-
近年来, 甲状腺癌的发病率呈明显上升趋势, 并有年轻化的倾向, 部分患者以转移为首发症状。分化型甲状腺癌(differentiated thyroid carcinoma, DTC)术后采用131I清除残留功能性甲状腺组织(清甲)及可能残留的转移癌灶, 可降低复发率、提高生存率、提高DTC转移灶或复发病灶的治疗疗效、提高随访监测方法的诊断灵敏度和准确性。131I清甲治疗较适用于以下DTC患者[1]:年龄大于45岁; 癌灶有肉眼可见的甲状腺外浸润; 瘤体直径大于1~2 cm或已侵犯包膜; 有多发或双侧淋巴结转移受累; 有远处转移。清甲治疗所选的131I剂量为1.11~3.70 GBq。本文主要从与131I清甲治疗方法相关的问题进行阐述。
-
1998年rhTSH在美国进入临床应用, 2001年普及至欧洲。rhTSH开始主要应用于DTC患者的诊断与随访, 随后逐渐应用到DTC术后131I清甲的辅助治疗[2]。目前, DTC术后无论使用高剂量(3.7 GBq)还是低剂量(1.1 GBq)131I清甲, 均有在清甲前应用rhTSH的报道[3-4]。
正常甲状腺滤泡上皮和DTC细胞的胞膜上表达钠碘同向转运体, 在TSH刺激下可充分摄取131I, 因此残余甲状腺组织及残留转移病灶的消除均需要TSH的刺激, 当血清TSH在131I清甲治疗前升高至大于30 mU/L时, 可显著增加DTC的肿瘤组织对131I的摄取。大部分患者停服甲状腺素3~4周后, 可使内源性TSH水平逐渐升高至30 mU/L或以上。但对于停服甲状腺素的患者, 因造成了甲状腺功能减退症(甲减), 使患者的生活质量、工作能力有所下降, 甚至造成其认知损害、情感障碍等一系列的甲减症状。另外, TSH的持续高水平会导致其潜在的全身疾病加重, 并可能会导致激素降低后肿瘤生长速度的加快, 并使人体血液中摄入的131I剂量增加[5-6]。应用rhTSH后, TSH可迅速升高, 其与停服甲状腺素效果类似, 但可避免甲状腺激素降低后甲减的发生, 改善了患者的生活质量, 对于老年DTC患者、部分不能忍受甲减和因伴有下丘脑、垂体等病变不能产生足够TSH的患者尤为适用。
rhTSH辅助131I清甲方案为:甲状腺激素替代期间连续2 d肌内注射rhTSH, 0.9 mg/d, 第3日行131I治疗。131I清甲治疗后1周行全身显像, 以了解残余甲状腺情况及探查是否有其他摄碘功能的转移灶[7]。
有文献报道, 在rhTSH辅助131I清甲的患者中, 全身器官及血液中131I的清除时间较停药组短, 从而可能导致病灶的摄碘率乃至吸收剂量降低[8]。因此有学者认为, 使用rhTSH时, 应适当增加131I清甲的剂量[9], 但迄今为止的临床数据表明, 残留甲状腺组织吸收131I的剂量与临床、生化代谢之间的联系仍未完全清楚, 因此认为这种做法是不必要的[9-10]。清除时间的增快也可能使rhTSH使用的安全性、便利性得以提高, 如减少甲状腺外区域暴露在辐射中、缩短住院时间等。Rosario等[11]研究亦发现, 与停药组相比, rhTSH辅助治疗可降低甲状腺床外131I的摄取, 从而减少唾液腺、性腺、血液系统的损害以及降低了氧化损伤的程度。由于人体血液中摄入的131I剂量减少, rhTSH的应用甚至可以降低131I清甲治疗诱导发生的部分染色体的畸变率, 从而提高131I治疗的安全性[12]。
表 1为近年来有关rhTSH辅助与停服甲状腺素后131I清甲疗效对比的前瞻性研究。从总体概括, 两者的清甲疗效差异不明显。但Pacini等[3]对162例患者进行的非随机性前瞻性研究发现, rhTSH辅助清甲成功率比Rosario等[11]报道的稍低, rhTSH并未提高成功率, 这可能与病例的非随机分组有关, 且rhTSH可能加快了131I的清除, 导致131I生物利用度的降低。但Pacini等[4]后来完成的一项国际多中心随机对照研究发现, 当131I剂量为3700 MBq时, rhTSH与停药组的清甲成功率相当, 且使用rhTSH的患者生活质量评分较停药组高。Barbaro等[13]考虑到L-甲状腺素代谢产生的碘可能会影响rhTSH的生物作用而降低131I清甲的疗效, 从而把DTC全切术后患者分为停药组及rhTSH+短暂停药组, 治疗1年后发现二者的清除率无明显差异。另外, Tuttle等[8]对394例清甲后的患者随访2.5年发现, rhTSH组与停药组的复发率相似(分别为4%和7%)。另一项对患者进行长期随访的研究也表明, 两组的长期复发率(最短随访时间为5年)、肿瘤标志物(甲状腺球蛋白、甲状腺球蛋白抗体)的变化均无明显差异, 表明行DTC全切术后, 使用rhTSH与停服甲状腺素相比, 是一种有效的辅助131I清甲方法[14]。更大规模、更广泛的多中心随机对照临床研究以及更长远的随访观察有待展开, 以研究其应用对长远复发率及生存率的影响, 为rhTSH辅助131I清甲的疗效提供更有力的证据。
