Protocol 规程

Sponsor Protocol N ${}^{\circ }$${}^{\circ }$^(@){ }^{\circ} : IGR 2012/1913
赞助方议定书 N ${}^{\circ }$${}^{\circ }$^(@){ }^{\circ} : IGR 2012/1913

Cancer thyroïdien différencié à faible risque : le traitement ablatif par iode 131 est-il utile?
低风险分化型甲状腺癌：碘 131 消融治疗有用吗？

Differentiated thyroid cancer: is there a need for radioiodine ablation in low risk patients?
分化型甲状腺癌：低风险患者是否需要进行放射性碘消融？

Version n ${}^{\circ }1.1$${}^{\circ }1.1$^(@)1.1{ }^{\circ} 1.1 - February, ${06}^{\text{th}},2013$${06}^{\text{th }},2013$06^("th "),201306^{\text {th }}, 2013
版本 n ${}^{\circ }1.1$${}^{\circ }1.1$^(@)1.1{ }^{\circ} 1.1 - 2 月， ${06}^{\text{th}},2013$${06}^{\text{th }},2013$06^("th "),201306^{\text {th }}, 2013

SIGNATURE PAGE 签名页

Investigator center: 调查员中心：

Department: 部门：

1. $$$$qquad\qquad certify that I have read the protocol named «ESTIMABL 2"
   $$$$qquad\qquad 证明我已阅读名为 "ESTIMABL 2 "的协议

Signature : 签名 ：

STUDY CONTACTS 研究联系人

SYNOPSIS - PROTOCOL ESTIMABL 2
简要说明 - 议定书第 2 条

B) IDENTIFICATION OF SPONSOR
b) 确定提案国

C) GENERAL INFORMATION ON STUDY
C)学习概况

INDICATION: 指示：

METHODOLOGY: 方法：

PRIMARY OBJECTIVE: 主要目标：

SECONDARY OBJECTIVES: 次要目标：

• Salivary and lachrymal toxicities
  唾液和泪液毒性
• Patient’s quality of life, anxiety and fear of recurrence
  患者的生活质量、焦虑和对复发的恐惧
• Rate of patients without event at 5 years following thyroidectomy
  甲状腺切除术后 5 年未发生事件的患者比例
• Rate of patients without event at 3 and 5 years after thyroidectomy, according to the initial lymph node status
  根据最初的淋巴结状态，甲状腺切除术后 3 年和 5 年无事件发生的患者比例
• Recurrence rate (histologically proven) at three years following thyroidectomy
  甲状腺切除术后三年的复发率（组织学证实
• Future of patients experiencing en event.
  经历 en 事件的病人的未来。
• Costs of treatment and follow-up
  治疗和后续费用
• Rate of patients without event at 3 and 5 years after thyroidectomy, according to tumoral molecular characterization
  根据肿瘤分子特征，甲状腺切除术后 3 年和 5 年未发生事件的患者比例

INCLUSION CRITERIA: 纳入标准：

1. Patients with differentiated thyroid cancer (papillary, follicular or with Hurthle cells) in the absence of aggressive histological subtypes (poorly differentiated, tall-clear-cylindric cell, diffuse sclerosing or with an anaplastic component)
   分化型甲状腺癌患者（乳头状、滤泡状或伴有 Hurthle 细胞），且不伴有侵袭性组织学亚型（分化不良、高大透明细胞、弥漫硬化或伴有无性细胞）。
2. Patients having undergone a total thyroidectomy with complete (R0) tumor resection, with or without lymph node neck dissection
   接受过甲状腺全切除术，肿瘤完全切除（R0），并进行或未进行颈部淋巴结清扫的患者
3. Surgery performed 2 to 4 months before inclusion
   纳入前 2 至 4 个月进行过手术
4. Patients with low risk of recurrence: pT1amN0 or pT1amNx with a sum of the size of the lesions above 1 cm and equal to or less than 2 cm , or pT1bN0 or pT1bNx (TNM 2010 classification). (Patients with less than 6 lymph nodes in the neck dissection will be classified as Nx)
   低复发风险患者：pT1amN0 或 pT1amNx，病灶大小之和大于 1 厘米且等于或小于 2 厘米，或 pT1bN0 或 pT1bNx（TNM 2010 分类）。(颈部清扫淋巴结少于 6 个的患者将被归类为 Nx）。
5. Post-operative neck ultrasound (performed 2 to 4 months after surgery) showing the absence of abnormalities in the lateral lymph node compartments, or if abnormalities, no lymph nodes with abnormal cytology and/or thyroglobulin concentration in the aspirate fluid $>10\mathrm{ng}/\mathrm{mL}$$>10\mathrm{ng}/\mathrm{mL}$> 10ng//mL>10 \mathrm{ng} / \mathrm{mL}
   术后颈部超声波检查（术后 2 至 4 个月）显示侧淋巴结区无异常，如果有异常，则淋巴结细胞学无异常和/或抽吸液中无甲状腺球蛋白浓度 $>10\mathrm{ng}/\mathrm{mL}$$>10\mathrm{ng}/\mathrm{mL}$> 10ng//mL>10 \mathrm{ng} / \mathrm{mL} 。
6. Age $\ge 18$$\ge 18$>= 18\geq 18 years 年龄 $\ge 18$$\ge 18$>= 18\geq 18 岁
7. Performance status of 0 or 1
   性能状态为 0 或 1
8. Patients who signed the informed consent
   签署知情同意书的患者
9. Patients who can be followed-up annually during 5 years in order to assess the objectives of the study
   可在 5 年内每年对患者进行随访，以评估研究的目标
10. Women of childbearing age should have a negative pregnancy test before any radioiodine administration
    育龄妇女在使用任何放射性碘之前应进行阴性妊娠试验
11. Both patients with or without thyroglobulin antibodies are eligible
    有或没有甲状腺球蛋白抗体的患者均符合条件

NON INCLUSION CRITERIA: 非纳入标准：

1. Patients having undergone less than a total thyroidectomy
   未完成甲状腺全切除术的患者
2. Patients with aggressive histotype (poorly differentiated, tall-clear-cylindric cell, diffuse sclerosing, or with an anaplastic component)
   侵袭性组织型患者（分化不良、高大透明细胞、弥漫性硬化或伴有无弹性成分）
3. Patients having undergone surgery less than 2 months or more than 4 months before inclusion
   入选前 2 个月以内或 4 个月以上接受过手术的患者
4. Patients with cancer classified as pT1a unifocal (in which ablation is not necessary), or pT1N1, pT2, pT3, pT4 or N1 (who have a higher risk of recurrence) (classification TNM 2010)
   癌症分类为 pT1a 单灶（无需消融）或 pT1N1、pT2、pT3、pT4 或 N1（复发风险较高）的患者（2010 年 TNM 分类）。
5. Patient with known distant metastasis
   已知有远处转移的患者
6. Abnormal post-operative neck ultrasound of the lateral lymph node compartments
   术后颈部侧淋巴结超声检查异常
7. Patients with another malignancy not in remission for at least 2 years (except for in situ cervix uterine cancer, basocellular skin cancer)
   患有其他恶性肿瘤且病情未缓解至少 2 年的患者（原位子宫颈癌和基底细胞皮肤癌除外）。
8. Patients with a recent history of drugs affecting thyroid function, including injection of radiocontrast agents during the last 8 weeks.
   近期服用过影响甲状腺功能药物的患者，包括在过去 8 周内注射过放射性造影剂的患者。
9. Patients previously treated with radioactive iodine or who previously underwent a whole body scan with radioactive iodine
   曾接受过放射性碘治疗或曾接受过放射性碘全身扫描的患者
10. Pregnant or breast feeding women
    孕妇或哺乳期妇女
11. Subject with any kind of disorder that may compromise his/her ability to give written informed consent and/or to comply with study procedures
    受试者患有任何可能影响其作出书面知情同意和/或遵守研究程序的能力的疾病

