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

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

机构地区：[1]Department of Nuclear Medicine,State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College(PUMC)Hospital,Chinese Academy of Medical Sciences&PUMC,Beijing 100730,China [2]Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine,Beijing 100730,China [3]Pepperdine University Graduate School of Education and Psychology,Los Angeles 90045,USA [4]Department of Head and Neck Surgery,Affiliated Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China [5]Department of General Surgery,State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College(PUMC)Hospital,Chinese Academy of Medical Sciences&PUMC,Beijing 100730,China [6]Central Laboratory,State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College(PUMC)Hospital,Chinese Academy of Medical Sciences&PUMC,Beijing 100730,China [7]Department of Bioinformatics,Zhejiang Shaoxing Topgen Biomedical Technology Co.,Ltd,Shanghai 201321,China [8]Department of Medicine,Zhejiang Shaoxing Topgen Biomedical Technology Co.,Ltd,Shanghai 201321,China [9]Department of Oncology,Peking University International Hospital,Beijing 102206,China

出　　处：《Chinese Journal of Cancer Research》2024年第1期25-35,共11页中国癌症研究（英文版）

基　　金：supported by the Project on InterGovernmental International Scientific and Technological Innovation Cooperation in National Key Projects of Research and Development Plan (No. 2019YFE0106400);the National Natural Science Foundation of China (No. 81771875)。

摘　　要：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(Thyro Lead). 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 RAIRDTC. 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.

关 键 词：Differentiated thyroid cancer distant metastases genetic alterations RAI refractoriness molecular risk stratification 

分 类 号：R736.1[医药卫生—肿瘤]