文献源 年份 组别 患者例数 131I剂量(MBq) 清甲成功率(%) dxDBS Tg [3] 2002 停药组 50 1100 84.0 88.0 rhTSH组 70 1100 54 74.1 rhTSH+停药组 42 1100 78.5 95.0 [13] 2003 停药组 24 1100 75 75 rhTSH+短暂停药组a 16 1100 87.6 81.2 [4] 2006 停药组 28 3700 86 86 rhTSH组 32 3700 75 96 [15] 2006 停药组 41 1100 75.6 78 rhTSH组 52 1100 76.9 86.5 [8] 2008 停药组 71 3811 76 - rhTSH组 220 4033 83 - [11] 2008 停药组 64 3700 80b - rhTSH组 30 3700 90 - [16] 2019 停药组 36 3700 91 97 rhTSH组 36 3700 72 92 [17] 2013 停药组 50 1100 74c - rhTSH组 70 1100 67.1 - rhTSH+停药组 39 1100 76.2 - 注:表中,停药:131I清甲治疗前停服甲状腺素;rhTSH:重组人促甲状腺激素;dxDBS:诊断性全身显像;Tg:甲状腺球蛋白;a:rhTSH注射前停服甲状腺素4 d,131I治疗后重新口服甲状腺激素;b:TSH刺激下Tg < 1 ng/ml,颈部超声未探及异常;c:TSH刺激下Tg < 1 ng/ml,甲状腺球蛋白抗体阴性,颈部超声未探及异常。 表 1 rhTSH与停服甲状腺素后131I清甲疗效对比
Table 1. A comparison between recombinant human thyroid stimulating hormone and levothyroxine withdrawal for radioactive iodine ablation of thyroid remnants
-
DTC术后进行131I清甲治疗, 其中碘剂量的选择一直是研究讨论的热点。治疗剂量的不同不仅关系到清甲的成功率, 还与甲状腺癌患者的转移率、复发率和生存时间密切相关。2009美国甲状腺协会(ATA)[19]、2010美国国家综合癌症网(NCCN)[28]、2012甲状腺结节和分化型甲状腺癌诊治指南[1]及2010欧洲肿瘤内科学会指南[29]均提出清甲治疗中使用131I的剂量为1100~3700 MBq, 临床医生可根据患者情况做出合适的选择。目前, 首次清甲治疗多数采用固定剂量法, 即3700 MBq的131I; 部分非高危患者采用低于3700 MBq的131I清甲, 如伴有淋巴结、肺及全身转移时则剂量酌情增加。虽然一直认为, 随着131I剂量的增加, 清甲成功率也在提高[30], 但其不良反应、并发症和潜在致病的风险亦可能随之上升。与高剂量131I治疗相比, 低剂量131I可能有较低的肿瘤复发率及降低永久性口干的发生、减少住院及隔离时间、减轻治疗费用等优势[31]。
已有部分回顾性研究或随机研究提出[32-36]:低剂量(1073~1850 MBq) 131I同样能达到高剂量131I的清甲效果, 但因其样本量较小、统计方法不恰当而受到质疑。究竟是否应采用低剂量131I进行清甲治疗?其治疗效果、不良反应与高剂量131I的差别如何?表 2汇总了一些前瞻性临床研究结果, 由于各中心研究设计类型、入选病例的手术方式、病理分期、清甲评价标准等方面的差异可造成清甲成功率的不同, 但从总体分析, 1100 MBq 131I联合rhTSH的清甲效果与3700 MBq 131I清除残余甲状腺组织的成功率并无明显差别。2012年, Mallick等[37]完成了首项多中心随机对照研究, 结果显示:清甲治疗后6个月, 经rhTSH刺激下Tg测定和131I全身骨显像证实, 低剂量与高剂量131I治疗疗效一致, 且联合使用rhTSH时, 1100 MBq 131I清甲能使患者的隔离时间达到最低。同时Schlumberger等[38]也得到了类似的研究结果。两种不同剂量131I清甲治疗后患者的生活质量相似, 但低剂量治疗期间及治疗后的不良反应相对更少, 如今已越来越倾向于给予患者低剂量131I治疗[37-39]。但在治疗时需注意治疗前评估, 如残留甲状腺体积较大及有微小转移灶时, 高剂量131I则更有效[40]。
文献源 年份 研究类型 不同治疗剂量患者例数 随访时间(月) 清甲有效标准 清甲成功率(%) TSH提高方法 1100MBq 3700MBq 1100MBq 3700MBq [39] 2008 单中心随机研究 81 77 18~77 吸碘率=0,Tg臆1.0 ng/ml 52.0 56.0 停药 [41] 2012 单中心随机研究 171 170 12 吸碘率=0,Tg < 2.0 ng/ml,TgAb < 100 IU/ml 41.5 68.8 停药 [37] 2012 多中心随机研究 214 207 6~9 吸碘率 < 0.1%,Tg < 2.0 ng/ml 85.0 88.9 停药或rhTSH [38] 2012 多中心随机研究 347 337 6~10 吸碘率=0,甲状腺超声正常,Tg臆1.0 ng/ml 91.2 93.4 停药或rhTSH 注:表中,Tg:甲状腺球蛋白;TgAb:甲状腺球蛋白抗体;rhTSH:重组人促甲状腺激素。 表 2 1100 MBq与3700 MBq131I清甲疗效比较
Table 2. Effect comparison between 131I ablation of thyroid remnants of 1100 MBq and 3700 MBq
在上述研究中, 中位随访时间最长的为51个月[39], 肿瘤的复发病例较少, 低剂量与高剂量131I清甲后的甲状腺癌复发率近似, 随访过程中甲状腺球蛋白和131I诊断性全身显像的阴性率亦无明显差异(84%和82%)。为进一步探讨低剂量131I清甲方法的利弊, 明确其适用范围及了解其对病情进展的影响, 更大规模的长期随访的多中心随机临床研究有待进一步开展, 以更好地推广其临床应用。