PRIMARY AND SECONDARY EVALUATION CRITERIA:
主要和次要评估标准：

Primary criterion: 主要标准：

• At initial treatment, for patients randomized in the ablation group, the presence on the whole body scan of focus of radioiodine uptake outside the thyroid bed needing further treatment.
  在初始治疗时，对于随机分入消融组的患者，如果全身扫描结果显示甲状腺床外有放射性碘摄取灶，则需要进一步治疗。
• During follow up, in both groups, by the administration of an activity of $1131\ge 1,1\mathrm{GBq}(30\mathrm{mCi})$$1131\ge 1,1\mathrm{GBq}(30\mathrm{mCi})$1131 >= 1,1GBq(30mCi)1131 \geq 1,1 \mathrm{GBq}(30 \mathrm{mCi}) or by surgery because of:
  在随访过程中，两组患者都服用了 $1131\ge 1,1\mathrm{GBq}(30\mathrm{mCi})$$1131\ge 1,1\mathrm{GBq}(30\mathrm{mCi})$1131 >= 1,1GBq(30mCi)1131 \geq 1,1 \mathrm{GBq}(30 \mathrm{mCi}) 活性物质，或因以下原因接受了手术治疗：
• abnormal lymph node on neck ultrasound with an abnormal cytology and/or a thyroglobulin ( Tg ) concentration in the aspirate fluid $>10\mathrm{ng}/\mathrm{mL}$$>10\mathrm{ng}/\mathrm{mL}$> 10ng//mL>10 \mathrm{ng} / \mathrm{mL}
  颈部超声检查发现淋巴结异常，且细胞学检查结果异常和/或抽吸液中甲状腺球蛋白（Tg）浓度 $>10\mathrm{ng}/\mathrm{mL}$$>10\mathrm{ng}/\mathrm{mL}$> 10ng//mL>10 \mathrm{ng} / \mathrm{mL} 。
• and/or abnormal mass in the thyroid bed with an abnormal cytology
  和/或甲状腺床有异常肿块且细胞学检查异常
• and/or surgical resection of thyroid cancer
  和/或甲状腺癌手术切除
• and/or an elevated Tg level in the absence of anti-Tg antibodies (TgAb) defined according to Figure 1
  和/或在没有抗 Tg 抗体（TgAb）的情况下 Tg 水平升高，定义见图 1
• and/or the appearance of anti-Tg antibodies $(\mathrm{Ab})$$(\mathrm{Ab})$(Ab)(\mathrm{Ab}) above the upper limit of the normal range for the kit used, persisting on 2 measurements performed with the same kit at an interval of time of at least 6 months
  和/或出现抗绒毛膜促性腺激素抗体 $(\mathrm{Ab})$$(\mathrm{Ab})$(Ab)(\mathrm{Ab}) ，超过所用试剂盒正常范围的上限，且在使用同一试剂盒进行的两次测量中持续出现，间隔时间至少 6 个月
• and/or the increase of TgAb of more than $50\mathrm{\%}$$50\mathrm{\%}$50%50 \% on 2 measurements performed with the same kit with an interval of time of at least 6 months.
  和/或使用同一试剂盒进行的 2 次测量中，TgAb 的增加超过 $50\mathrm{\%}$$50\mathrm{\%}$50%50 \% ，且间隔时间至少 6 个月。
  Figure1: Definition of elevated Tg level in the absence of Tg antibodies ( TgAb )
  图 1：无 Tg 抗体（TgAb）时 Tg 水平升高的定义
  

  

SECONDARY CRITERIA 次级标准

• Lachrymal and Salivary Glands Toxicities will be evaluated by a specific questionnaire at baseline, 3 months, one year, and 3 years
  泪腺和唾液腺毒性将在基线、3 个月、1 年和 3 年时通过特定问卷进行评估
• Impact on patients quality of life, anxiety and recurrence fear will respectively be evaluated with the SF-36, STAI, IES, fear or cancer recurrence questionnaires at inclusion, 3 months after inclusion, 1 and 3 years post-operatively
  将分别在入组、入组后 3 个月、术后 1 年和 3 年使用 SF-36、STAI、IES、恐惧或癌症复发问卷评估对患者生活质量、焦虑和复发恐惧的影响
• Rate of patients without event at 5 years following thyroidectomy
  甲状腺切除术后 5 年未发生事件的患者比例
• Rate of events three and five years after thyroidectomy, adjusted on the initial lymph node status
  甲状腺切除术后三年和五年的事件发生率，根据最初的淋巴结状态进行调整
• Recurrence rate (histologically proven) at three years following thyroidectomy, and then at 5 years.
  甲状腺切除术后三年和五年的复发率（经组织学证实）。
• Rate of cure after an event
  事件发生后的治愈率
• Cost of treatment and follow-up
  治疗和后续费用
• Rate of events three and five years after thyroidectomy, adjusted on tumoral molecular characterization
  根据肿瘤分子特征调整甲状腺切除术后三年和五年的事件发生率

D) DESCRIPTION OF STUDY TREATMENTS- EXPERIMENTAL PLAN
d) 研究处理说明--实验计划

• rhTSH stimulation rhTSH 刺激

• Administration of 1.1 GBq of I131
  施用 1.1 GBq 的 I131

• Follow-up consists in: 后续行动包括：
• 10 (+/- 2 months) after surgery: a neck ultrasound and a serum Tg measurement after rhTSH stimulation
  术后 10 个月（+/- 2 个月）：在 rhTSH 刺激后进行颈部超声检查和血清 Tg 测量
• 2 years (+/- 2 months) after surgery: a serum Tg measurement under LT4 treatment (Tg/LT4)
  术后 2 年（+/- 2 个月）：在 LT4 治疗下测量血清 Tg（Tg/LT4）
• 3 years (+/- 2 months) after surgery: a neck ultrasound and a serum Tg/LT4
  术后 3 年（+/- 2 个月）：颈部超声波和血清 Tg/LT4
• 4 years (+/- 2 months) after surgery: a serum Tg/LT4
  术后 4 年（+/- 2 个月）：血清 Tg/LT4
• 5 years (+/- 2 months) after surgery: a neck ultrasound and a serum Tg/LT4
  术后 5 年（+/- 2 个月）：颈部超声检查和血清 Tg/LT4

Patients randomized in the follow up group
随访组的随机患者

TREATMENT DURATION: 7 days
疗程： 7 天

E) SAMPLE SIZE DETERMINATION
e) 确定样本量

F) DURATION OF STUDY
f) 学习期限

SOMMAIRE / TABLE OF CONTENT
目录

I. INTRODUCTION AND RATIONALE OF THE STUDY
I.研究的导言和基本原理

II. STUDY OBECTIVE II.研究目标

II.1. Primary Objective II.1.主要目标

II.2. Secondary Objective
II.2.次要目标

• Salivary and lachrymal toxicities
  唾液和泪液毒性
• Patient’s quality of life, anxiety and recurrence fear
  患者的生活质量、焦虑和对复发的恐惧
• Rate of patients without event at 5 years following thyroidectomy
  甲状腺切除术后 5 年未发生事件的患者比例
• Rate of patients without events 3 and 5 years after thyroidectomy, according to the initial lymph node status (NO vs Nx)
  根据最初的淋巴结状态（NO vs Nx），甲状腺切除术后 3 年和 5 年未发生事件的患者比例
• Recurrence rate (histologically proven) at three years following thyroidectomy, and then at 5 years.
  甲状腺切除术后三年和五年的复发率（经组织学证实）。
• Future of patients experiencing an event within the 5 years of thyroidectomy
  甲状腺切除术后 5 年内发生事件的患者比例
• Costs of treatment and follow-up
  治疗和后续费用
• Rate of patients without events 3 and 5 years after thyroidectomy, according to tumoral molecular characterization
  根据肿瘤分子特征，甲状腺切除术后 3 年和 5 年未发生事件的患者比例

