OBJECTIVE: To evaluate the treatment period and overall survival time for each genetic alteration in advanced thyroid carcinoma that requires drug therapy.
METHODS: We conducted a retrospective observational study using a national database in Japan, which included 552 cases of thyroid carcinoma out of 53,543 patients in the database.
RESULTS: The database included anaplastic thyroid carcinoma (23.6%), poorly differentiated thyroid carcinoma (10.0%), and differentiated thyroid carcinoma (66.4%). The most common genetic abnormalities were TERT promoter (66.3%), BRAF (56.7%), and TP53 (32.2%). The typical driver genes were BRAF V600E (55.0%), RAS (18.5%), RET fusion (4.7%), NTRK fusion (1.6%), and ALK fusion (0.4%). The most common regimen was lenvatinib, and the time to treatment failure was not different despite the presence of BRAF or RAS mutations. In differentiated thyroid carcinoma and poorly differentiated thyroid carcinoma, TP53 alterations independently predicted worse overall survival (hazard ratio = 2.205, 95% confidence interval: 1.135-4.283). In anaplastic thyroid carcinoma, no genetic alterations were associated with overall survival.
CONCLUSIONS: Genetic abnormalities with treatment options were found in 62.7% of advanced thyroid carcinomas. TP53 abnormality was an independent poor prognostic factor for overall survival in differentiated thyroid carcinoma. The time to treatment failure for lenvatinib was not different based on genetic profile.
目的:评估需要药物治疗的晚期甲状腺癌每个基因改变的治疗周期和总生存期。
方法:我们使用日本的国家数据库进行了一项回顾性观察研究,其中包括数据库中53,543例患者中的552例甲状腺癌。
结果:数据库包括甲状腺未分化癌(23.6%),低分化甲状腺癌(10.0%),分化型甲状腺癌(66.4%)。最常见的遗传异常是TERT启动子(66.3%),BRAF(56.7%),TP53(32.2%)。典型的驱动基因为BRAFV600E(55.0%),RAS(18.5%),RET融合(4.7%),NTRK融合(1.6%),和ALK融合(0.4%)。最常见的方案是lenvatinib,尽管存在BRAF或RAS突变,但治疗失败的时间没有差异.在分化型甲状腺癌和低分化型甲状腺癌中,TP53改变独立预测较差的总生存期(风险比=2.205,95%置信区间:1.135-4.283)。在间变性甲状腺癌中,没有遗传改变与总生存期相关.
结论:在62.7%的晚期甲状腺癌中发现了治疗方案的遗传异常。TP53异常是分化型甲状腺癌总生存期的独立不良预后因素。lenvatinib治疗失败的时间根据遗传特征没有差异。