具有放射性碘摄取远处转移的分化型甲状腺癌的临床结局和分子特征。
Clinical outcomes and molecular profile of differentiated thyroid cancers with radioiodine-avid distant metastases.
机构信息
Endocrinology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill-Cornell College of Medicine, New York, New York 10065, USA.
出版信息
J Clin Endocrinol Metab. 2013 May;98(5):E829-36. doi: 10.1210/jc.2012-3933. Epub 2013 Mar 26.
BACKGROUND
Radioiodine (RAI) remains the mainstay of therapy for RAI-avid (RAIA) distant metastatic thyroid carcinoma. We previously demonstrated that RAI-refractory distant metastatic thyroid cancers commonly harbor BRAF mutations. However, the molecular profile of RAIA metastatic thyroid cancer is unknown. Here we describe the mutational profile of thyroid tumors from follicular cell-derived cancer (FCDTC) patients presenting with RAIA distant metastases. In addition, we aimed to correlate clinical outcomes of RAI therapy with clinicopathological factors and tumor mutational status.
METHODS
We retrospectively identified 43 patients with FCDTC who had RAI uptake in the lungs and/or bones on their initial ¹³¹I postablation scan. Primary tumors were genotyped for known mutations in thyroid cancer genes. Structural response to RAI was assessed 6-18 months after each administered RAI activity and at the end of follow-up.
RESULTS
RAS, BRAF, RET/PTC, and PIK3CA mutations were found in 42, 23, 10, and 2% of tumors, respectively, and the remaining 23% were wild type. None of these patients achieved cure after repeat RAI therapies, and most patients (54%) experienced disease progression despite repeated RAI administration. There was an increased prevalence of RAS mutations in these RAIA tumors. RAS-mutant cancers were more likely to concentrate iodine on diagnostic whole body scans. Despite this, structural response to RAI was not influenced by tumor genotype.
CONCLUSIONS
RAIA metastatic FCDTC are overrepresented with RAS mutations, whereas RAI refractory metastatic thyroid cancers are enriched with BRAF mutations. Despite a seemingly preserved ability to concentrate iodine, RAI therapy is ineffective in achieving cure in most patients with RAIA metastatic FCDTC, even in RAS-mutant disease. These poor outcomes may be improved based on recent evidence that pretreatment with MAPK kinase 1/2 inhibitors enhances responses to RAI, particularly in patients with RAS-mutant tumors.
背景
放射性碘（RAI）仍然是治疗 RAI 亲和性（RAIA）远处转移性甲状腺癌的主要方法。我们之前证明，RAI 难治性远处转移性甲状腺癌通常存在 BRAF 突变。然而，RAIA 转移性甲状腺癌的分子特征尚不清楚。在这里，我们描述了来自滤泡细胞来源的癌症（FCDTC）患者的甲状腺肿瘤的突变谱，这些患者表现出 RAIA 远处转移。此外，我们旨在将 RAI 治疗的临床结果与临床病理因素和肿瘤突变状态相关联。
方法
我们回顾性地确定了 43 名 FCDTC 患者，他们在初始¹³¹I 后吸收扫描中在肺部和/或骨骼中显示出 RAI 摄取。对原发性肿瘤进行甲状腺癌基因中已知突变的基因分型。在每次给予的 RAI 活性后 6-18 个月以及随访结束时评估对 RAI 的结构反应。
结果
在肿瘤中分别发现 RAS、BRAF、RET/PTC 和 PIK3CA 突变分别为 42%、23%、10%和 2%，其余 23%为野生型。这些患者在重复 RAI 治疗后均未治愈，大多数患者（54%）尽管重复给予 RAI，但仍出现疾病进展。这些 RAIA 肿瘤中 RAS 突变的发生率增加。RAS 突变型癌症更有可能在诊断性全身扫描中集中碘。尽管如此，RAI 治疗的结构反应不受肿瘤基因型的影响。
结论
RAIA 转移性 FCDTC 中 RAS 突变过度表达，而 RAI 难治性转移性甲状腺癌则富含 BRAF 突变。尽管似乎保留了浓缩碘的能力，但 RAI 治疗在大多数 RAIA 转移性 FCDTC 患者中无法治愈，即使在 RAS 突变疾病中也是如此。根据最近的证据，基于 MAPK 激酶 1/2 抑制剂的预处理可增强对 RAI 的反应，特别是在 RAS 突变型肿瘤患者中，这些不良结果可能会得到改善。
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