III. METHODOLOGY III.方法论

IV. SELECTION OF PATIENTS
IV.患者的选择

IV.1. Inclusion criteria
IV.1.纳入标准

1. Patients with differentiated thyroid cancer (papillary, follicular or with Hurthle cells) in the absence of aggressive histological subtypes (poorly differentiated, tall-clear-cylindric cell, diffuse sclerosing or with an anaplastic component)
   分化型甲状腺癌患者（乳头状、滤泡状或伴有 Hurthle 细胞），且不伴有侵袭性组织学亚型（分化不良、高大透明细胞、弥漫硬化或伴有无性细胞）。
2. Patients having undergone a total thyroidectomy with complete (R0) tumor resection, with or without lymph neck node dissection
   接受过甲状腺全切除术，肿瘤完全切除（R0），并进行或未进行颈部淋巴结清扫的患者
3. Total thyroidectomy performed 2 to 4 months before inclusion
   在纳入前 2 至 4 个月进行全甲状腺切除术
4. Patients with low risk of recurrence: $\mathrm{pT}1\mathrm{amN}0$$\mathrm{pT}1\mathrm{amN}0$pT1amN0\mathrm{pT1amN0} or $\mathrm{pT}1\mathrm{amNx}$$\mathrm{pT}1\mathrm{amNx}$pT1amNx\mathrm{pT1amNx} with a sum of the size of the lesions above 1 cm and equal to or less than 2 cm , or $\mathrm{pT}1\mathrm{bN}0$$\mathrm{pT}1\mathrm{bN}0$pT1bN0\mathrm{pT1bN0} or $\mathrm{pT}1\mathrm{bNx}$$\mathrm{pT}1\mathrm{bNx}$pT1bNx\mathrm{pT1bNx} (tumor size: 1-2cm) (TNM 2010 classification). (Patients with less than 6 lymph nodes in the neck dissection will be classified as Nx).
   复发风险低的患者： $\mathrm{pT}1\mathrm{amN}0$$\mathrm{pT}1\mathrm{amN}0$pT1amN0\mathrm{pT1amN0} 或 $\mathrm{pT}1\mathrm{amNx}$$\mathrm{pT}1\mathrm{amNx}$pT1amNx\mathrm{pT1amNx} ，病灶大小之和大于 1 厘米且等于或小于 2 厘米，或 $\mathrm{pT}1\mathrm{bN}0$$\mathrm{pT}1\mathrm{bN}0$pT1bN0\mathrm{pT1bN0} 或 $\mathrm{pT}1\mathrm{bNx}$$\mathrm{pT}1\mathrm{bNx}$pT1bNx\mathrm{pT1bNx} （肿瘤大小：1-2 厘米）（TNM 2010 分类）。(颈部清扫淋巴结少于 6 个的患者将被归类为 Nx）。
5. Post-operative neck ultrasound (performed 2 to 4 months after surgery) showing the absence of abnormalities in the lateral lymph node compartments, or if abnormalities, no lymph node with abnormal cytology and/or thyroglobulin in the aspirate fluid $>10\mathrm{ng}/\mathrm{mL}$$>10\mathrm{ng}/\mathrm{mL}$> 10ng//mL>10 \mathrm{ng} / \mathrm{mL}
   术后颈部超声波检查（术后 2 至 4 个月）显示侧淋巴结区无异常，如果有异常，则淋巴结抽吸液中无异常细胞学和/或甲状腺球蛋白 $>10\mathrm{ng}/\mathrm{mL}$$>10\mathrm{ng}/\mathrm{mL}$> 10ng//mL>10 \mathrm{ng} / \mathrm{mL} .
6. Age $\ge 18$$\ge 18$>= 18\geq 18 years 年龄 $\ge 18$$\ge 18$>= 18\geq 18 岁
7. Performance status of 0 or 1
   性能状态为 0 或 1
8. Patients who signed the informed consent
   签署知情同意书的患者
9. Patients who can be followed-up annually during 5 years in order to assess the objectives of the study
   可在 5 年内每年对患者进行随访，以评估研究的目标
10. Women of childbearing age should have a negative pregnancy test before any radioiodine administration
    育龄妇女在使用任何放射性碘之前应进行阴性妊娠试验
11. Both patients with or without thyroglobulin antibodies are eligible
    有或没有甲状腺球蛋白抗体的患者均符合条件

IV.2. Exclusion criteria
IV.2.排除标准

1. Patients having undergone less than a total thyroidectomy
   未完成甲状腺全切除术的患者
2. Patients with aggressive histotype (poorly differentiated, tall-clear or cylindric cell, diffuse sclerosing, or with an anaplastic component)
   侵袭性组织型患者（分化不良、高大透明细胞或圆柱形细胞、弥漫性硬化或伴有无弹性成分）
3. Patients having undergone surgery less than 2 months or more than 4 months before inclusion
   入选前 2 个月以内或 4 个月以上接受过手术的患者
4. Patients with cancer classified as pT1a unifocal (in which ablation is useless), or pT1N1, pT2, pT3, pT4 or N1 (who have a higher risk of recurrence) (classification TNM 2010)
   癌症分类为 pT1a 单灶（消融无用）或 pT1N1、pT2、pT3、pT4 或 N1（复发风险较高）的患者（2010 年 TNM 分类）。
5. Patient with known distant metastasis
   已知有远处转移的患者
6. Abnormal post-operative neck ultrasound of the lateral lymph node compartments
   术后颈部侧淋巴结超声检查异常
7. Patients with another malignancy (except for in situ cervix uterine cancer, basocellular skin cancer or breast cancer in remission for at least 2 years)
   患有其他恶性肿瘤的患者（原位子宫颈癌、基底细胞皮肤癌或缓解至少 2 年的乳腺癌除外）
8. Patients with a recent history of drugs affecting thyroid function, including iodine containing medications or injection of radio-contrast agents
   近期服用过影响甲状腺功能的药物（包括含碘药物或注射放射造影剂）的患者
9. Patients previously treated with radioactive iodine or who previously underwent a whole body scan with radioactive iodine
   曾接受过放射性碘治疗或曾接受过放射性碘全身扫描的患者
10. Pregnancy or breast feeding women
    孕妇或哺乳期妇女
11. Subjects with any disorder that may compromise his/her ability to give written informed consent and/or to comply with study procedures
    受试者患有任何可能影响其做出书面知情同意和/或遵守研究程序的能力的疾病

V. TREATMENTS V.治疗

V.1. Randomization V.1.随机化

V.1.1. Time of randomization
V.1.1.随机化时间

• Initial inclusion criteria,
  初步纳入标准、
• Written signed consent form,
  书面签署同意书、
• Post-operative neck ultrasound showing the absence of abnormality in the lateral lymph node compartments,
  术后颈部超声显示侧淋巴结区无异常、
• Quality of life questionnaires (SF-36, Spielberger trait anxiety inventory (STAI), IES, fear of cancer recurrence).
  生活质量问卷（SF-36、Spielberger 特质焦虑量表（STAI）、IES、癌症复发恐惧）。

v.1.2. Randomization modalities
v.1.2.随机化模式

V.2. Description of treatments
V.2.疗程说明

• Ablation group: radioiodine ablation with an activity of 1.1 GBq ( 30 mCi ) after stimulation by rhTSH, and then follow-up during 5 years,
  消融组：在接受 rhTSH 刺激后进行 1.1 GBq（30 mCi）放射性碘消融，然后进行为期 5 年的随访、
• Follow-up Group: post-operative follow-up during 5 years (without post-operative radioiodine ablation).
  随访组：术后随访 5 年（无术后放射性碘消融）。