分化型甲状腺癌术后131I清甲治疗方法的相关问题
Issues related to radioactive iodine ablation in patients with differentiated thyroid carcinoma undergoing thyroid surgery
-
摘要: 分化型甲状腺癌(DTC)是最常见的甲状腺恶性肿瘤, 其中包括乳头状甲状腺癌、滤泡状甲状腺癌和混合型甲状腺癌。治疗方法有手术治疗、131I治疗和内分泌治疗。其中131I治疗是甲状腺癌重要的治疗环节或步骤。随着对DTC术后131I治疗方案的不断研究与探索, 在重组人促甲状腺激素辅助131I清甲的应用、131I清除大量残留的甲状腺叶组织、131I清甲治疗碘剂量的选择等方面的认识与实践也不断更新。该文就以上几个清甲治疗方法的研究进行综述。Abstract: Differentiated thyroid carcinoma(DTC)is the most common malignant tumor of thyroid gland, including papillary thyroid carcinoma, follicular thyroid carcinoma and the mixed type. Treatment methods include surgery, radioactive iodine treatment and endocrine treatment, in which radioactive iodine treatment for thyroid carcinoma is an important part of the treatment or procedure. With the ongoing research and exploration of radiation treatment, the recombinant human thyroid stimulating hormone assisted in radioactive iodine ablation of thyroid remnants, radioactive iodine to remove a lot of residual thyroid tissue, the radioactive iodine dose selection and other aspects of knowledge and practice are constantly updated. This paper summarizes recent progess in the radioactive iodine ablation.
-
Key words:
- Thyroid neoplasms /
- Iodine radioisotopes /
- Thyrotropin
-
表 1 rhTSH与停服甲状腺素后131I清甲疗效对比
Table 1. A comparison between recombinant human thyroid stimulating hormone and levothyroxine withdrawal for radioactive iodine ablation of thyroid remnants
文献源 年份 组别 患者例数 131I剂量(MBq) 清甲成功率(%) dxDBS Tg [3] 2002 停药组 50 1100 84.0 88.0 rhTSH组 70 1100 54 74.1 rhTSH+停药组 42 1100 78.5 95.0 [13] 2003 停药组 24 1100 75 75 rhTSH+短暂停药组a 16 1100 87.6 81.2 [4] 2006 停药组 28 3700 86 86 rhTSH组 32 3700 75 96 [15] 2006 停药组 41 1100 75.6 78 rhTSH组 52 1100 76.9 86.5 [8] 2008 停药组 71 3811 76 - rhTSH组 220 4033 83 - [11] 2008 停药组 64 3700 80b - rhTSH组 30 3700 90 - [16] 2019 停药组 36 3700 91 97 rhTSH组 36 3700 72 92 [17] 2013 停药组 50 1100 74c - rhTSH组 70 1100 67.1 - rhTSH+停药组 39 1100 76.2 - 注:表中,停药:131I清甲治疗前停服甲状腺素;rhTSH:重组人促甲状腺激素;dxDBS:诊断性全身显像;Tg:甲状腺球蛋白;a:rhTSH注射前停服甲状腺素4 d,131I治疗后重新口服甲状腺激素;b:TSH刺激下Tg < 1 ng/ml,颈部超声未探及异常;c:TSH刺激下Tg < 1 ng/ml,甲状腺球蛋白抗体阴性,颈部超声未探及异常。 表 2 1100 MBq与3700 MBq131I清甲疗效比较
Table 2. Effect comparison between 131I ablation of thyroid remnants of 1100 MBq and 3700 MBq
