靶碘联合：进展期分化型甲状腺癌治疗新策略

doi:10.16139/j.1007-9610.2023.06.06

摘要/Abstract

摘要：

进展期分化型甲状腺癌缺乏有效的治疗方案、总体预后较差，是临床亟需解决的难题。多靶点酪氨酸激酶抑制剂已获批应用于放射性碘难治性分化型甲状腺癌的治疗，最近也被推荐用于局部进展期分化型甲状腺癌术前新辅助治疗。虽然放射性碘治疗是进展期分化型甲状腺癌术后的标准治疗方案，但存在一定的局限性和限制。多靶点酪氨酸激酶抑制剂联合放射性碘治疗，有望成为进展期分化型甲状腺癌治疗的新策略。

关键词: 进展期分化型甲状腺癌, 多靶点激酶抑制剂, 放射性碘, 碘-131

Abstract:

Advanced differentiated thyroid carcinoma (ADTC) lacks effective treatment options, and has a poor prognosis, which is an urgent clinical problem to be resolved. Targeted multikinase inhibitor(MKI) has been approved for the treatment of radioiodine refractory differentiated thyroid carcinoma, and have recently been recommended as a preoperative neoadjuvant therapy agents for locally ADTC. Although radioiodine therapy is the standard postoperative treatment for ADTC, it has certain limitations. MKI combined with radioiodine therapy is expected to become a new strategy of treatment for ADTC.

Key words: Advanced differentiated thyroid carcinoma, Multikinase inhibitor, Radioiodine, ¹³¹I

中图分类号:

R736.1

柳卫. 靶碘联合：进展期分化型甲状腺癌治疗新策略[J]. 外科理论与实践, 2023, 28(06): 520-523.

LIU Wei. Combination of targeted multikinase inhibitor and radioiodine: a new strategy of treatment for advanced differentiated thyroid carcinoma[J]. Journal of Surgery Concepts & Practice, 2023, 28(06): 520-523.