V.2.1. Patients randomized in the ablation group
V.2.1.消融组随机患者

• rhTSH stimulation : Between 2 and 4 months after surgery and start of LT4 treatment, intramuscular injections of rhTSH $(0.9\mathrm{mg})$$(0.9\mathrm{mg})$(0.9mg)(0.9 \mathrm{mg}) are performed on two consecutive days on LT4 treatment.
  rhTSH 刺激：手术后 2 至 4 个月，LT4 治疗开始后，在 LT4 治疗期间连续两天肌肉注射 rhTSH $(0.9\mathrm{mg})$$(0.9\mathrm{mg})$(0.9mg)(0.9 \mathrm{mg}) 。
  Administration of 1.1 GBq of I131: I131 is given orally 24 hours after the second injection of rhTSH. A whole body scan (WBS) is performed 2 to 5 days after the administration of I131, and uptake in the neck is quantified according to a standardized procedure. Activity present in the thyroid bed will be quantified with the ROI method, according to the protocol established by the Department of Medical Physics at the IGR, previously used in the ESTIMABL study.
  注射 1.1 GBq 的 I131：在第二次注射 rhTSH 24 小时后口服 I131。注射 I131 2 至 5 天后进行全身扫描（WBS），按照标准化程序量化颈部的摄取量。甲状腺床的活性将根据 IGR 医学物理系制定的方案，采用 ROI 方法进行量化，该方案曾在 ESTIMABL 研究中使用过。
• Follow-up consists in: 后续行动包括：
• 10 (+/- 2) months after surgery: a neck ultrasound and a serum Tg measurement after rhTSH stimulation
  术后 10 (+/- 2) 个月：rhTSH 刺激后进行颈部超声检查和血清 Tg 测量
• 2 years (+/- 2 months) after surgery: a serum Tg measurement on LT4 treatment (Tg/LT4)
  术后 2 年（+/- 2 个月）：LT4 治疗期间的血清 Tg 测量（Tg/LT4）
• 3 years (+/- 2 months) after surgery: a neck ultrasound and a serum Tg/LT4
  术后 3 年（+/- 2 个月）：颈部超声波和血清 Tg/LT4
• 4 years (+/- 2 months) after surgery: a serum Tg/LT4
  术后 4 年（+/- 2 个月）：血清 Tg/LT4
• 5 years (+/- 2 months) after surgery: a neck ultrasound and a serum Tg/LT4
  术后 5 年（+/- 2 个月）：颈部超声检查和血清 Tg/LT4

V.2.2. Patients randomized in the follow up group
V.2.2.随访组的随机患者

In both groups, the aim of LT4 treatment is to maintain the serum TSH level between 0.3 and $1\mathrm{mU}/\mathrm{L}$$1\mathrm{mU}/\mathrm{L}$1mU//L1 \mathrm{mU} / \mathrm{L}.
在这两组中，LT4治疗的目的是将血清促甲状腺激素水平维持在0.3和 $1\mathrm{mU}/\mathrm{L}$$1\mathrm{mU}/\mathrm{L}$1mU//L1 \mathrm{mU} / \mathrm{L} 之间。

VI. EVALUATION CRITERIA VI.评估标准

VI.1. Primary criterion VI.1.首要标准

• At initial treatment, for patients randomized in the ablation group, the presence on the WBS of focus of radioiodine uptake outside the thyroid bed needing further treatment.
  在初始治疗时，对于随机抽取的消融组患者，如果在 WBS 上发现甲状腺床以外的放射性碘摄取灶，则需要进一步治疗。
• During follow up, for patients in both groups, administration of an activity of I131 $\ge 1.1\mathrm{GBq}$$\ge 1.1\mathrm{GBq}$>= 1.1GBq\geq 1.1 \mathrm{GBq} ( 30 mCi ) or surgery for:
  在随访期间，两组患者都要接受 I131 $\ge 1.1\mathrm{GBq}$$\ge 1.1\mathrm{GBq}$>= 1.1GBq\geq 1.1 \mathrm{GBq} (30 mCi) 或手术治疗：
• abnormal lymph node on neck ultrasound with an abnormal cytology and/or a thyroglobulin ( Tg ) level in the aspirate fluid $>10\mathrm{ng}/\mathrm{mL}$$>10\mathrm{ng}/\mathrm{mL}$> 10ng//mL>10 \mathrm{ng} / \mathrm{mL}
  颈部超声检查发现淋巴结异常，且细胞学检查结果异常和/或抽吸液中甲状腺球蛋白（Tg）水平 $>10\mathrm{ng}/\mathrm{mL}$$>10\mathrm{ng}/\mathrm{mL}$> 10ng//mL>10 \mathrm{ng} / \mathrm{mL} 。
• and/or an abnormal mass in the thyroid bed with an abnormal cytology
  和/或甲状腺床出现异常肿块且细胞学检查异常
• and/or an elevated Tg level in the absence of anti-Tg antibodies (TgAb) defined according to Figure 1
  和/或在没有抗 Tg 抗体（TgAb）的情况下 Tg 水平升高，定义见图 1
• and/or the appearance of anti-Tg antibodies (Ab) above the upper limit of the normal range for the kit used, persisting on 2 measurements performed with the same kit at an interval of time of at least 6 months
  和/或出现超过所用试剂盒正常范围上限的抗绒毛膜促性腺激素抗体 (Ab)，且在使用同一试剂盒进行的两次测量中持续出现，间隔时间至少 6 个月
• and/or the increase of TgAb by more than $50\mathrm{\%}$$50\mathrm{\%}$50%50 \% on 2 measurements performed with the same kit at an interval of time of at least 6 months.
  和/或在至少 6 个月的时间间隔内，使用同一试剂盒进行的 2 次测量中，TgAb 的增加超过 $50\mathrm{\%}$$50\mathrm{\%}$50%50 \% 。

Figure1: Definition of elevated Tg level in the absence of Tg antibodies ( TgAb )
图 1：无 Tg 抗体（TgAb）时 Tg 水平升高的定义

VI.1.1. Tg central measurement
VI.1.1.Tg 中心测量

VI.1.2. Neck ultrasound VI.1.2.颈部超声波

VI.1.3. Post ablation whole body scan
VI.1.3.消融后全身扫描

VI.2. Secondary criteria
VI.2 二级标准

VI.2.1. Salivary and Lachrymal toxicities
VI.2.1.唾液和泪液毒性

• At randomization (baseline)
  随机化时（基线）
• At the end of the hospitalization for radioiodine ablation
  放射性碘消融住院治疗结束时
• 10 (+/- 2) months after surgery
  术后 10 (+/- 2) 个月
• 3 years after surgery
  术后 3 年

• At randomization (baseline)
  随机化时（基线）
• At $3(+/-1)$$3(+/-1)$3(+//-1)3(+/-1) month after randomization with questionnaire given at the randomization, to fill in at home and send by the patient with a stamped envelop provided at randomization.
  随机抽样后 $3(+/-1)$$3(+/-1)$3(+//-1)3(+/-1) 个月，使用随机抽样时提供的问卷，由患者在家填写并用随机抽样时提供的贴有邮票的信封寄出。
• 10 (+/- 2) months after surgery
  术后 10 (+/- 2) 个月
• 3 years after surgery
  术后 3 年

VI.2.2. Impact on patient's quality of life, anxiety and recurrence fear
VI.2.2.对患者生活质量、焦虑和复发恐惧的影响

- The SF-36 scale
- SF-36 量表

• The Spielberger State-Trait Anxiety Inventory (STAI)
  斯皮尔伯格状态-特质焦虑量表（STAI）

• Impact of event scale-revised (IES-R)
  事件影响量表修订版 (IES-R)

• Fear of cancer recurrence inventory
  癌症复发恐惧清单

VI.2.3. Rate of events five years after thyroidectomy
VI.2.3.甲状腺切除术后五年的事件发生率

VI.2.4. Rate of events three and five years after thyroidectomy adjusted on the lymph node status
VI.2.4.根据淋巴结状态调整甲状腺切除术后三年和五年的事件发生率

VI.2.5. Recurrence rate (histologically proven) at three and five years after
VI.2.5.术后三年和五年的复发率（经组织学证实

VI.2.6. Management and follow-up cost
VI.2.6.管理和后续费用

VI.2.7. Rate of events three and five years after thyroidectomy adjusted on the tumoral molecular characterization
VI.2.7.根据肿瘤分子特征调整甲状腺切除术后三年和五年的事件发生率

