Division of Pediatric Endocrinology, Department of Pediatrics, Mattel Children's Hospital, UCLA Medical Center, Los Angeles, CA, USA.
Division of Hematology Oncology, Department of Pediatrics, UCLA Medical Center, Los Angeles, CA, USA.
J Pediatr Endocrinol Metab. 2024 Sep 3;37(11):1009-1014. doi: 10.1515/jpem-2024-0281. Print 2024 Nov 26.
We introduced selpercatinib prior to radioactive iodine therapy prior to radioactive iodine therapy (RAI) for pediatric papillary thyroid cancer (PTC) to enhance the tumorical effects of RAI.
PTC has an excellent prognosis but is commonly associated with local and distant metastases. Successful complete response to the current standard of care, thyroidectomy with lymph node resection and RAI, is achieved in only a small minority of cases with metastases. The direct effect of tyrosine kinase inhibitors (TKIs) on tumor regression has been confirmed in several randomized controlled studies, while the increased RAI uptake has been reported in small case series, but typically TKIs are currently reserved third-line. Selpercatinib is a TKI that specifically has a durable effect in RET-fusion positive malignancies. We describe a 10-year-old Hispanic girl with metastatic PTC treated with total thyroidectomy and extensive lymph node resection. Evaluation for relevant genetic drivers of the malignancy revealed a strong overexpression of the RET tyrosine kinase domain indicative of a RET gene fusion. Selpercatinib 120 mg twice daily given orally was initiated prior to the initial dose of RAI to achieve further tumor regression by a direct cytostatic effect and then secondarily enhancement of RAI uptake. Minimal side effects occurred, specifically intermittent mild skin rashes that resolved. Resolution of distal lung metastases was noted on CT imaging. RAI was then administered 9 months afterward, with ultimately achievement of a low thyroglobulin level 1.0 ng/mL 11 months after RAI.
In conclusion, selpercatinib given prior to the initial dose of adjunctive RAI for RET-fusion positive PTC is a well-tolerated intervention that further reduces tumor burden and potentially enhances the tumorcidal effects of RAI.
我们在放射性碘治疗（RAI）之前引入塞普替尼（selpercatinib）用于儿科甲状腺乳头状癌（PTC），以增强 RAI 的肿瘤效应。
PTC 预后良好，但常伴有局部和远处转移。通过甲状腺切除术和淋巴结切除术联合 RAI 的当前标准治疗方案，仅有少数伴有转移的患者能够获得完全缓解。几项随机对照研究证实了酪氨酸激酶抑制剂（TKI）对肿瘤消退的直接作用，而小系列病例报告显示 RAI 摄取增加，但 TKI 通常保留在三线治疗。塞普替尼是一种针对 RET 融合阳性恶性肿瘤具有持久疗效的 TKI。我们描述了一位 10 岁的西班牙裔女孩，患有转移性 PTC，接受了全甲状腺切除术和广泛的淋巴结切除术。对恶性肿瘤相关遗传驱动因素的评估显示，RET 酪氨酸激酶结构域的强烈过表达表明存在 RET 基因融合。在开始给予 RAI 初始剂量之前，给予患者塞普替尼 120mg 每日两次口服，以通过直接细胞抑制作用进一步实现肿瘤消退，然后继发增强 RAI 摄取。仅出现轻微副作用，特别是间歇性轻度皮疹，可自行缓解。CT 成像显示远端肺转移灶已消退。9 个月后给予 RAI，最终在 RAI 后 11 个月达到低甲状腺球蛋白水平 1.0ng/mL。
总之，在给予辅助 RAI 的初始剂量之前，给予 RET 融合阳性 PTC 患者塞普替尼是一种耐受良好的干预措施，可进一步降低肿瘤负担，并可能增强 RAI 的肿瘤杀伤作用。
