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BRAF V600E 与 TERT 启动子突变的遗传二重奏预测甲状腺乳头状癌放射性碘治疗的疗效不佳。

The genetic duet of BRAF V600E and TERT promoter mutations predicts the poor curative effect of radioiodine therapy in papillary thyroid cancer.

机构信息

Department of Nuclear Medicine, the Second Hospital, Cheeloo College of Medicine, Shandong University, No. 247 Road, Tianqiao District, Jinan, 250033, China.

出版信息

Eur J Nucl Med Mol Imaging. 2022 Aug;49(10):3470-3481. doi: 10.1007/s00259-022-05820-x. Epub 2022 May 2.

Abstract

OBJECTIVE

The BRAF V600E and TERT promoter mutations are well known to be associated with poor clinical outcomes of papillary thyroid cancer (PTC). Radioactive iodide (RAI)-refractory can be evaluated in advance of treatment, for which predictive biomarkers may be helpful. The present study is to analyze the correlation of both mutations with the curative effect of radioiodine therapy.

METHODS

A total of 126 patients who underwent RAI therapy from October 2016 to August 2019 were recruited. Treatment and follow-up were defined according to criteria used in the 2015 ATA guidelines. The RAI response of patients was assessed as excellent response (ER) and RAI-refractory at the end of follow-up.

RESULTS

When dividing the 126 patients into 4 groups, the no mutation, only BRAF V600E mutation, only TERT promoter mutation, and coexistence of two mutation groups were found in 15.8%, 68.3%, 2.4%, and 13.5% patients. RAI-refractory was found in 52.9% (9/17) patients with the coexisting BRAF and TERT mutations. In logistic regression analysis, M1, BRAF, and TERT mutation were confirmed to be independent factors predicting the RAI-refractory. Moreover, 35.3%, 41.2%, and 23.5% of patients in the BRAF and TERT mutation group were assessed as ER, SIR, and BIR respectively. Kaplan-Meier analyses revealed that the genetic duet of BRAF V600E and TERT promoter mutations was associated with a lower ER reached time.

CONCLUSIONS

We found that BRAF V600E and TERT promoter mutation is significantly correlated with the poor curative effect of RAI therapy in PTC.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: ChiCTR1800018760.

摘要

目的

BRAF V600E 和 TERT 启动子突变与甲状腺乳头状癌(PTC)的不良临床结局密切相关。放射性碘(RAI)难治性可在治疗前进行评估,此时预测生物标志物可能会有所帮助。本研究旨在分析这两种突变与放射性碘治疗疗效的相关性。

方法

共纳入 2016 年 10 月至 2019 年 8 月期间接受 RAI 治疗的 126 例患者。根据 2015 年 ATA 指南中的标准定义治疗和随访。在随访结束时评估患者的 RAI 反应为完全缓解(ER)和 RAI 难治性。

结果

当将 126 例患者分为 4 组时,无突变组、仅 BRAF V600E 突变组、仅 TERT 启动子突变组和两种突变共存组分别占 15.8%、68.3%、2.4%和 13.5%。BRAF 和 TERT 突变共存组的 17 例患者中,有 52.9%(9/17)发生 RAI 难治性。在逻辑回归分析中,M1、BRAF 和 TERT 突变被证实是预测 RAI 难治性的独立因素。此外,BRAF 和 TERT 突变组中分别有 35.3%、41.2%和 23.5%的患者被评估为 ER、SIR 和 BIR。Kaplan-Meier 分析显示,BRAF V600E 和 TERT 启动子突变的遗传偶联与较低的 ER 达到时间相关。

结论

我们发现 BRAF V600E 和 TERT 启动子突变与 PTC 的 RAI 治疗疗效不佳显著相关。

试验注册

ClinicalTrials.gov 标识符:ChiCTR1800018760。

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