VII. DETERMINATION OF SAMPLE SIZE AND STATISTICAL ANALYSIS
VII.样本量的确定和统计分析

VII.1. Determination of sample size
VII.1.样本量的确定

VII.1.1. Statistical analysis
VII.1.1.统计分析

Main criterion: 主要标准：

Secondary criteria: 次要标准：

• Incidence and grade of salivary and lachrymal toxicities will be compared between groups using a chi-2 test.
  各组之间唾液和泪液毒性的发生率和等级将通过 chi-2 检验进行比较。
  Quality of life, anxiety and recurrence fear: The investigator will inform the patient on the objective of QoL data collection. QoL data may be not exploitable in case of great number of missing questionnaires. Data will be analyzed according to the scoring manual of each questionnaire. A longitudinal analysis using a mixed model will be used to take into account of repeated QoL assessment and the initial value. If this analysis shows a significant different effect between groups or an interaction between treatment and time, an analysis of the treatment effect on quality of life will be carried out at each time. Mean sub-scale scores will be compared using a Student test for each time of evaluation (or a Kruskall-Wallis non parametric test if they are not normally distributed).
  生活质量、焦虑和复发恐惧：研究人员将告知患者收集 QoL 数据的目的。如果有大量问卷缺失，则可能无法利用 QoL 数据。数据将根据每份问卷的评分手册进行分析。将使用混合模型进行纵向分析，以考虑重复 QoL 评估和初始值。如果分析结果显示组间存在明显差异或治疗与时间之间存在交互作用，则将对每次治疗对生活质量的影响进行分析。在每次评估时，将使用学生检验（或 Kruskall-Wallis 非参数检验，如果它们不是正态分布的话）对平均子量表得分进行比较。
  Cost of treatment and follow-up will be compared between groups using a non-parametric test.
  将使用非参数检验对各组的治疗和随访成本进行比较。
• The comparison of the rate of patients without events is also planned to be performed adjusted on the initial lymph node status involvement
  此外，还计划根据最初淋巴结受累情况，对未发生事件的患者比例进行比较。
  The comparison of the rate of patients without histollogically proven recurrence at 3 and 5 years following total thyroidectomy is also planned
  还计划对甲状腺全切除术后 3 年和 5 年内未经组织学证实的复发率进行比较
  The comparison of the rate of patients without recurrence is also planned to be performed according to the tumoral molecular characterization
  还计划根据肿瘤分子特征对无复发患者的比例进行比较

VIII. SERIOUS ADVERSE EVENTS
VIII.严重不良事件

VIII.1. Definition VIII.1.定义

An Adverse Event (AE) is:
不良事件（AE）是指

• Results in death or
  导致死亡或
• Is life-threatening or 危及生命或
• Requires patient hospitalization or prolongation of existing hospitalization or
  需要病人住院治疗或延长现有住院治疗或
• Results in persistent or significant disability/incapacity; or
  导致持续或严重残疾/丧失工作能力；或
• Results in a congenital abnormality/birth defect or abortion or
  导致先天性畸形/出生缺陷或流产或
• Is medically significant
  具有医学意义

The following are not considered adverse events (SAE)
以下情况不属于不良事件 (SAE)

• A Pre-planned hospitalization for a condition which existed at the start of study drug and which did not worsen during the course of study drug treatment
  在开始服用研究药物时就已存在的疾病，且在研究药物治疗过程中没有恶化，而计划前住院治疗
• Social admission (e.g., subject has no place to sleep; hospice facilities)
  社会收容（例如，受试者没有地方睡觉；临终关怀设施）
• Administrative admission (e.g., for yearly physical exam)
  行政入院（如年度体检）
• Protocol-specified admission during a clinical trial (e.g., biopsy, study drugs administration…)
  在临床试验期间按协议规定入院（如活检、服用研究药物......）。
• Optional admission not associated with a precipitating clinical AE (e.g., for elective cosmetic surgery)
  与诱发临床 AE 无关的选择性入院（如选择性整容手术）
• hospitalization < 24 hours (observation/ short-stay units)
  住院 < 24 小时（观察/短期住院病房）

An Expected Serious Adverse Event
预期严重不良事件

An unexpected Serious Adverse Event
意外严重不良事件

VIII.2. Recording and Reporting / Action to be taken in the case of a SAE
VIII.2.记录和报告/发生 SAE 时应采取的行动

Unité Fonctionnelle de Pharmacovigilance
药物警戒职能部门

1. A clear description in medical terminology
   清晰的医学术语描述
2. Whether the event was expected or not
   事件是否在预料之中
3. Its duration (start and end dates)
   持续时间（开始和结束日期）
4. Action taken and the necessity for corrective treatment or not, withdrawal of study drug(s) or not, and so on
   采取的行动以及是否有必要进行纠正治疗、是否有必要停用研究药物等
5. Its intensity (grade 1-5), according to NCI-CTCAE version 4.0 (a copy of the CTC version 4.0 can be downloaded from the cancer therapy evaluation program (CTEP) home page: http://ctep.info.nih.gov).
   根据 NCI-CTCAE 4.0 版，其强度（1-5 级）（CTC 4.0 版副本可从癌症治疗评估计划（CTEP）主页下载：http://ctep.info.nih.gov）。
6. Its relationship to the study drug or treatment, the pathology treated, another pathology or another concomitant treatment, or to a constraint linked to the research (period without treatment, further tests required for the research, and so on).
   与研究药物或治疗、所治疗的病理、另一种病理或另一种并发症治疗的关系，或与研究相关的限制因素（未治疗期、研究所需的进一步检查等）的关系。
7. Documentation of all co-medications and/or therapies
   所有联合用药和/或治疗的记录
8. Documentation of all relevant medical histories and/or co-existing diseases
   所有相关病史和/或并存疾病的文件记录
9. The outcome (where applicable). For non fatal events, developments should be followed up till either recovery or recovery of a previous state of health or till the stabilization of possible aftereffects.
   结果（如适用）。对于非致命事件，应跟踪事态发展，直至恢复或恢复到以前的健康状况，或直至可能的后遗症稳定下来。
   The investigator must also attach to the serious adverse event report form, wherever possible:
   研究者还必须尽可能在严重不良事件报告表后附上：

• A copy of the summary of hospitalization or prolongation of hospitalization
  住院或延长住院治疗的摘要副本
• A copy of the post-mortem report (if applicable)
  验尸报告副本（如适用）
• A copy of all relevant laboratory examinations and the dates on which these examinations were carried out, including relevant negative results, as well as normal laboratory ranges.
  所有相关实验室检查和检查日期的副本，包括相关的阴性结果以及实验室正常范围。
• All other documents that he judges useful and relevant.
  他认为有用和相关的所有其他文件。

VIII.3. Follow-up VIII.3.后续行动

VIII.4. Information given to investigators, ethics committee and regulatory authorities
VIII.4.向调查人员、伦理委员会和监管机构提供的信息

IX. STUDY DISCONTINUATION
IX.研究中止

• Frequency and/or unexpected severity of the toxicity,
  毒性发生的频率和/或意外严重程度、
• Recruitment of patients too low,
  病人招募率太低、
• Poor quality of the data collected,
  收集的数据质量差、
• Request of the Data Monitoring Committee
  数据监测委员会的要求

X. ETHICAL AND REGULATORY ASPECTS
X.伦理与监管问题

X.1. Rules and regulations
X.1.规则和条例

• The Public Healthcare Law ( $n^{\circ }$$n^{\circ }$n^(@)n^{\circ} 2004-806) of August 9, 2004, a partial adaptation of the European Directive (2001/20/EC) on the conduct of clinical trials,
  2004 年 8 月 9 日颁布的《公共医疗保健法》（ $n^{\circ }$$n^{\circ }$n^(@)n^{\circ} 2004-806）部分修改了关于开展临床试验的欧洲指令（2001/20/EC）、
• The European Directive (2001/20/EC and 2005/28/EC)
  欧洲指令（2001/20/EC 和 2005/28/EC）
• The Informatics and Liberties Law ( $n^{\circ }78$$n^{\circ }78$n^(@)78n^{\circ} 78-17) of January 6, 1978 modified by Law $n^{\circ }$$n^{\circ }$n^(@)n^{\circ} 2004-801 of August 6, 2004 relative to the protection of physical persons with respect to the treatment of personal information.
  1978 年 1 月 6 日颁布的《信息学与自由法》（ $n^{\circ }78$$n^{\circ }78$n^(@)78n^{\circ} 78 -17）经 2004 年 8 月 6 日颁布的关于在处理个人信息时保护自然人的 $n^{\circ }$$n^{\circ }$n^(@)n^{\circ} 2004-801 号法律修订。
• Law $n^{\circ }$$n^{\circ }$n^(@)n^{\circ} 2002-303 of March 4, 2002 relative to patients’ rights and to the quality of the healthcare system,
  2002 年 3 月 4 日颁布的关于患者权利和医疗系统质量的第 $n^{\circ }$$n^{\circ }$n^(@)n^{\circ} 2002-303 号法律、
• Appendix 13 of the E. U. Guide to Good Manufacturing Practices (revised and adopted in July 2003 by the European Commission),
  《欧盟良好生产规范指南》附录 13（欧盟委员会于 2003 年 7 月修订并通过）、
• The Good Clinical Practices guidelines (International Conference on Harmonization ICH E6 and Statistical Principles for Clinical Trials (ICH E9).
  良好临床实践指南》（国际协调会议 ICH E6 和《临床试验统计原则》（ICH E9））。

