局部晚期或转移性儿童及青少年分化型甲状腺癌的基因特征与临床特征及<sup>131</sup>I疗效的关系

孙迪; 孙郁青; 张鑫; 黄丽莎; 林岩松

doi:10.19401/j.cnki.1007-3639.2022.05.002

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局部晚期或转移性儿童及青少年分化型甲状腺癌的基因特征与临床特征及¹³¹I疗效的关系

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- 局部晚期或转移性儿童及青少年分化型甲状腺癌的基因特征与临床特征及¹³¹I疗效的关系
- The relationship between genetic characteristics and clinical characteristics and the efficacy of ¹³¹I therapy in children and adolescents with locally advanced or metastatic differentiated thyroid cancer
- 中国癌症杂志 2022年32卷第5期页码：380-387
- 作者机构：
  
  1. 中国医学科学院北京协和医学院北京协和医院核医学科,疑难重症及罕见病国家重点实验室,北京 100730
  2. 核医学分子靶向诊疗北京市重点实验室,北京 100730
  3. 浙江绍兴鼎晶生物医药科技股份有限公司,上海 201318
- 作者简介：
  
  [ "孙迪（ORCID: 0000-0002-5558-0829）,硕士在读 E-mail: mercurysd@163.com" ]
  [ "林岩松,主任医师,教授,博士研究生导师。现任中国医学科学院北京协和医学院北京协和医院核医学科副主任,兼任国家卫生健康委员会专业技术职称考试专家委员会专家,国际原子能机构RAS6074、RAS6083项目中国区协调员,中国临床肿瘤学会核医学专家委员会主任委员,中国医师学会科普分会甲状腺科普专家委员会主任委员,中国医疗保健国际交流促进会甲状腺疾病专业委员会副主任委员,中国研究型医院学会分子诊断专业委员会副主任委员,中国抗癌协会甲状腺癌专业委员会常委,北京医学会核医学分会常委、治疗学组组长等。从事治疗核医学工作,并致力于分化型甲状腺癌的术后评估、治疗决策、全程管理及碘难治性分化型甲状腺癌的诊断与后续治疗探索。多次获得国家自然科学基金及科技部国际合作项目等基金资助。三度荣获中华医学科技奖,两度荣获华夏医学科技奖。作为主编及主要执笔人完成多部国内甲状腺领域专家共识及指南。以第一作者及通信作者发表甲状腺领域相关文章120余篇,其中在SCI收录期刊上发表30余篇。" ]
- 基金信息：
  
  中国医学科学院中央级公益性科研院所基本科研业务费专项资金(2019XK320009);国家重点研发计划“政府间国际科技创新合作/港澳台科技创新合作”重点专项(2019YFE0106400)
- DOI：10.19401/j.cnki.1007-3639.2022.05.002
  中图分类号： R736.1
- 收稿：2022-04-15，
  
  修回：2022-05-04，
  
  纸质出版：2022-05-30
- 稿件说明：
移动端阅览
孙迪, 孙郁青, 张鑫, 等. 局部晚期或转移性儿童及青少年分化型甲状腺癌的基因特征与临床特征及¹³¹I疗效的关系[J]. 中国癌症杂志, 2022,32(5):380-387.

Di SUN, Yuqing SUN, Xin ZHANG, et al. The relationship between genetic characteristics and clinical characteristics and the efficacy of ¹³¹I therapy in children and adolescents with locally advanced or metastatic differentiated thyroid cancer[J]. China Oncology, 2022, 32(5): 380-387.
孙迪, 孙郁青, 张鑫, 等. 局部晚期或转移性儿童及青少年分化型甲状腺癌的基因特征与临床特征及¹³¹I疗效的关系[J]. 中国癌症杂志, 2022,32(5):380-387. DOI： 10.19401/j.cnki.1007-3639.2022.05.002.

Di SUN, Yuqing SUN, Xin ZHANG, et al. The relationship between genetic characteristics and clinical characteristics and the efficacy of ¹³¹I therapy in children and adolescents with locally advanced or metastatic differentiated thyroid cancer[J]. China Oncology, 2022, 32(5): 380-387. DOI： 10.19401/j.cnki.1007-3639.2022.05.002.

