可疑甲状腺球蛋白增高性分化型甲状腺癌患者经131I治疗后的临床转归

doi:10.19401/j.cnki.1007-3639.2022.05.006

中国癌症杂志 ›› 2022, Vol. 32 ›› Issue (5): 410-416.doi: 10.19401/j.cnki.1007-3639.2022.05.006

可疑甲状腺球蛋白增高性分化型甲状腺癌患者经¹³¹I治疗后的临床转归

郭文婷¹()(), 慕转转²^,³, 李征²^,⁴, 张迎强²^,³, 靳晓娜²^,³, 林岩松²^,³()()

1.中国医学科学院北京协和医学院北京协和医院医学科学研究中心,疑难重症及罕见病国家重点实验室,北京 100730
2.中国医学科学院北京协和医学院北京协和医院核医学科,疑难重症及罕见病国家重点实验室,北京 100730
3.核医学分子靶向诊疗北京市重点实验室,北京 100730
4.北京核工业医院核素诊疗中心,北京 102413

收稿日期:2022-04-18 修回日期:2022-05-02 出版日期:2022-05-30 发布日期:2022-06-09
通信作者: 林岩松 E-mail:wtcandy@126.com;linyansong1968@163.com
作者简介:郭文婷（ORCID: 0000-0002-9097-2828）,博士,研究实习员 E-mail: wtcandy@126.com
基金资助:
国家重点研发计划“政府间国际科技创新合作/港澳台科技创新合作”重点专项(2019YFE0106400);中国医学科学院中央级公益性科研院所基本科研业务费专项资金(2019XK320009);中国医学科学院医学与健康科技创新工程(2020-I2M-2-003)

Clinical outcome of ¹³¹I therapy in differentiated thyroid cancer patients with suspicious high thyroglobulin concentration

GUO Wenting¹()(), MU Zhuanzhuan²^,³, LI Zheng²^,⁴, ZHANG Yingqiang²^,³, JIN Xiaona²^,³, LIN Yansong²^,³()()

1. Department of Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
2. Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
3. Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing 100730, China
4. Department of Radionuclide Treatment Center, Beijing Nuclear Industry Hospital, Beijing 102413, China

Received:2022-04-18 Revised:2022-05-02 Published:2022-05-30 Online:2022-06-09
Contact: LIN Yansong E-mail:wtcandy@126.com;linyansong1968@163.com

摘要/Abstract

摘要：

背景与目的： 分化型甲状腺癌（differentiated thyroid cancer,DTC）中可疑甲状腺球蛋白（thyroglobulin,Tg）水平增高但无明确结构性病灶者预后差异大,临床治疗决策存在较大争议,本研究拟探究¹³¹I治疗及不同治疗剂量对于这类患者临床转归的影响。方法： 回顾并分析2007—2021年就诊于北京协和医院核医学科的138例DTC全切术后可疑Tg水平增高的患者,依据首次¹³¹I治疗剂量分为低（剂量为1.11 GBq）、中（1.11 GBq<剂量≤3.70 GBq）、高（3.70 GBq<剂量≤7.40 GBq）3组,观察不同剂量¹³¹I治疗后6个月的短期及后续未再行其他干预患者的长期疗效,并进一步观察经初始治疗评估为生化疗效不佳（biochemical incomplete response,BIR）患者的临床转归。采用受试者工作特征（receiver operating characteristic,ROC）曲线评估预测结构性疗效不佳（structural incomplete response,SIR）和远处转移的刺激性Tg（stimulated Tg,sTg）的最佳界值点。结果： 低、中、高3个剂量组中分别有6.7%、13.5%、7.0%的患者短期疗效达到疗效满意（excellent response,ER）,3组间总体疗效差异无统计学意义（H=1.02,P=0.60）。常规随访下3组患者的长期疗效同样差异无统计学意义（H=2.94,P=0.23）。经初始治疗评估为BIR的患者经常规随访和再次¹³¹I治疗后的临床转归差异无统计学意义（U=324.5,P=0.15）。预测SIR和远处转移的sTg最佳界值点分别为27.5和61.7 ng/mL。结论： 可疑Tg水平增高的DTC患者复发率较高,以27.5 ng/mL为sTg界值点有助于尽早识别这部分患者。¹³¹I治疗有助于术后可疑Tg水平增高患者快速达到ER,但高剂量¹³¹I治疗未对患者的预后产生增益效应;再次¹³¹I治疗对于BIR患者未显示出进一步获益。

