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.

中文翻译：

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甲状腺髓样癌：更新和挑战。

甲状腺髓样癌 (MTC) 的个性化治疗方法面临着一些挑战；然而，在过去十年中，诊断和治疗方式都取得了重大进展。多发性内分泌肿瘤 2 和 3 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可用的治疗选择。使用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，并且新的国际分级系统可以预测预后。随着靶向激酶疗法的发展，针对持续性和转移性疾病的全身治疗已取得显着进展，特别是对于那些携带种系或体细胞 RET 变异的疾病。Selpercatinib 和 pralsetinib 是高选择性 RET 激酶抑制剂，与早期多激酶抑制剂研究中观察到的结果相比，它们显示出改善的无进展生存期和更好的耐受性。在这里，我们讨论 MTC 患者范式的变化：从预先确定 RET 改变状态到评估这种异质性疾病的新技术。使用激酶抑制剂的成功和挑战将说明治疗这种罕见恶性肿瘤的方法如何继续发展。