文献源 年份 研究类型 不同治疗剂量患者例数 随访时间(月) 清甲有效标准 清甲成功率(%) TSH提高方法 1100MBq 3700MBq 1100MBq 3700MBq [39] 2008 单中心随机研究 81 77 18~77 吸碘率=0,Tg臆1.0 ng/ml 52.0 56.0 停药 [41] 2012 单中心随机研究 171 170 12 吸碘率=0,Tg < 2.0 ng/ml,TgAb < 100 IU/ml 41.5 68.8 停药 [37] 2012 多中心随机研究 214 207 6~9 吸碘率 < 0.1%,Tg < 2.0 ng/ml 85.0 88.9 停药或rhTSH [38] 2012 多中心随机研究 347 337 6~10 吸碘率=0,甲状腺超声正常,Tg臆1.0 ng/ml 91.2 93.4 停药或rhTSH 注:表中,Tg:甲状腺球蛋白;TgAb:甲状腺球蛋白抗体;rhTSH:重组人促甲状腺激素。 -
[1] 中华医学会内分泌学分会, 中华医学会外科学分会内分泌学组, 中国抗癌协会头颈肿瘤专业委员会, 等.甲状腺结节和分化型甲状腺癌诊治指南[J].中华内分泌代谢杂志, 2012, 28(10):779-797. doi: 10.3760/cma.j.issn.1000-6699.2012.10.002
[2] Molinaro E, Viola D, Passannanti P, et al. Recombinant human TSH(rhTSH) in 2009:new perspectives in diagnosis and therapy[J]. Q J Nucl Med Mol Imaging, 2009, 53(5):490-502. [3] Pacini F, Molinaro E, Castagna MG, et al. Ablation of thyroid residues with 30 mCi 131I:a comparison in thyroid cancer patients prepared with recombinant human TSH or thyroid hormone withdrawal[J]. J Clin Endocrinol Metab, 2002, 87(9):4063-4068. doi: 10.1210/jc.2001-011918 [4] Pacini F, Ladenson PW, Schlumberger M, et al. Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma:results of an international, randomized, controlled study[J]. J Clin Endocrinol Metab, 2006, 91(3):926-932. doi: 10.1210/jc.2005-1651 [5] Schlumberger M, Ricard M, De Pouvourville G, et al. How the availability of recombinant human TSH has changed the management of patients who have thyroid cancer[J]. Nat Clin Pract Endocrinol Metab, 2007, 3(9):641-650. doi: 10.1038/ncpendmet0594 [6] Hänscheid H, Lassmann M, Luster M, et al. Iodine biokinetics and dosimetry in radioiodine therapy of thyroid cancer:procedures and results of a prospective international controlled study of ablation after rhTSH or hormone withdrawal[J]. J Nucl Med, 2006, 47(4):648-654. [7] 关海霞, 陆汉魁.重组人促甲状腺激素在甲状腺疾病诊治中的应用[J].中华核医学与分子影像杂志, 2012, 32(4):311-314. doi: 10.3760/cma.j.issn.2095-2848.2012.04.023
[8] Tuttle RM, Brokhin M, Omry G, et al. Recombinant human TSH-assisted radioactive iodine remnant ablation achieves short-term clinical recurrence rates similar to those of traditional thyroid hormone withdrawal[J]. J Nucl Med, 2008, 49(5):764-770. [9] Zanotti-Fregonara P, Hindié E, Toubert ME, et al. What role for recombinant human TSH in the treatment of metastatic thyroid cancer?