摘要

背景与目的：

儿童及青少年分化型甲状腺癌（differentiated thyroid cancer

DTC）的分子生物学特征及其临床指导意义尚不明确。本研究拟初步探讨局部晚期或转移性DTC患儿的基因特征分布及其与临床特征及

131

I疗效的关系。

方法：

采用甲状腺癌相关基因panel（ThyroLead

）对2020年12月

#x02014;2021年7月就诊于中国医学科学院北京协和医学院北京协和医院的儿童及青少年侵袭性DTC的原发灶进行测序

并回顾性收集患儿的临床病理学特征及

131

I治疗相关资料

分析其基因特征与其临床病理学特征及

131

I疗效的关系。

结果：

本队列纳入39例局部晚期或转移性患儿

可及数据中所有患儿均存在淋巴结转移

侧方区受累率达91.4%（32/35）

远处转移率达61.5%（24/39）。61.5%（24/39）的患儿检出甲状腺癌相关基因变异

其中以

RET

融合（38.5%

15/39）和

BRAF

V600E点突变（12.8%

5/39）最为常见。突变组与非突变组的临床特征差异无统计学意义（

0.05）。远处转移中

91.7%（22/24）的患儿在

131

I治疗后仍呈结构性疗效不佳（structural incomplete response

SIR）状态

其中9例患儿呈放射性碘难治（radioactive iodine-refractory

RAIR）状态。RAIR状态患儿中88.9%（8/9）检出相关基因变异

其中

NCOA

RET

融合占62.5%（5/8）。进一步将

RET

变异组患儿细化分组显示

与其他形式的

RET

融合相比

NCOA

RET

融合阳性者远处转移率更高（33.3%

88.9%

=0.089）

提示其具有更高的远处侵犯倾向。

结论：

局部晚期或转移性DTC患儿的基因突变以融合突变尤其是

RET

融合为主

其中

NCOA

RET

融合阳性者似乎显示出更强的侵袭性

更易呈RAIR状态。

Abstract

Background and purpose:

The molecular characteristics of differentiated thyroid cancer (DTC) in children and adolescents and its role in clinical practice remain unclear. This study intended to explore the genetic characteristics and its relationship with clinical characteristics and efficacy of

131

I therapy in locally advanced or metastatic pediatric and adolescent DTC patients.

Methods:

A thyroid cancer-related gene panel (ThyroLead

#x000ae;) was used to test the primary tumors from children and adolescents with DTC treated in Peking Union Medical College Hospital

Chinese Academy of Medical Sciences and Peking Union Medical College from December 2020 to July 2021. The samples were sequenced

the clinicopathologic

al characteristics and

131

I treatment history were retrospectively collected

and the relationship between their genetic characteristics and clinicopathological characteristics and the efficacy of

131

I therapy was analyzed.

Results:

All the 39 children present locally advanced or metastatic disease. All the children with accessible data had lymph node metastasis

91.4% (32/35) of whom had lateral lymph node metastasis

and 61.5% (24/39) patients had distant metastasis. Thyroid cancer-related gene variants were detected in 61.5% (24/39) of the patients

among which RET fusion (38.5%

15/39) and

BRAF

V600E point mutation (12.8%

5/39) were the most common. No statistically significant differences were found in clinical characteristics between the mutation group and the non-mutation group (

0.05). Most of the children (91.7%

22/24) with distant metastases remained structural incomplete response (SIR) status after

131

I treatment. Nine patients were considered radioactive iodine-refractory (RAIR) status

and 8 of them had thyroid cancer driver mutations

among which

NCOA

RET

accounted for 62.5% (5/8). Among cases with RET genetic variations

NCOA

RET

fusion-positive patients tended to present more distant metastasis than those with other forms of

RET

fusion (33.3%

88.9%

=0.089).

Conclusion:

Compared with point mutations

fusion gene mutations

especially

RET

fusions

are more common in locally advanced or metastatic pediatric and adolescent DTC patients.

NCOA

RET

fusion-positive tumor has more aggressive behaviors and are more likely to become RAIR.

关键词

Keywords

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DOI：10.19401/j.cnki.1007-3639.2022.05.002

摘要

Abstract

关键词

Keywords

references

局部晚期或转移性儿童及青少年分化型甲状腺癌的基因特征与临床特征及¹³¹I疗效的关系

The relationship between genetic characteristics and clinical characteristics and the efficacy of ¹³¹I therapy in children and adolescents with locally advanced or metastatic differentiated thyroid cancer