图/表 1

参考文献 28

[1]	PIZZATO M, LI M, VIGNAT J, et al. The epidemiological landscape of thyroid cancer worldwide: GLOBOCAN estimates for incidence and mortality rates in 2020[J]. Lancet Diabetes Endocrinol, 2022, 10(4):264-272. doi: 10.1016/S2213-8587(22)00035-3 URL
[2]	ZENG H, CHEN W, ZHENG R, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries[J]. Lancet Glob Health, 2018, 6(5):e555-e567. doi: 10.1016/S2214-109X(18)30127-X pmid: 29653628
[3]	COCA-PELAZ A, RODRIGO J P, SHAH J P, et al. Recurrent differentiated thyroid cancer: the current treatment options[J]. Cancers (Basel), 2023, 15(10):2692. doi: 10.3390/cancers15102692 URL
[4]	HAUGEN B R, ALEXANDER E K, BIBLE K C, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer[J]. Thyroid, 2016, 26(1):1-133. doi: 10.1089/thy.2015.0020 URL
[5]	DURANTE C, HADDY N, BAUDIN E, et al. Long-term outcome of 444 patients with distant metastases from papi-llary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy[J]. J Clin Endocrinol Metab, 2006, 91(8):2892-2899. doi: 10.1210/jc.2005-2838 URL
[6]	RUEGEMER J J, HAY I D, BERGSTRALH E J, et al. Distant metastases in differentiated thyroid carcinoma: a multivariate analysis of prognostic variables[J]. J Clin Endocrinol Metab, 1988, 67(3):501-508. doi: 10.1210/jcem-67-3-501 URL
[7]	RATAJCZAK M, GAWEŁ D, GODLEWSKA M. Novel inhibitor-based therapies for thyroid cancer - an update[J]. Int J Mol Sci, 2021, 22(21):11829. doi: 10.3390/ijms222111829 URL
[8]	中国医师协会外科医师分会甲状腺外科医师委员会, 中国研究型医院学会甲状腺疾病专业委员会, 中国医疗保健国际交流促进会普通外科学分会, 等. 局部进展期甲状腺癌新辅助治疗中国专家共识(2023版)[J]. 中国实用外科杂志, 2023, 43(8):841-848.
	The Thyroid Surgeon Committee of the Surgical Branch of the Chinese Medical Association, The Thyroid Disease Professional Committee of the Chinese Research Hospital Association, The General Surgery Branch of the Chinese Healthcare International Exchange Promotion, et al. Association Chinese expert consensus on neoadjuvant therapy for locally advanced thyroid cancer (2023 version)[J]. Chin J Pract Surg, 2023, 43(8):841-848.
[9]	HAUGEN B R, SHERMAN S I. Evolving approaches to patients with advanced differentiated thyroid cancer[J]. Endocr Rev, 2013, 34(3):439-455. doi: 10.1210/er.2012-1038 pmid: 23575762
[10]	RUSSELL M D, KAMANI D, RANDOLPH G W. Modern surgery for advanced thyroid cancer: a tailored approach[J]. Gland Surg, 2020, 9(Suppl 2):S105-S119. doi: 10.21037/gs URL
[11]	SHONKA D C Jr, HO A, CHINTAKUNTLAWAR A V, et al. American head and neck society endocrine surgery section and international thyroid oncology group consensus statement on mutational testing in thyroid cancer: defining advanced thyroid cancer and its targeted treatment[J]. Head Neck, 2022, 44(6):1277-1300. doi: 10.1002/hed.v44.6 URL
[12]	NIXON I J, SIMO R, NEWBOLD K, et al. Management of invasive differentiated thyroid cancer[J]. Thyroid, 2016, 26(9):1156-1166. doi: 10.1089/thy.2016.0064 pmid: 27480110
[13]	FATOURECHI V, HAY I D, JAVEDAN H, et al. Lack of impact of radioiodine therapy in tg-positive, diagnostic whole-body scan-negative patients with follicular cell-derived thyroid cancer[J]. J Clin Endocrinol Metab, 2002, 87(4):1521-1526. doi: 10.1210/jcem.87.4.8373 URL
[14]	SABRA M M, GREWAL R K, TALA H, et al. Clinical outcomes following empiric radioiodine therapy in patients with structurally identifiable metastatic follicular cell-derived thyroid carcinoma with negative diagnostic but positive post-therapy ¹³¹I whole-body scans[J]. Thyroid, 2012, 22(9):877-883. doi: 10.1089/thy.2011.0429 URL
[15]	ILHAN H, MUSTAFA M, BARTENSTEIN P, et al. Rate of elimination of radioiodine-avid lymph node metastases of differentiated thyroid carcinoma by postsurgical radioiodine ablation. A bicentric study[J]. Nuklearmedizin, 2016, 55(6):221-227. pmid: 27588323
[16]	RONGA G, FILESI M, MONTESANO T, et al. Lung metastases from differentiated thyroid carcinoma. A 40 years' experience[J]. Q J Nucl Med Mol Imaging, 2004, 48(1):12-19.
[17]	BROSE M S, NUTTING C M, JARZAB B, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial[J]. Lancet, 2014, 384(9940):319-328. doi: 10.1016/S0140-6736(14)60421-9 pmid: 24768112
[18]	SCHLUMBERGER M, TAHARA M, WIRTH L J, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer[J]. N Engl J Med, 2015, 372(7):621-630. doi: 10.1056/NEJMoa1406470 URL
[19]	FALCHOOK G S, MILLWARD M, HONG D, et al. BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer[J]. Thyroid, 2015, 25(1):71-77. doi: 10.1089/thy.2014.0123 pmid: 25285888
[20]	Huang N S, Wei W J, Xiang J, et al. The efficacy and safety of anlotinib in neoadjuvant treatment of locally advanced thyroid cancer: a single-arm phase Ⅱ clinical trial[J]. Thyroid, 2021, 31(12):1808-1813. doi: 10.1089/thy.2021.0307 URL
[21]	OH J M, KALIMUTHU S, GANGADARAN P, et al. Reverting iodine avidity of radioactive-iodine refractory thyroid cancer with a new tyrosine kinase inhibitor (K905-0266) excavated by high-throughput NIS (sodium iodide symporter) enhancer screening platform using dual reporter gene system[J]. Oncotarget, 2018, 9(6):7075-7087. doi: 10.18632/oncotarget.24159 pmid: 29467951
[22]	SUZUKI K, IWAI H, UTSUNOMIYA K, et al. Efficacy of combination therapy with lenvatinib and radioactive iodine in thyroid cancer preclinical model[J]. Int J Mol Sci, 2022, 23(17):9872. doi: 10.3390/ijms23179872 URL
[23]	SUZUKI K, IWAI H, UTSUNOMIYA K, et al. Combination therapy with lenvatinib and radiation significantly inhibits thyroid cancer growth by uptake of tyrosine kinase inhibitor[J]. Exp Cell Res, 2021, 398(1):112390. doi: 10.1016/j.yexcr.2020.112390 URL
[24]	SHEU N W, JIANG H J, WU C W, et al. Lenvatinib complementary with radioiodine therapy for patients with advanced differentiated thyroid carcinoma: case reports and literature review[J]. World J Surg Oncol, 2019, 17(1):84. doi: 10.1186/s12957-019-1626-4
[25]	SHI L, YOU Q, WANG J, et al. Antitumour effects of apatinib in progressive, metastatic differentiated thyroid cancer (DTC)[J]. Endocrine, 2022, 78(1):68-76. doi: 10.1007/s12020-022-03113-9
[26]	DOTINGA M, VRIENS D, VAN VELDEN F H P, et al. Reinducing radioiodine-sensitivity in radioiodine-refractory thyroid cancer using lenvatinib (RESET): study protocol for a single-center, open label phase Ⅱ trial[J]. Diagnostics (Basel), 2022, 12(12):3154.
[27]	LIN Y S. The efficacy and safety of anlotinib hydrochloride or penpulimab in combination with RAI in patients with local advanced or metastatic differentiated thyroid cancer: a randomized, open-label, exploratory clinical trial[EB/OL]. [2023-10-08]. https://www.clinicaltrials.gov/study/NCT04952493 .
[28]	SONG H J, QIU X, HE Z, et al. The efficacy and safety of sequential use of anlotinib and ¹³¹I for locally advanced or metastatic differentiated thyroid cancer: a single-arm phase Ⅱ clinical trial[J]. J Clin Oncol, 2023, 41(16 suppl):e18102-e18102. doi: 10.1200/JCO.2023.41.16_suppl.e18102 URL

特征分类	特征描述
结构/外科	巨大、侵袭性或不可手术的原发颈部病灶、区域性转移或复发性疾病；远处转移包括纵隔转移；颈部残留病灶不适合再次手术；影像学表现为快速进展或倍增时间<6个月；肿瘤的生长即将造成威胁
生化	不摄取放射性碘或放射性碘治疗疗效不佳；TSH抑制的情况下（TSH<0.1 mU/L）疾病仍进展；甲状腺球蛋白(thyroglobulin, Tg)倍增时间<6个月
组织学/分子	分化差或侵袭性病理亚型（如柱状、高细胞、靴钉样等）；Ki-67指数高；高核分裂象计数/肿瘤坏死
临床判断	临床医师认定的其他侵袭性行为