Abstract：
OBJECTIVE: Radioiodine (RAI) therapy remains the gold-standard approach for distant metastatic differentiated thyroid cancer (TC). The main objective of our work was to identify the clinical and molecular markers that may help to predict RAI avidity and RAI therapy response of metastatic lesions in a cohort of papillary thyroid cancer (PTC) patients.
METHODS: We performed a retrospective analysis of 122 PTC patients submitted to RAI therapy due to distant metastatic disease. We also analysed, through next-generation sequencing, a custom panel of 78 genes and rearrangements, in a smaller cohort of 31 metastatic PTC, with complete follow-up, available RAI therapy data, and existing tumour sample at our centre.
RESULTS: The most frequent outcome after RAI therapy was progression of disease in 59.0% of cases (n = 71), with median estimate progression-free survival of 30 months. RAI avidity was associated with PTC subtype, age and stimulated thyroglobulin at first RAI therapy for metastatic disease. The most frequently altered genes in the cohort of 31 PTC patients\' primary tumours were RAS isoforms (54.8%) and TERT promoter (TERTp) (51.6%). The presence of BRAF p.V600E or RET/PTC alterations was associated with lower avidity (p = 0.012). TERTp mutations were not associated with avidity (p = 1.000) but portended a tendency for a higher rate of progression (p = 0.063); similar results were obtained when RAS and TERTp mutations coexisted (p = 1.000 and p = 0.073, respectively).
CONCLUSIONS: Early identification of molecular markers in primary tumours may help to predict RAI therapy avidity, the response of metastatic lesions and to select the patients that may benefit the most from other systemic therapies.
METHODS: We performed a retrospective analysis of 122 PTC patients submitted to RAI therapy due to distant metastatic disease. We also analysed, through next-generation sequencing, a custom panel of 78 genes and rearrangements, in a smaller cohort of 31 metastatic PTC, with complete follow-up, available RAI therapy data, and existing tumour sample at our centre.
RESULTS: The most frequent outcome after RAI therapy was progression of disease in 59.0% of cases (n = 71), with median estimate progression-free survival of 30 months. RAI avidity was associated with PTC subtype, age and stimulated thyroglobulin at first RAI therapy for metastatic disease. The most frequently altered genes in the cohort of 31 PTC patients\' primary tumours were RAS isoforms (54.8%) and TERT promoter (TERTp) (51.6%). The presence of BRAF p.V600E or RET/PTC alterations was associated with lower avidity (p = 0.012). TERTp mutations were not associated with avidity (p = 1.000) but portended a tendency for a higher rate of progression (p = 0.063); similar results were obtained when RAS and TERTp mutations coexisted (p = 1.000 and p = 0.073, respectively).
CONCLUSIONS: Early identification of molecular markers in primary tumours may help to predict RAI therapy avidity, the response of metastatic lesions and to select the patients that may benefit the most from other systemic therapies.
摘要：
目的：放射性碘（RAI）治疗仍然是远处转移性分化型甲状腺癌（TC）的金标准方法。我们工作的主要目的是确定临床和分子标志物，这些标志物可能有助于预测甲状腺乳头状癌（PTC）患者队列中转移性病变的RAI亲和力和RAI治疗反应。
方法：我们对122例因远处转移性疾病而接受RAI治疗的PTC患者进行了回顾性分析。我们还分析了,通过下一代测序，一个由78个基因和重排组成的定制小组，在一个由31个转移性PTC组成的较小队列中，有了完整的后续行动，可用的RAI治疗数据，和我们中心现有的肿瘤样本。
结果：RAI治疗后最常见的结果是59.0％的病例（n=71）的疾病进展，中位无进展生存期为30个月。RAI亲和力与PTC亚型有关,转移性疾病首次RAI治疗时的年龄和刺激的甲状腺球蛋白。31例PTC原发肿瘤患者队列中最常见的基因是RAS亚型(54.8%)和TERT启动子(TERTp)(51.6%)。BRAFp.V600E或RET/PTC改变的存在与较低的亲和力相关(p=0.012)。TERTp突变与亲合力无关（p=1.000），但预示着进展速率较高的趋势（p=0.063）；当RAS和TERTp突变共存时获得了类似的结果（分别为p=1.000和p=0.073）。
结论：早期识别原发性肿瘤中的分子标志物可能有助于预测RAI治疗的亲和力，转移性病变的反应，并选择可能从其他全身治疗中受益最大的患者。
方法：我们对122例因远处转移性疾病而接受RAI治疗的PTC患者进行了回顾性分析。我们还分析了,通过下一代测序，一个由78个基因和重排组成的定制小组，在一个由31个转移性PTC组成的较小队列中，有了完整的后续行动，可用的RAI治疗数据，和我们中心现有的肿瘤样本。
结果：RAI治疗后最常见的结果是59.0％的病例（n=71）的疾病进展，中位无进展生存期为30个月。RAI亲和力与PTC亚型有关,转移性疾病首次RAI治疗时的年龄和刺激的甲状腺球蛋白。31例PTC原发肿瘤患者队列中最常见的基因是RAS亚型(54.8%)和TERT启动子(TERTp)(51.6%)。BRAFp.V600E或RET/PTC改变的存在与较低的亲和力相关(p=0.012)。TERTp突变与亲合力无关（p=1.000），但预示着进展速率较高的趋势（p=0.063）；当RAS和TERTp突变共存时获得了类似的结果（分别为p=1.000和p=0.073）。
结论：早期识别原发性肿瘤中的分子标志物可能有助于预测RAI治疗的亲和力，转移性病变的反应，并选择可能从其他全身治疗中受益最大的患者。