关键词: 分化型甲状腺癌, 甲状腺球蛋白, ¹³¹I治疗, 生化疗效不佳

Abstract:

Background and purpose: The prognosis of differentiated thyroid cancer (DTC) patients with suspicious high thyroglobulin (Tg) concentration and without explicit structural lesions varies from each other, hence the clinical treatment decisions including ¹³¹I therapy remain controversial. This study aimed to explore the effects of ¹³¹I treatment and the therapeutic dose on the clinical outcome of these patients. Methods: The study included 138 DTC patients treated in Department of Nuclear Medicine, Peking Union Medical College Hospital from 2007 to 2021, who had undergone total thyroidectomy and subsequent ¹³¹I therapy. All patients were divided into 3 groups as low dose (dose=1.11 GBq), medium dose (1.11 GBq<dose≤3.70 GBq) and high dose (3.70 GBq<dose≤7.40 GBq) according to the dose of ¹³¹I therapy. We compared the short-term and end-of period response to therapy among these three groups, and further observed the clinical outcome of patients with biochemical incomplete response (BIR) after initial treatment. The receiver operating characteristic (ROC) curve was employed to evaluate the predictive value of stimulated Tg (sTg) levels in patients with structural incomplete response (SIR) and distant metastasis. Results: For the short-term response, the rate of excellent response (ER) was 6.7%, 13.5% and 7.0% in low, medium and high dose group, respectively. The short-term response showed no statistically significant difference among three groups (H=1.02, P=0.60). The end-of-period response among the three groups under routine follow-up also showed no significant difference (H=2.94, P=0.23). No significant difference was observed in the clinical outcome of patients with BIR after routine follow-up and second ¹³¹I treatment (U=324.5, P=0.15). The diagnostic critical point (DCP) of sTg to predict SIR and distant metastasis was 27.5 and 61.7 ng/mL, respectively. Conclusion: DTC patients with suspicious high Tg concentration has high recurrence risk, taking 27.5 ng/mL as the cut-off of sTg is helpful to identify the patients with high recurrence risk early. ¹³¹I treatment is helpful for these patients to achieve ER as soon as possible. However, high-dose ¹³¹I did not have greater benefits on the prognosis of these patients. Second ¹³¹I treatment showed no further benefit for BIR patients.

Key words: Differentiated thyroid cancer, Thyroglobulin, ¹³¹I therapy, Biochemical incomplete response

中图分类号:

R736.1

郭文婷, 慕转转, 李征, 张迎强, 靳晓娜, 林岩松. 可疑甲状腺球蛋白增高性分化型甲状腺癌患者经¹³¹I治疗后的临床转归[J]. 中国癌症杂志, 2022, 32(5): 410-416.

GUO Wenting, MU Zhuanzhuan, LI Zheng, ZHANG Yingqiang, JIN Xiaona, LIN Yansong. Clinical outcome of ¹³¹I therapy in differentiated thyroid cancer patients with suspicious high thyroglobulin concentration[J]. China Oncology, 2022, 32(5): 410-416.