X.2. Committee for the Protection of Persons (CPP) - Competent Authority
X.2.人员保护委员会（CPP）--主管机构

X.3. Information and Consent of Participants
X.3.参与者的信息和同意书

X.4. Principal Investigator Responsibilities
X.4.首席研究员的职责

• providing the Sponsor with his/her CV as well as the investigators’ ones,
  向赞助者提供自己和研究人员的简历、
  -identifying members of his/her team participating in the trial and defining their responsibilities, - recruiting patients after receiving the Sponsor’s approval,
  -确定其团队中参与试验的成员并明确他们的职责， - 在获得申办者批准后招募患者、

• personally obtaining the informed consent form which has been dated and signed by the participant in the research prior to any specific trial selection procedure,
  在进行任何特定试验选择程序之前，亲自获取研究参与者已注明日期并签名的知情同意书、
• regularly completing the case report form (CRF) for each patient included in the trial and ensuring that the Clinical Research Assistant (CRA) mandated by the Sponsor has direct access to source documents in order to validate information on the CRF,
  定期为每位参与试验的患者填写病例报告表 (CRF)，并确保申办方授权的临床研究助理 (CRA) 可直接查阅原始文件，以验证 CRF 上的信息、
• dating, correcting and signing the corrections on the CRF for each patient included in the trial, - accepting regular visits from a CRA and possibly visits from auditors mandated by the Sponsor or inspectors from the regulatory authorities.
  为每位参与试验的患者填写、更正和签署通用报告格式上的更正内容， - 接受注册审评员的定期访问，也可能接受申办方授权的审计员或监管机构检查员的访问。
  All documentation concerning the trial (protocol, consent form, case report form, investigator file, etc…), as well as the original documents (laboratory results, imaging studies, medical consultation reports, clinical examination reports, etc.) is considered confidential and should be kept in a safe place. The Principal Investigator should keep data as well as a list of patient-identifying data for at least 15 years after the end of the study.
  与试验有关的所有文件（方案、同意书、病例报告表、研究者档案等）以及原始文件（实验室结果、影像学研究、医疗咨询报告、临床检查报告等）均被视为机密文件，应妥善保管。研究结束后，主要研究人员应将数据以及患者身份识别数据清单至少保存 15 年。

XI. DATA COLLECTION XI.数据收集

XII. QUALITY ASSURANCE - MONITORING
XII.质量保证--监测

• trial management in accordance with the procedures at the Institut Gustave Roussy,
  按照古斯塔夫-鲁西研究所的程序进行试验管理、
• quality control of data at the investigating site by the Sponsor’s CRA,
  由申办者的 CRA 对调查地点的数据进行质量控制、
• possible auditing of investigating centre.
  可能对调查中心进行审计。

