Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts.
Department of Otolaryngology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
Thyroid. 2019 Nov;29(11):1704-1707. doi: 10.1089/thy.2019.0041.
Medullary thyroid carcinoma (MTC) is most commonly associated with gene mutations. fusions have rarely been described, although not previously in pediatrics and not previously partnered with in MTC or any other cancer. A 10-year-old boy with progressive stridor was found to have metastatic MTC, including lung, lymph node, and adrenal metastases. Baseline calcitonin was 6703 pg/mL. While molecular testing was pending, he was treated empirically with the investigational selective RET inhibitor, LOXO-292, without improvement. Molecular testing revealed a novel - fusion. His therapy was changed to crizotinib and then to alectinib for improved tolerability. Calcitonin decreased to 663 pg/mL after 6 days of ALK inhibition. He remains on alectinib with ongoing response. A novel - fusion has now been implicated in a pediatric case of metastatic MTC. This fusion has profound clinical sensitivity to ALK inhibitors. This report expands the spectrum of fusions seen in MTC, including the first pediatric case of translocated MTC. This novel fusion with has not previously been reported in other human cancers. Given the dramatic response to ALK inhibition in this case, identifying patients with fusion MTC has important therapeutic implications.
甲状腺髓样癌 (MTC) 最常与 基因突变相关。融合已很少被描述，尽管以前在儿科中没有描述过，也没有与 MTC 或任何其他癌症相关联。一名 10 岁男孩出现进行性喘鸣，被诊断为转移性 MTC，包括肺、淋巴结和肾上腺转移。基线降钙素为 6703pg/mL。在进行分子检测时，他接受了试验性选择性 RET 抑制剂 LOXO-292 的经验性治疗，但没有改善。分子检测显示一种新的 - 融合。他的治疗方案改为克唑替尼，然后改为阿来替尼，以提高耐受性。ALK 抑制 6 天后，降钙素降至 663pg/mL。他继续接受阿来替尼治疗，反应持续。一种新的 - 融合现已被牵连到一例儿童转移性 MTC 中。这种融合对 ALK 抑制剂具有显著的临床敏感性。该报告扩展了 MTC 中观察到的 融合谱，包括首例儿童转移性 MTC。这种与 易位的 MTC 的新型融合以前没有在其他人类癌症中报道过。鉴于这种情况下对 ALK 抑制的显著反应，鉴定出具有 融合 MTC 的患者具有重要的治疗意义。
