于 131I治疗前1~2 d和 131I治疗后30 d检测外周血淋巴细胞亚群[T、B、CD4 T、CD8 T、自然杀伤(NK)、辅助性T(Th)1、Th2、Th17和调节性T(Treg)淋巴细胞]的绝对计数。依据血清学和影像学证据,将 131I治疗后6~12个月的治疗反应分为疗效满意(ER)和疗效不满意(NER),分析2组间 131I治疗前刺激性甲状腺球蛋白(psTg)、临床基线特征差异(两独立样本 t检验、配对 t检验、Mann-Whitney U检验)和 131I治疗前后淋巴细胞亚群对治疗反应的预测价值[logistic回归分析、ROC曲线和决策曲线分析(DCA)]。

结果在ER组(33例)和NER组(13例)内,与 131I治疗前相比, 131I治疗后30 d大部分淋巴细胞亚群有不同程度降低:ER组T、B、CD4 T和Th1淋巴细胞,NER组T、B、CD4 T、Th1、Th2、Th17和Treg淋巴细胞( t值:2.41~9.57,均 P<0.05)。 131I治疗前NER组psTg水平、Th2、Th17和Treg淋巴细胞数量高于ER组( t值:-3.32~-2.48, U=29.00,均 P<0.05), 131I治疗后NER组大部分淋巴细胞亚群(T、B、CD4 T、CD8 T、Th1和Treg淋巴细胞)高于ER组但差异均无统计学意义( t值:-1.12~-0.06,均 P>0.05)。 131I治疗前的Th2淋巴细胞[比值比( OR)=25.00,95% CI:1.36~459.10, P=0.030]是NER的危险因素。ROC曲线分析示,psTg、Th2淋巴细胞预测治疗反应的AUC分别为0.932、0.790,拟合psTg+Th2淋巴细胞亚群的AUC为0.958。DCA示阈值概率为10%~60%时,psTg、Th2淋巴细胞和拟合psTg+Th2淋巴细胞亚群的曲线均高于极端曲线,提示效果较好。

结论PTC患者 131I治疗后30 d,大部分淋巴细胞亚群呈现不同程度降低,且NER组降低更明显;Th2淋巴细胞可能是 131I治疗反应不佳的危险因素,对 131I治疗的疗效反应具有一定预测价值。

甲状腺肿瘤;放射疗法;碘放射性同位素;淋巴细胞亚群;治疗结果;预测
ABSTRACT

ObjectiveTo investigate the predictive value of differential distribution of peripheral lymphocyte subsets before and after the first 131I treatment on the therapeutic response to 131I treatment in patients with papillary thyroid cancer (PTC).

MethodsA retrospective study was conducted on 46 PTC patients (16 males, 30 females, age 20-77 years) who underwent total thyroidectomy and received 131I treatment between January 2021 and August 2021 in First Hospital of Shanxi Medical University. Peripheral blood lymphocyte subsets (T, B, CD4 + T, CD8 + T, natural killer (NK), helper T (Th)1, Th2, Th17, and regulatory T (Treg) cells) were measured 1-2 d before and 30 d after 131I treatment. Based on serological and imaging evidence, therapeutic response at 6-12 months post- 131I therapy was categorized as either excellent response (ER) or non-excellent response (NER). Differences of preablative stimulated thyroglobulin (psTg) and clinical baseline characteristics between two groups were assessed by using independent-sample t test, paired t test, or Mann-Whitney U test. Predictive value of lymphocyte subsets before and after 131I treatment for therapeutic response was assessed through logistic regression analysis, ROC curve analysis, and decision curve analysis (DCA).

ResultsIn ER group ( n=33) and NER group ( n=13), most lymphocyte subsets showed different degrees of reduction 30 d after 131I treatment compared to before 131I treatment, such as T, B, CD4 + T and Th1 cells in ER group, as well as T, B, CD4 + T, Th1, Th2, Th17, and Treg cells in NER group ( t values: 2.41-9.57, all P<0.05). Before 131I treatment, NER group had significantly higher levels of psTg, Th2, Th17, and Treg cells compared to the ER group ( t values: from -3.32 to -2.48, U=29.00, all P<0.05). After 131I treatment, most of lymphocyte subsets in NER group (T, B, CD4 + T, CD8 + T, Th1 and Treg cells) showed higher trend than those in ER group but without statistical significances ( t values: from -1.12 to -0.06, all P>0.05). Th2 cells before 131I treatment (odds ratio ( OR)=25.00, 95% CI: 1.36-459.10, P=0.030) was identified as a risk factor for NER. ROC curve analysis indicated that AUCs of psTg and Th2 cells for predicting therapeutic response were 0.932 and 0.790, respectively, which was 0.958 for the combined psTg and Th2 cells. DCA showed that within the threshold probability range of 10%-60%, the curves for psTg, Th2 cells, and the combined psTg and Th2 cells were all higher than the extreme curve, suggesting good effect.

ConclusionsMost lymphocyte subsets decrease to varying degrees, and NER group shows a significant decrease 30 d after 131I treatment. Th2 cells may be a risk factor for poor response to 131I treatment, providing a certain value in predicting the therapeutic response to 131I treatment.

Thyroid neoplasms;Radiotherapy;Iodine radioisotopes;Lymphocyte subsets;Treatment outcome;Forecasting
Liu Haiyan, Email: mocdef.6ab213021-nayiahuil
引用本文

张君宇,樊迪,师志勇,等. 甲状腺乳头状癌患者首次 131I治疗前后外周血淋巴细胞亚群的差异分布对 131I疗效的预测价值 [J]. 中华核医学与分子影像杂志,2024,44(12):730-735.

DOI:10.3760/cma.j.cn321828-20240119-00026

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甲状腺癌的发病率呈逐年上升趋势 [ 1 ]。甲状腺乳头状癌(papillary thyroid cancer, PTC)是最常见的病理类型,占80%~90% [ 2 ]。PTC患者的生存率较高,但仍有15%~30%的患者经历复发,5%~10%的患者发生远处转移 [ 3 ]。免疫系统在PTC的发生和发展中起着关键作用 [ 4 ]。淋巴细胞的浸润与甲状腺肿瘤体积、分期和侵袭性等特征有关,影响PTC患者预后 [ 5 ]
甲状腺全切术后 131I治疗有利于清除术后残留的甲状腺组织、局部癌灶、潜在的或远处的病灶、对PTC患者进行血清甲状腺球蛋白(thyroglobulin, Tg)监测和疾病分层 [ 6 ]。关于 131I治疗前后外周血淋巴细胞各亚群计数的变化及其与治疗效果的关系,鲜有研究报道。本研究旨在描述不同治疗效果的PTC患者接受 131I治疗前后淋巴细胞亚群[T、B、CD4 T、CD8 T、自然杀伤(natural killer, NK)、辅助性T(helper T, Th)1、Th2、Th17和调节性T(regulatory T, Treg)淋巴细胞]的差异分布,并探讨淋巴细胞亚群对 131I治疗效果的预测价值。
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备注信息
A
刘海燕,Email: mocdef.6ab213021-nayiahuil
B

张君宇:研究设计、论文撰写;樊迪、罗天娥:数据分析;师志勇、胡婷婷、牟媛媛:研究实施、数据整理;武志芳、王红亮、陆克义、杨素云、吴力翔:论文修改;李思进、刘海燕:研究指导、论文审阅、经费支持

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所有作者声明无利益冲突
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国家自然科学基金 (82372009)
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