摘要
局部进展期甲状腺癌（LATC）占甲状腺癌的5%～15%，常累及周围重要神经、血管和器官，导致手术切除困难及预后不良。其组织学类型包括甲状腺乳头状癌、滤泡癌、嗜酸细胞癌、低分化癌（PDTC）、甲状腺未分化癌（ATC）及高级别甲状腺髓样癌（MTC）。分子学层面，BRAF、RAS、RET等驱动基因激活以及TP53、TERT启动子突变与其高侵袭性密切相关。新辅助治疗作为新兴策略，旨在通过术前药物治疗实现肿瘤降期，提高可切除率，改善功能保留并延长生存。多靶点酪氨酸激酶抑制剂（mTKI）如安罗替尼、仑伐替尼，以及高选择性靶向药物如RET抑制剂（塞普替尼、普拉替尼）在LATC新辅助治疗中显示较高客观缓解率（ORR），部分病例实现R0切除。对于BRAF V600E突变的ATC，达拉非尼联合曲美替尼的术前治疗显著改善生存。免疫治疗方面，程序性死亡受体1（PD-1）/程序性死亡配体1（PD-L1）抑制剂单用或联合靶向治疗在ATC和PDTC中展现潜力。尽管疗效证据逐渐积累，但不良反应及最佳用药时机尚需进一步探索。未来应依托多中心临床研究，建立基于分子分型的个体化新辅助治疗体系，推动LATC向精准化和规范化治疗发展。
Abstract
Locally advanced thyroid carcinoma (LATC) accounts for 5%-15% of thyroid cancers and often involves adjacent critical nerves, vessels, and organs, resulting in surgical challenges and poor prognosis. Histologic subtypes include papillary thyroid carcinoma, follicular carcinoma, oncocytic carcinoma, poorly differentiated thyroid carcinoma (PDTC), anaplastic thyroid carcinoma (ATC), and high-grade medullary thyroid carcinoma (MTC).At the molecular level, activation of driver genes such as BRAF, RAS, and RET, together with mutations in TP53 and the TERT promoter, is closely associated with the aggressive behavior of LATC. Neoadjuvant therapy has emerged as a novel strategy, aiming to downstage tumors preoperatively, increase resectability, improve functional preservation, and prolong survival. Multitarget tyrosine kinase inhibitors (mTKIs), such as anlotinib and lenvatinib, and highly selective targeted agents, such as RET inhibitors (selpercatinib and pralsetinib), have demonstrated high objective response rates (ORR)in LATC neoadjuvant therapy, with some cases achieving R0 resection. For ATC with BRAF V600E mutation, preoperative therapy with dabrafenib plus trametinib has significantly improved survival. In the field of immunotherapy, programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors, either as monotherapy or in combination with targeted therapy, have shown potential efficacy in ATC and PDTC. Although evidence of efficacy is accumulating, optimal timing and management of adverse effects remain to be clarified. Future multicenter clinical studies are needed to establish individualized neoadjuvant therapy systems based on molecular subtyping, thereby advancing LATC toward precision and standardized treatment.
关键词
局部进展期甲状腺癌 /
新辅助治疗 /
靶向治疗 /
免疫治疗
Key words
local advanced thyroid cancer /
neoadjuvant Treatment /
target therapy /
immunotherapy
陈嘉莹, 王 宇.
新辅助治疗在局部进展期甲状腺癌中应用[J]. 中国实用外科杂志. 2025, 45(09): 1005-1011 https://doi.org/10.19538/j.cjps.issn1005-2208.2025.09.08
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