Monitoring 监测

XIII. DATA OWNERSHIP / PUBLICATION POLICY
XIII.数据所有权/出版政策

1. Leenhardt L, Grosclaude P 2011 [Epidemiology of thyroid carcinoma over the world]. Ann Endocrinol (Paris) 72:136-148
   Leenhardt L, Grosclaude P 2011 [全球甲状腺癌流行病学]。Ann Endocrinol (Paris) 72:136-148
2. Sassolas G, Hafdi-Nejjari Z, Remontet L, Bossard N, Belot A, Berger-Dutrieux N, DecaussinPetrucci M, Bournaud C, Peix JL, Orgiazzi J, Borson-Chazot F 2009 Thyroid cancer: is the incidence rise abating? Eur J Endocrinol 160:71-79
   Sassolas G、Hafdi-Nejjari Z、Remontet L、Bossard N、Belot A、Berger-Dutrieux N、Decaussin-Petrucci M、Bournaud C、Peix JL、Orgiazzi J、Borson-Chazot F 2009 甲状腺癌：发病率上升的趋势是否正在减弱？欧洲内分泌学杂志》160:71-79
3. Davies L, Welch HG 2006 Increasing incidence of thyroid cancer in the United States, 1973-2002. Jama 295:2164-2167
   Davies L, Welch HG 2006 美国甲状腺癌发病率不断上升，1973-2002 年。Jama 295:2164-2167
4. Leenhardt L, Grosclaude P, Cherie-Challine L 2004 Increased incidence of thyroid carcinoma in france: a true epidemic or thyroid nodule management effects? Report from the French Thyroid Cancer Committee. Thyroid 14:1056-1060
   Leenhardt L, Grosclaude P, Cherie-Challine L 2004 法国甲状腺癌发病率上升：是真正的流行病还是甲状腺结节管理效应？法国甲状腺癌委员会的报告。甲状腺 14:1056-1060
5. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM 2009 Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19:1167-1214
   Cooper DS、Doherty GM、Haugen BR、Kloos RT、Lee SL、Mandel SJ、Mazzaferri EL、McIver B、Pacini F、Schlumberger M、Sherman SI、Steward DL、Tuttle RM 2009 修订的美国甲状腺协会甲状腺结节和分化型甲状腺癌患者管理指南。甲状腺 19:1167-1214
6. Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JW, Wiersinga W 2006 European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 154:787-803
   Pacini F、Schlumberger M、Dralle H、Elisei R、Smit JW、Wiersinga W，2006 年欧洲就滤泡上皮分化型甲状腺癌患者的治疗达成共识。Eur J Endocrinol 154:787-803
7. Jonklaas J, Sarlis NJ, Litofsky D, Ain KB, Bigos ST, Brierley JD, Cooper DS, Haugen BR, Ladenson PW, Magner J, Robbins J, Ross DS, Skarulis M, Maxon HR, Sherman SI 2006 Outcomes of patients with differentiated thyroid carcinoma following initial therapy. Thyroid 16:12291242
   Jonklaas J、Sarlis NJ、Litofsky D、Ain KB、Bigos ST、Brierley JD、Cooper DS、Haugen BR、Ladenson PW、Magner J、Robbins J、Ross DS、Skarulis M、Maxon HR、Sherman SI 2006 分化型甲状腺癌患者的初始治疗效果。甲状腺 16:12291242
8. Jonklaas J, Cooper DS, Ain KB, Bigos T, Brierley JD, Haugen BR, Ladenson PW, Magner J, Ross DS, Skarulis MC, Steward DL, Maxon HR, Sherman SI 2010 Radioiodine therapy in patients with stage I differentiated thyroid cancer. Thyroid 20:1423-1424
   Jonklaas J、Cooper DS、Ain KB、Bigos T、Brierley JD、Haugen BR、Ladenson PW、Magner J、Ross DS、Skarulis MC、Steward DL、Maxon HR、Sherman SI 2010 分化期甲状腺癌患者的放射性碘治疗。甲状腺 20:1423-1424
9. Hay ID, Thompson GB, Grant CS, Bergstralh EJ, Dvorak CE, Gorman CA, Maurer MS, Mclver B, Mullan BP, Oberg AL, Powell CC, van Heerden JA, Goellner JR 2002 Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients. World J Surg 26:879-885
   Hay ID、Thompson GB、Grant CS、Bergstralh EJ、Dvorak CE、Gorman CA、Maurer MS、Mclver B、Mullan BP、Oberg AL、Powell CC、van Heerden JA、Goellner JR 2002 六十年间（1940-1999 年）梅奥诊所治疗的甲状腺乳头状癌：2444 例连续治疗患者的初始治疗和长期疗效的时间趋势。世界外科杂志 26:879-885
10. Sawka AM, Thephamongkhol K, Brouwers M, Thabane L, Browman G, Gerstein HC 2004 Clinical review 170: A systematic review and metaanalysis of the effectiveness of radioactive iodine remnant ablation for well-differentiated thyroid cancer. J Clin Endocrinol Metab 89:3668-3676
    Sawka AM, Thephamongkhol K, Brouwers M, Thabane L, Browman G, Gerstein HC 2004 Clinical Review 170：放射性碘残留消融治疗分化良好的甲状腺癌的有效性的系统回顾和荟萃分析。J Clin Endocrinol Metab 89:3668-3676
11. Schlumberger M, Catargi B, Borget I, Deandreis D, Zerdoud S, Bridji B, Bardet S, Leenhardt L, Bastie D, Schvartz C, Vera P, Morel O, Benisvy D, Bournaud C, Bonichon F, Dejax C, Toubert ME, Leboulleux S, Ricard M, Benhamou E 2012 Strategies of radioiodine ablation in patients with low-risk thyroid cancer. N Engl J Med 366:1663-1673
    Schlumberger M、Catargi B、Borget I、Deandreis D、Zerdoud S、Bridji B、Bardet S、Leenhardt L、Bastie D、Schvartz C、Vera P、Morel O、Benisvy D、Bournaud C、Bonichon F、Dejax C、Toubert ME、Leboulleux S、Ricard M、Benhamou E 2012 年低危甲状腺癌患者的放射性碘消融策略。N Engl J Med 366:1663-1673
12. Mallick U, Harmer C, Yap B, Wadsley J, Clarke S, Moss L, Nicol A, Clark PM, Farnell K, McCready R, Smellie J, Franklyn JA, John R, Nutting CM, Newbold K, Lemon C, Gerrard G, Abdel-Hamid A, Hardman J, Macias E, Roques T, Whitaker S, Vijayan R, Alvarez P, Beare S, Forsyth S, Kadalayil L, Hackshaw A 2012 Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. N Engl J Med 366:1674-1685
    Mallick U、Harmer C、Yap B、Wadsley J、Clarke S、Moss L、Nicol A、Clark PM、Farnell K、McCready R、Smellie J、Franklyn JA、John R、Nutting CM、Newbold K、Lemon C、Gerrard G、Abdel-Hamid A、Hardman J、Macias E、Roques T、Whitaker S、Vijayan R、Alvarez P、Beare S、Forsyth S、Kadalayil L、Hackshaw A 2012 用低剂量放射性碘和甲状腺素α消融甲状腺癌。英国医学杂志》366：1674-1685
13. Pacini F, Ladenson PW, Schlumberger M, Driedger A, Luster M, Kloos RT, Sherman S, Haugen B, Corone C, Molinaro E, Elisei R, Ceccarelli C, Pinchera A, WahI RL, Leboulleux S, Ricard M, Yoo J, Busaidy NL, Delpassand E, Hanscheid H, Felbinger R, Lassmann M, Reiners C 2006 Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study. J Clin Endocrinol Metab 91:926-932
    Pacini F, Ladenson PW, Schlumberger M, Driedger A, Luster M, Kloos RT, Sherman S, Haugen B, Corone C, Molinaro E, Elisei R, Ceccarelli C, Pinchera A, WahI RL, Leboulleux S, Ricard M, Yoo J, Busaidy NL、Delpassand E、Hanscheid H、Felbinger R、Lassmann M、Reiners C 2006 分化型甲状腺癌患者使用重组人促甲状腺激素制备后甲状腺残余物的放射性碘消融：一项国际随机对照研究的结果。J Clin Endocrinol Metab 91:926-932
14. Hanscheid H, Lassmann M, Luster M, Thomas SR, Pacini F, Ceccarelli C, Ladenson PW, Wahl RL, Schlumberger M, Ricard M, Driedger A, Kloos RT, Sherman SI, Haugen BR, Carriere V, Corone C, Reiners C 2006 lodine 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 Nucl Med 47:648-654
    Hanscheid H、Lassmann M、Luster M、Thomas SR、Pacini F、Ceccarelli C、Ladenson PW、Wahl RL、Schlumberger M、Ricard M、Driedger A、Kloos RT、Sherman SI、Haugen BR、Carriere V、Corone C、Reiners C。J Nucl Med 47:648-654
15. Remy H, Borget I, Leboulleux S, Guilabert N, Lavielle F, Garsi J, Bournaud C, Gupta S, Schlumberger M, Ricard M 2008 131I effective half-life and dosimetry in thyroid cancer patients. J Nucl Med 49:1445-1450
    Remy H, Borget I, Leboulleux S, Guilabert N, Lavielle F, Garsi J, Bournaud C, Gupta S, Schlumberger M, Ricard M 2008 甲状腺癌患者的 131I 有效半衰期和剂量测定。核医学杂志 49:1445-1450
16. Schroeder PR, Haugen BR, Pacini F, Reiners C, Schlumberger M, Sherman SI, Cooper DS, Schuff KG, Braverman LE, Skarulis MC, Davies TF, Mazzaferri EL, Daniels GH, Ross DS, Luster M, Samuels MH, Weintraub BD, Ridgway EC, Ladenson PW 2006 A Comparison of Short-term Changes in Health-related Quality of Life in Thyroid Carcinoma Patients Undergoing Diagnostic Evaluation with rhTSH Compared to Thyroid Hormone Withdrawal. J Clin Endocrinol Metab 91:878-884
    Schroeder PR、Haugen BR、Pacini F、Reiners C、Schlumberger M、Sherman SI、Cooper DS、Schuff KG、Braverman LE、Skarulis MC、Davies TF、Mazzaferri EL、Daniels GH、Ross DS、Luster M、Samuels MH、Weintraub BD、Ridgway EC、Ladenson PW 2006 使用 rhTSH 进行诊断评估的甲状腺癌患者健康相关生活质量的短期变化与停用甲状腺激素的比较。J Clin Endocrinol Metab 91:878-884