[J]. Eur J Nucl Med Mol Imaging, 2009, 36(6):883-885. doi: 10.1007/s00259-008-1046-0 [10] Luster M, Lippi F, Jarzab B, et al. rhTSH-aided radioiodine ablation and treatment of differentiated thyroid carcinoma:a comprehensive review[J]. Endocr Relat Cancer, 2005, 12(1):49-64. doi: 10.1677/erc.1.00830 [11] Rosário PW, Borges MA, Purisch S. Preparation with recombinant human thyroid-stimulating hormone for thyroid remnant ablation with 131I is associated with lowered radiotoxicity[J]. J Nucl Med, 2008, 49(11):1776-1782. doi: 10.2967/jnumed.108.050591 [12] Frigo A, Dardano A, Danese E, et al. Chromosome translocation frequency after radioiodine thyroid remnant ablation:a comparison between recombinant human thyrotropin stimulation and prolonged levothyroxine withdrawal[J]. J Clin Endocrinol Metab, 2009, 94(9):3472-3476. doi: 10.1210/jc.2008-2830 [13] Barbaro D, Boni G, Meucci G, et al. Radioiodine treatment with 30 mCi after recombinant human thyrotropin stimulation in thyroid cancer:effectiveness for postsurgical remnants ablation and possible role of iodine content in L-thyroxine in the outcome of ablation[J]. J Clin Endocrinol Metab, 2003, 88(9):4110-4115. doi: 10.1210/jc.2003-030298 [14] Rosario PW, Mineiro FA, Lacerda RX, et al. Long-term follow-up of at least five years after recombinant human thyrotropin compared to levothyroxine withdrawal for thyroid remnant ablation with radioactive iodine[J]. Thyroid, 2012, 22(3):332-333. doi: 10.1089/thy.2011.0242 [15] Barbaro D, Boni G, Meucci G, et al. Recombinant human thyroid-stimulating hormone is effective for radioiodine ablation of post-surgical thyroid remnants[J]. Nucl Med Commun, 2006, 27(8):627-632. doi: 10.1097/00006231-200608000-00005 [16] Taieb D, Sebag F, Cherenko M, et al. Quality of life changes and clinical outcomes in thyroid cancer patients undergoing radioiodine remnant ablation(RRA)with recombinant human TSH(rhTSH):a randomized controlled study[J]. Clin Endocrinol(Oxf), 2009, 71(1):115-123. doi: 10.1111/j.1365-2265.2008.03424.x [17] Molinaro E, Giani C, Agate L, et al. Patients with differentiated thyroid cancer who underwent radioiodine thyroid remnant ablation with low-activity 131I after either recombinant human TSH or thyroid hormone therapy withdrawal showed the same outcome after a 10-year follow-up[J]. J Clin Endocrinol Metab, 2013, 98(7):2693-2700. doi: 10.1210/jc.2012-4137 [18] Luster M, Clarke SE, Dietlein M, et al. Guidelines for radioiodine therapy of differentiated thyroid cancer[J]. Eur J Nucl Med Mol Imaging, 2008, 35(10):1941-1959. doi: 10.1007/s00259-008-0883-1 [19] American Thyroid Association(ATA)Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer[J]. Thyroid, 2009, 19(11):1167-1214. doi: 10.1089/thy.2009.0110 [20] 傅宏亮, 杜学亮, 顾振辉, 等.腺叶切除不完全分化型甲状腺癌131I疗效观察[J].上海交通大学学报:医学版, 2010, 30(3):268-270.
