Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer.

IF 7 2区医学 Q1 ONCOLOGY Chinese Journal of Cancer Research Pub Date : 2024-02-29 DOI:10.21147/j.issn.1000-9604.2024.01.03

Zhuanzhuan Mu, Xin Zhang, Dongquan Liang, Jugao Fang, Ge Chen, Wenting Guo, Di Sun, Yuqing Sun, Zhentian Kai, Lisha Huang, Jun Liang, Yansong Lin

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Abstract

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.

Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel (ThyroLead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification (MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.

Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIR-DTC. Genetic alterations were identified in 90% of all the patients, with BRAF (59.7% vs. 17.3%), TERT promoter (43.9% vs. 7.4%), and TP53 mutations (11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions (15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness (P<0.001), with an odds ratio (OR) of high to low MRS of 7.52 [95% confidence interval (95% CI), 3.96-14.28; P<0.001] and an OR of intermediate to low MRS of 3.20 (95% CI, 1.01-10.14; P=0.041).

Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

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利用远处转移性分化型甲状腺癌的分子改变对放射性碘难治性进行风险分层。

目的：放射性碘难治性分化型甲状腺癌（RAIR-DTC）患者往往被延误诊断，治疗方案有限。RAI 难治性与潜在遗传特征之间的相关性尚未得到广泛研究：方法：招募远处转移性 DTC 的成年患者，并分配他们接受定制的 26 个基因面板（ThyroLead）的新一代测序。患者被分为RAIR-DTC组和非RAIR组，以确定临床病理和分子特征的差异。根据发现的分子改变与 RAI 难治性之间的关联构建分子风险分层（MRS），并将结果分为高、中、低 MRS：结果：共纳入了 220 例远处转移患者，其中 63.2% 被确定为 RAIR-DTC。90%的患者都发现了基因改变，RAIR-DTC组的BRAF（59.7%对17.3%）、TERT启动子（43.9%对7.4%）和TP53突变（11.5%对3.7%）发生率高于非RAIR组，但RET融合（15.8%对39.5%）的发生率与非RAIR组相反。BRAF和TERT启动子是RAIR-DTC的独立预测因子，占RAIR-DTC患者的67.6%。MRS 与 RAI 难治性密切相关（PConclusions：分子改变与 RAI 难治性相关，BRAF 和 TERT 启动子突变是主要因素，其次是 TP53 和 DICER1 突变。MRS可作为一种有价值的工具，用于预测临床结果和指导精准治疗干预。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chinese Journal of Cancer Research 医学-肿瘤学

自引率

9.80%

发文量

1726

审稿时长

4.5 months

期刊介绍： Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013. CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.