分化型甲状腺癌远处转移发生放射性碘难治的危险因素及预测指标

单婵婵; 仲爱生; 蔡刚明; 张健

doi:10.3760/cma.j.cn321828-20240129-00043

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中华核医学与分子影像杂志

• 临床研究 •

ENGLISH ABSTRACT

分化型甲状腺癌远处转移发生放射性碘难治的危险因素及预测指标

作者及单位信息

出版日期： 2024 -12 -25 ·

DOI： 10.3760/cma.j.cn321828-20240129-00043

Risk factors and predictors of radioactive iodine refractory in differentiated thyroid cancer with distant metastasis

Authors Info & Affiliations

Shan Chanchan

Department of Oncology, JiangYuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China

Zhong Aisheng

Department of Oncology, JiangYuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China

Cai Gangming

Gene Laboratory, JiangYuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China

Zhang Jian

Department of Orthopedics, Central Hospital Affiliated to Jiangnan University, Wuxi 214001, China

Published： 2024 -12 -25 ·

DOI： 10.3760/cma.j.cn321828-20240129-00043

APP内阅读

摘要

目的探讨分化型甲状腺癌(DTC)远处转移发生放射性碘(RAI)难治(RAIR)的危险因素及预测指标。

方法回顾性分析2007年1月至2023年11月在江苏省原子医学研究所附属江原医院接受 ¹³¹I治疗的140例DTC远处转移患者[男51例、女89例，年龄51(14，82)岁]资料。根据 ¹³¹I治疗效果，分为RAIR组(84例)和RAI治疗有效(RAIE)组(56例)。采用两独立样本 t检验、Mann－Whitney U检验、 χ ²检验比较2组患者的一般临床资料、B－Raf原癌基因丝/苏氨酸蛋白激酶(BRAF) ^V600E和端粒酶反转录酶启动子(TERTp)突变，采用多因素logistic回归分析RAIR的影响因素。

结果RAIR组与RAIE组在年龄、年龄≥55岁、肿瘤最大径、RAI累积剂量、转移类型、术前甲状腺球蛋白(pre－Tg)差异均有统计学意义( χ ²值：7.78、9.03， t值：2.44～2.74， z＝－3.92，均 P<0.05)。RAIR组TERTp突变率为39.39%(26/66)，明显高于RAIE组(2.17%，1/46; χ ²＝20.97， P<0.001)；RAIR组和RAIE组BRAF ^V600E突变率为41.79%(28/67)和40.00%(20/50)，差异无统计学意义( χ ²＝0.04， P＝0.846)。Logistic回归分析示pre－Tg高水平和TERTp突变是RAIR发生的独立危险因素。

结论TERTp突变和pre－Tg高水平为RAIR发生的独立危险因素，二者可能成为具有潜力的预测RAIR的指标。

关键词：甲状腺肿瘤;肿瘤转移;放射疗法;碘放射性同位素;危险因素;预测

ABSTRACT

ObjectiveTo investigate the risk factors and prognostic indicators of radioactive iodide refractory (RAIR) in differentiated thyroid cancer (DTC) with distant metastasis (DM).

MethodsFrom January 2007 to November 2023, 140 DM-DTC patients who received ¹³¹I therapy in JiangYuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine were retrospectively conducted. According to the effect of ¹³¹I treatment, 84 cases in the RAIR group and 56 cases in the radioactive iodide efficient (RAIE) group were finally included. The general clinical data, B-Raf proto-oncogene, serine/threonine kinase (BRAF) ^V600E and telomerase reverse transcriptase promoter (TERTp) mutations were compared between the two groups by independent-sample t test, Mann-Whitney U test and χ ² test. Multiple logistic regression was used to analyze the influencing factors of RAIR.

ResultsThere were significant differences between the RAIR group and the RAIE group in age, age≥55 years, tumor maximum diameter, cumulative dose of radioactive iodide, type of metastasis and preoperative thyroglobulin (pre-Tg) ( χ ² values: 7.78 and 9.03, t values: 2.44-2.74, z=-3.92, all P<0.05). The TERTp mutation rate in RAIR group was 39.39%(26/66), which was significantly higher than that in RAIE group (2.17%(1/46); χ ²=20.97, P<0.001). The BRAF ^V600E mutation rate was 41.79%(28/67) in the RAIR group and 40.00%(20/50) in the RAIE group, with no significant difference ( χ ²=0.04, P=0.846). Logistic regression analysis found that high pre-Tg level and TERTp mutation were independent risk factors for RAIR occurrence.

ConclusionTERTp mutation and high pre-Tg level are independent risk factors for RAIR occurrence, and they may be potential indicators for predicting RAIR.

KEYWORDS： Thyroid neoplasms;Neoplasm metastasis;Radiotherapy;Iodine radioisotopes;Risk factors;Forecasting

Corresponding author: Zhang Jian, Email: mocdef.6ab21jzbxxjz

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引用本文

单婵婵,仲爱生,蔡刚明,等. 分化型甲状腺癌远处转移发生放射性碘难治的危险因素及预测指标[J]. 中华核医学与分子影像杂志,2024,44(12)：736-740.

DOI:10.3760/cma.j.cn321828-20240129-00043

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大约10%分化型甲状腺癌(differentiated thyroid cancer, DTC)患者具有高度侵袭性病程，其特征为广泛淋巴结转移和远处转移(distant metastases, DM) ^{[
1
]}。当发生DM时，最常见的转移部位是肺和骨，这些患者大多不能手术，并且由于缺乏碘摄取的能力，往往对放射性碘(radioactive iodide, RAI)治疗无反应，可能危及生命 ^{[
2
]}。因此，及早发现RAI难治(RAI refractory, RAIR)DTC有助于制定治疗方案，避免不必要的RAI治疗。

甲状腺球蛋白(thyroglobulin, Tg)是一种由甲状腺滤泡细胞分泌的糖蛋白，血清Tg有助于预测DTC术后复发 ^{[
3
]}。然而，术前Tg(preoperative Tg, pre－Tg)的诊断价值仍存在争议。B－Raf原癌基因丝/苏氨酸蛋白激酶(B－Raf proto－oncogene, serine/threonine kinase, BRAF) ^V600E和端粒酶反转录酶启动子(telomerase reverse transcriptase promoter, TERTp)突变已被证实与DM的甲状腺乳头状癌RAIR密切相关 ^{[
4
]}，但这些发现仍需要进一步研究证实和推广。本研究回顾性分析经 ¹³¹I治疗的DM－DTC患者，探讨其RAIR的相关危险因素，及早预测发生RAIR的可能性，辅助临床制定治疗方案。

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