[21] Bal CS, Kumar A, Pant GS. Radioiodine lobar ablation as an alternative to completion thyroidectomy in patients with differentiated thyroid cancer[J]. Nucl Med Commun, 2003, 24(2):203-208. doi: 10.1097/00006231-200302000-00013 [22] Pacini F, Castagna MG, Brilli L, et al. Thyroid cancer:ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2012, 23 Suppl 7:S110-119. [23] Bal CS, Kumar A, Chandra P, et al. A prospective clinical trial to assess the efficacy of radioiodine ablation as an alternative to completion thyroidectomy in patients with differentiated thyroid cancer undergoing sub-total thyroidectomy[J]. Acta Oncol, 2006, 45(8):1067-1072. doi: 10.1080/02841860500418377 [24] Santra A, Bal S, Mahargan S, et al. Long-term outcome of lobar ablation versus completion thyroidectomy in differentiated thyroid cancer[J]. Nucl Med Commun, 2011, 32(1):52-58. doi: 10.1097/MNM.0b013e328340e74c [25] Randolph GW, Daniels GH. Radioactive iodine lobe ablation as an alternative to completion thyroidectomy for follicular carcinoma of the thyroid[J]. Thyroid, 2002, 12(11):989-996. doi: 10.1089/105072502320908321 [26] Giovanella L, Piccardo A, Paone G, et al. Thyroid lobe ablation with iodine-131 in patients with differentiated thyroid carcinoma:a randomized comparison between 1.1 and 3.7 GBq activities[J]. Nucl Med Commun, 2013, 34(8):767-770. doi: 10.1097/MNM.0b013e3283622f3d [27] Barbesino G, Goldfarb M, Parangi S, et al. Thyroid lobe ablation with radioactive iodine as an alternative to completion thyroidectomy after hemithyroidectomy in patients with follicular thyroid carcinoma:long-term follow-up[J]. Thyroid, 2012, 22(4):369-376. doi: 10.1089/thy.2011.0198 [28] National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: thyroid carcinoma[EB/OL]. [2013-06-06]. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. [29] Pacini F, Castagna MG, Brilli L, et al. Thyroid cancer:ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2010, 21(5):214-219. [30] 董峰, 周荫保.分化型甲状腺癌术后131I清甲效果的影响因素[J].国际放射医学核医学杂志, 2010, 34(1):27-31. doi: 10.3760/cma.j.issn.1673-4114.2010.01.007
