Faculty of Health and Medicine, University of Sydney, Sydney 2006, Australia.
Department of Diabetes and Endocrinology, Royal North Shore Hospital, Sydney 2065, Australia.
Endocr Rev. 2023 Sep 15;44(5):934-946. doi: 10.1210/endrev/bnad013.
A personalized approach to the management of medullary thyroid cancer (MTC) presents several challenges; however, in the past decade significant progress has been made in both diagnostic and treatment modalities. Germline rearranged in transfection (RET) testing in multiple endocrine neoplasia 2 and 3, and somatic RET testing in sporadic MTC have revolutionized the treatment options available to patients. Positron emission tomography imaging with novel radioligands has improved characterization of disease and a new international grading system can predict prognosis. Systemic therapy for persistent and metastatic disease has evolved significantly with targeted kinase therapy especially for those harboring germline or somatic RET variants. Selpercatinib and pralsetinib are highly selective RET kinase inhibitors that have shown improved progression-free survival with better tolerability than outcomes seen in earlier multikinase inhibitor studies. Here we discuss changes in paradigms for MTC patients: from determining RET alteration status upfront to novel techniques for the evaluation of this heterogenous disease. Successes and challenges with kinase inhibitor use will illustrate how managing this rare malignancy continues to evolve.
对甲状腺髓样癌（MTC）的管理采用个性化方法会带来一些挑战；然而，在过去十年中，在诊断和治疗方式方面取得了重大进展。多发性内分泌肿瘤 2 型和 3 型中的种系重排转染（RET）检测，以及散发性 MTC 中的体细胞 RET 检测，彻底改变了患者的治疗选择。新型放射性配体的正电子发射断层扫描成像改善了疾病的特征，新的国际分级系统可以预测预后。对于持续性和转移性疾病的全身治疗已经发生了重大变化，靶向激酶治疗，特别是针对那些具有种系或体细胞 RET 变体的患者。Selpercatinib 和 pralsetinib 是高度选择性的 RET 激酶抑制剂，与早期多激酶抑制剂研究相比，它们显示出了更好的无进展生存期和更好的耐受性。在这里，我们讨论了 MTC 患者的治疗模式的变化：从确定 RET 改变状态到评估这种异质性疾病的新方法。激酶抑制剂使用的成功和挑战将说明如何继续发展这种罕见的恶性肿瘤的管理。