17. Borget I, Corone C, Nocaudie M, Allyn M, lacobelli S, Schlumberger M, De Pouvourville G 2007 Sick leave for follow-up control in thyroid cancer patients: comparison between stimulation with Thyrogen and thyroid hormone withdrawal. Eur J Endocrinol 156:531-538
    Borget I、Corone C、Nocaudie M、Allyn M、lacobelli S、Schlumberger M、De Pouvourville G，2007 年 甲状腺癌患者请病假进行随访控制：使用促甲状腺激素刺激与停用甲状腺激素之间的比较。Eur J Endocrinol 156:531-538
18. Borget I, Remy H, Chevalier J, Ricard M, Allyn M, Schlumberger M, De Pouvourville G 2008 Length and cost of hospital stay of radioiodine ablation in thyroid cancer patients: comparison between preparation with thyroid hormone withdrawal and thyrogen. Eur J Nucl Med Mol Imaging 35:1457-1463
    Borget I, Remy H, Chevalier J, Ricard M, Allyn M, Schlumberger M, De Pouvourville G 2008 甲状腺癌患者放射性碘消融的住院时间和费用：停用甲状腺激素和甲状腺素准备之间的比较。Eur J Nucl Med Mol Imaging 35:1457-1463
19. Mandel SJ, Mandel L 2003 Radioactive iodine and the salivary glands. Thyroid 13:265-271
    Mandel SJ, Mandel L 2003 放射性碘与唾液腺。甲状腺 13:265-271
20. Kloos RT, Duvuuri V, Jhiang SM, Cahill KV, Foster JA, Burns JA 2002 Nasolacrimal drainage system obstruction from radioactive iodine therapy for thyroid carcinoma. J Clin Endocrinol Metab 87:5817-5820
    Kloos RT, Duvuuri V, Jhiang SM, Cahill KV, Foster JA, Burns JA 2002 甲状腺癌放射性碘治疗引起的鼻泪管引流系统阻塞。J Clin Endocrinol Metab 87:5817-5820
21. Rosario PW, Xavier AC, Calsolari MR 2011 Value of Postoperative Thyroglobulin and Ultrasonography for the Indication of Ablation and (131)। Activity in Patients with Thyroid Cancer and Low Risk of Recurrence. Thyroid 21:46-53
    Rosario PW, Xavier AC, Calsolari MR 2011 甲状腺癌低复发风险患者术后甲状腺球蛋白和超声波检查对消融指征和 (131)। 活性的价值。甲状腺 21:46-53
22. Vaisman A, Orlov S, Yip J, Hu C, Lim T, Dowar M, Freeman JL, Walfish PG 2010 Application of post-surgical stimulated thyroglobulin for radioiodine remnant ablation selection in low-risk papillary thyroid carcinoma. Head Neck 32:689-698
    Vaisman A, Orlov S, Yip J, Hu C, Lim T, Dowar M, Freeman JL, Walfish PG 2010 应用手术后刺激甲状腺球蛋白对低风险甲状腺乳头状癌进行放射性碘残留消融选择。头颈部 32:689-698
23. Tala Jury HP, Castagna MG, Fioravanti C, Cipri C, Brianzoni E, Pacini F 2010 Lack of association between urinary iodine excretion and successful thyroid ablation in thyroid cancer patients. J Clin Endocrinol Metab 95:230-237
    Tala Jury HP、Castagna MG、Fioravanti C、Cipri C、Brianzoni E、Pacini F 2010 甲状腺癌患者尿碘排泄量与甲状腺消融成功之间缺乏关联。J Clin Endocrinol Metab 95:230-237
24. Nascimento C, Borget I, Al Ghuzlan A, Deandreis D, Chami L, Travagli JP, HartI D, Lumbroso J, Chougnet C, Lacroix L, Baudin E, Schlumberger M, Leboulleux S 2011 Persistent disease and recurrence in differentiated thyroid cancer patients with undetectable postoperative stimulated thyroglobulin level. Endocr Relat Cancer 18:R29-40
    Nascimento C, Borget I, Al Ghuzlan A, Deandreis D, Chami L, Travagli JP, HartI D, Lumbroso J, Chougnet C, Lacroix L, Baudin E, Schlumberger M, Leboulleux S 2011 在术后检测不到刺激甲状腺球蛋白水平的分化型甲状腺癌患者中，疾病的持续存在和复发。内分泌相关癌症 18:R29-40
25. Schlumberger M, Borget I, Nascimento C, Brassard M, Leboulleux S 2011 Treatment and followup of low-risk patients with thyroid cancer. Nature reviews 7:625-628
    Schlumberger M, Borget I, Nascimento C, Brassard M, Leboulleux S 2011 低风险甲状腺癌患者的治疗和随访。自然评论 7:625-628
26. Kim TH, Park YJ, Lim JA, Ahn HY, Lee EK, Lee YJ, Kim KW, Hahn SK, Youn YK, Kim KH, Cho BY, Park do J 2012 The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer 118:1764-1773
    Kim TH、Park YJ、Lim JA、Ahn HY、Lee EK、Lee YJ、Kim KW、Hahn SK、Youn YK、Kim KH、Cho BY、Park do J 2012 BRAF（V600E）突变与甲状腺乳头状癌预后因素和不良临床结局的关系：一项荟萃分析。癌症 118:1764-1773
27. Schlumberger M, Hitzel A, Toubert ME, Corone C, Troalen F, Schlageter MH, Claustrat F, Koscielny S, Taieb D, Toubeau M, Bonichon F, Borson-Chazot F, Leenhardt L, Schvartz C, Dejax C, Brenot-Rossi I, Torlontano M, Tenenbaum F, Bardet S, Bussiere F, Girard JJ, Morel O, Schneegans O, Schlienger JL, Prost A, So D, Archambeaud F, Ricard M, Benhamou E 2007 Comparison of seven serum thyroglobulin assays in the follow-up of papillary and follicular thyroid cancer patients. J Clin Endocrinol Metab 92:2487-2495
    Schlumberger M、Hitzel A、Toubert ME、Corone C、Troalen F、Schlageter MH、Claustrat F、Koscielny S、Taieb D、Toubeau M、Bonichon F、Borson-Chazot F、Leenhardt L、Schvartz C、Dejax C、Brenot-Rossi I、Torlontano M、Tenenbaum F、Bardet S、Bussiere F、Girard JJ、Morel O、Schneegans O、Schlienger JL、Prost A、So D、Archambeaud F、Ricard M、Benhamou E 2007 在随访乳头状和滤泡状甲状腺癌患者时比较七种血清甲状腺球蛋白测定法。J Clin Endocrinol Metab 92:2487-2495
28. Brassard M, Borget I, Edet-Sanson A, Giraudet AL, Mundler O, Toubeau M, Bonichon F, BorsonChazot F, Leenhardt L, Schvartz C, Dejax C, Brenot-Rossi I, Toubert ME, Torlontano M, Benhamou E, Schlumberger M 2011 Long-Term Follow-Up of Patients with Papillary and Follicular Thyroid Cancer: A Prospective Study on 715 Patients. J Clin Endocrinol Metab
    Brassard M, Borget I, Edet-Sanson A, Giraudet AL, Mundler O, Toubeau M, Bonichon F, BorsonChazot F, Leenhardt L, Schvartz C, Dejax C, Brenot-Rossi I, Toubert ME, Torlontano M, Benhamou E, Schlumberger M 2011 年甲状腺乳头状癌和滤泡状癌患者的长期随访：715 例患者的前瞻性研究。临床内分泌代谢杂志
29. Roach M, 3rd, Hanks G, Thames H, Jr., Schellhammer P, Shipley WU, Sokol GH, Sandler H 2006 Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 65:965-974
    Roach M, 3rd, Hanks G, Thames H, Jr., Schellhammer P, Shipley WU, Sokol GH, Sandler H 2006 临床局部前列腺癌男性患者接受或不接受激素放疗后生化治疗失败的定义：RTOG-ASTRO 凤凰城共识会议的建议。Int J Radiat Oncol Biol Phys 65:965-974
30. Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D’Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen C, Thrasher JB, Thompson I 2007 Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes. The Journal of urology 177:540-545
    Cookson MS、Aus G、Burnett AL、Canby-Hagino ED、D'Amico AV、Dmochowski RR、Eton DT、Forman JD、Goldenberg SL、Hernandez J、Higano CS、Kraus SR、Moul JW、Tangen C、Thrasher JB、Thompson I：美国泌尿外科协会前列腺指南局部前列腺癌更新小组报告及手术结果报告标准建议》（American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes）。泌尿学杂志》177：540-545
31. Bruchon-Schweitzer ML, Paulhan I 1993 Manuel pour I’Inventaire d’AnxiéteTrait- Etat (Forme Y). Paris: ECPA;
    Bruchon-Schweitzer ML, Paulhan I 1993 Manuel pour I'Inventaire d'AnxiéteTrait- Etat (Forme Y)。巴黎：ECPA；
32. Horowitz M, Wilner N, Alvarez W 1979 Impact of Event Scale: a measure of subjective stress. Psychosomatic medicine 41:209-218
    Horowitz M，Wilner N，Alvarez W，1979 年 《事件影响量表：主观压力的测量方法》。心身医学 41:209-218
33. Sundin EC, Horowitz MJ 2002 Impact of Event Scale: psychometric properties. Br J Psychiatry 180:205-209
    Sundin EC, Horowitz MJ 2002 事件影响量表：心理测量特性。Br J Psychiatry 180:205-209
34. Brunet A, St-Hilaire A, Jehel L, King S 2003 Validation of a French version of the impact of event scale-revised. Canadian journal of psychiatry 48:56-61
    Brunet A、St-Hilaire A、Jehel L、King S，2003 年 法文版事件影响量表修订版的验证。加拿大精神病学杂志 48:56-61
35. Simard S, Savard J 2009 Fear of Cancer Recurrence Inventory: development and initial validation of a multidimensional measure of fear of cancer recurrence. Support Care Cancer 17:241-251
    Simard S, Savard J 2009 癌症复发恐惧量表：癌症复发恐惧多维度测量方法的开发与初步验证。癌症支持护理 17:241-251

ANNEXE 1: QUESTIONNAIRE DE TOXICITE SALIVAIRE ET LACRYMALE
附录 1：唾液和泪液毒性调查表

ANNEXE 2: QUESTIONNAIRE SUR LA SANTE : SF-36 POUR SITUATION AIGUE
附录 2：急性期健康问卷：SF-36

Date |__|_|____|__|_| Identification:

1. Dans l'ensemble, pensez-vous que votre santé est : entourez la réponse de votre choix
1.总体而言，您是否认为自己的健康状况是： 请圈选您所选择的答案