[31] Cheng W, Ma C, Fu H, et al. Low-or hgh-dse rdioiodine rmnant alation for dfferentiated tyroid crcinoma:a meta-analysis[J]. J Clin Endocrinol Metab, 2013, 98(4):1353-1360. doi: 10.1210/jc.2012-3682 [32] Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer[J]. Am J Med, 1994, 97(5):418-428. doi: 10.1016/0002-9343(94)90321-2 [33] Creutzig H. High or low dose radioiodine ablation of thyroid remnants?[J]. Eur J Nucl Med, 1987, 12(10):500-502. doi: 10.1007/BF00620474 [34] Johansen K, Woodhouse NJ, Odugbesan O. Comparison of 1073 MBq and 3700 MBq iodine-131 in postoperative ablation of residual thyroid tissue in patients with differentiated thyroid cancer[J]. J Nucl Med, 1991, 32(2):252-254. [35] Bal C, Padhy AK, Jana S, et al. Prospective randomized clinical trial to evaluate the optimal dose of 131I for remnant ablation in patients with differentiated thyroid carcinoma[J]. Cancer, 1996, 77(12):2574-2580. doi: 10.1002/(SICI)1097-0142(19960615)77:12<2574::AID-CNCR22>3.0.CO;2-O [36] Bal CS, Kumar A, Pant GS. Radioiodine dose for remnant ablation in differentiated thyroid carcinoma:a randomized clinical trial in 509 patients[J]. J Clin Endocrinol Metab, 2004, 89(4):1666-1673. doi: 10.1210/jc.2003-031152 [37] Mallick U, Harmer C, Yap B, et al. Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer[J]. N Engl J Med, 2012, 366(18):1674-1685. doi: 10.1056/NEJMoa1109589 [38] Schlumberger M, Catargi B, Borget I, et al. Strategies of radioiodine ablation in patients with low-risk thyroid cancer[J]. N Engl J Med, 2012, 366(18):1663-1673. doi: 10.1056/NEJMoa1108586 [39] Maenpaa HO, Heikkonen J, Vaalavirta L, et al. Low vs. high radioiodine activity to ablate the thyroid after thyroidectomy for cancer: a randomized study[J/OL]. PLoS One, 2008, 3(4): 1885[2013-06-06]. http://www.ncbi.nlm.nih.gov/pubmed/18382668. [40] DoiSA, Woodhouse NJ, Thalib L, et al. Ablation of the thyroid remnant and I-131 dose in differentiated thyroid cancer:a meta-analysis revisited[J]. Clin Med Res, 2007, 5(2):87-90. doi: 10.3121/cmr.2007.763 [41] Fallahi B, Beiki D, Takavar A, et al. Low versus high radioiodine dose in postoperative ablation of residual thyroid tissue in patients with differentiated thyroid carcinoma:a large randomized clinical trial[J]. Nucl Med Commun, 2012, 33(3):275-282. doi: 10.1097/MNM.0b013e32834e306a