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参考文献 13

[1]	TUTTLE R M, LEBOEUF R. Follow up approaches in thyroid cancer: a risk adapted paradigm[J]. Endocrinol Metab Clin N Am, 2008, 37(2): 419-435,, ix-x. doi: 10.1016/j.ecl.2008.02.008
[2]	TUTTLE R M, TALA H, SHAH J, et al. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system[J]. Thyroid, 2010, 20(12): 1341-1349. doi: 10.1089/thy.2010.0178
[3]	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
[4]	丁勇, 马庆杰, 王任飞, 等. 分化型甲状腺癌术后¹³¹I治疗前评估专家共识[J]. 中国癌症杂志, 2019, 29(10): 832-840.
	DING Y, MA Q J, WANG R F, et al. Expert consensus on preoperative evaluation of ¹³¹I after surgery for differentiated thyroid cancer[J]. China Oncol, 2019, 29(10): 832-840.
[5]	ALZAHRANI A S, MOHAMED G, AL SHAMMARY A, et al. Long-term course and predictive factors of elevated serum thyroglobulin and negative diagnostic radioiodine whole body scan in differentiated thyroid cancer[J]. J Endocrinol Invest, 2005, 28(6): 540-546. doi: 10.1007/BF03347243
[6]	CASTAGNA M G, TALA JURY H P, CIPRI C, et al. The use of ultrasensitive thyroglobulin assays reduces but does not abolish the need for TSH stimulation in patients with differentiated thyroid carcinoma[J]. J Endocrinol Invest, 2011, 34(8): e219-e223.
[7]	VAISMAN F, MOMESSO D, BULZICO D A, et al. Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy[J]. Clin Endocrinol (Oxf), 2012, 77(1): 132-138. doi: 10.1111/j.1365-2265.2012.04342.x
[8]	SZUMOWSKI P, ABDELRAZEK S, IWANICKA D, et al. Dosimetry during adjuvant ¹³¹I therapy in patients with differentiated thyroid cancer-clinical implications[J]. Sci Rep, 2021, 11(1): 13930. doi: 10.1038/s41598-021-93431-1
[9]	CAMPENNÌ A, GIOVANELLA L, PIGNATA S A, et al. Thyroid remnant ablation in differentiated thyroid cancer: searching for the most effective radioiodine activity and stimulation strategy in a real-life scenario[J]. Nucl Med Commun, 2015, 36(11): 1100-1106. doi: 10.1097/MNM.0000000000000367
[10]	YANG X, LIANG J, LI T J, et al. Preablative stimulated thyroglobulin correlates to new therapy response system in differentiated thyroid cancer[J]. J Clin Endocrinol Metab, 2016, 101(3): 1307-1313. doi: 10.1210/jc.2015-4016
[11]	YANG X, LIANG J, LI T J, et al. Postoperative stimulated thyroglobulin level and recurrence risk stratification in differentiated thyroid cancer[J]. Chin Med J (Engl), 2015, 128(8): 1058-1064.
[12]	TUTTLE R M. Optimal management of a biochemical incomplete response to therapy in differentiated thyroid cancer: aggressive treatment or cautious observation?[J]. Endocrine, 2014, 46(3): 363-364. doi: 10.1007/s12020-014-0213-2
[13]	慕转转, 李征, 张鑫, 等. 经验性¹³¹I治疗对甲状腺乳头状癌不摄碘肺转移患者价值存疑[J]. 中国癌症杂志, 2020, 30(12): 991-995.

Characteristic	Low dose group	Medium dose group	High dose group	Statistics value	P value
Gender n (%)				χ²=0.94	0.63
Male	4 (26.6)	15 (40.5)	30 (34.8)
Female	11 (73.4)	22 (59.5)	56 (65.2)
Age/year median (P25, P75)	36.0 (33.5, 41.5)	36.0 (30.0, 44.0)	33.5 (28.3, 38.0)	H=3.09	0.21
T staging n (%)				H=4.95	0.08
T_1a	6 (40.0)	11 (29.7)	26 (30.2)
T_1b	8 (53.3)	12 (32.4)	22 (25.5)
T₂	0 (0.0)	9 (24.3)	17 (19.7)
T_3a	0 (0.0)	0 (0.0)	2 (2.3)
T_3b	0 (0.0)	1 (2.7)	4 (4.6)
T_4a	0 (0.0)	3 (8.1)	11 (12.7)
T_x	1 (6.6)	1 (2.7)	4 (4.6)
N staging n (%)				H=7.88	0.02
N₀	2 (13.3)	1 (2.7)	3 (3.5)
N_1a	7 (46.6)	13 (35.1)	21 (24.5)
N_1b	5 (33.3)	23 (62.1)	62 (72.0)
N_x	1 (6.6)	0 (0.0)	0 (0.0)
Capsular involvement n (%)				χ²=3.12	0.21
Yes	8 (53.3)	15 (40.5)	52 (60.4)
No	6 (40.0)	9 (24.3)	16 (18.6)
Unknown	1 (6.6)	13 (35.1)	18 (21.0)
Multifocality n (%)				χ²=0.33	0.85
Yes	9 (60.0)	15 (40.5)	32 (37.2)
No	4 (26.6)	7 (20.0)	11 (12.7)
Unknown	2 (13.3)	15 (40.5)	43 (50.0)
BRAF status n (%)				χ²=2.35	0.31
Mutant	6 (40.0)	9 (24.3)	19 (22.1)
Wild type	0 (0.0)	4 (10.8)	5 (5.8)
Unknown	9 (60.0)	24 (64.8)	62 (72.1)
sTg level ρ_B/(ng·mL^-1) median (P25, P75)	26.6 (13.0, 46.6)	26.2 (14.0, 64.0)	29.8 (20.4, 58.0)	H=1.61	0.45

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可疑甲状腺球蛋白增高性分化型甲状腺癌患者经¹³¹I治疗后的临床转归

Clinical outcome of ¹³¹I therapy in differentiated thyroid cancer patients with suspicious high thyroglobulin concentration

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