Recombinant TSH Stimulated Remnant Ablation Therapy in Thyroid Cancer: The Success Rate Depends on the Definition of Ablation Success—An Observational Study

Introduction
Patients with differentiated thyroid cancer (DTC) are treated with (near)-total thyroidectomy followed by remnant ablation. Optimal radioiodine-131 (131I) uptake is achieved by withholding thyroid hormone (THW), pretreatment with recombinant human Thyrotropin Stimulating Hormone (rhTSH) is an alternative. Six randomized trials have been published comparing THW and rhTSH, however comparison is difficult because an uniform definition of ablation success is lacking. Using a strict definition, we performed an observational study aiming to determine the efficacy of rhTSH as preparation for remnant ablation.
Patients and Methods
Adult DTC patients with, tumor stage T1b to T3, Nx, N0 and N1, M0 were included in a prospective multicenter observational study with a fully sequential design, using a stopping rule. All patients received remnant ablation with 131I using rhTSH. Ablation success was defined as no visible uptake in the original thyroid bed on a rhTSH stimulated 150 MBq 131I whole body scan (WBS) 9 months after remnant ablation, or no visible uptake in the original thyroid bed on a post therapeutic WBS when a second high dose was necessary.
Results
After interim analysis of the first 8 patients, the failure rate was estimated to be 69% (90% confidence interval (CI) 20-86%) and the inclusion of new patients had to be stopped. Final analysis resulted in an ablation success in 11 out of 17 patients (65%, 95% CI 38-86%).
Conclusion
According to this study, the efficacy of rhTSH in the preparation of 131I ablation therapy is inferior, when using a strict definition of ablation success. The current lack of agreement as to the definition of successful remnant ablation, makes comparison between different ablation strategies difficult. Our results point to the need for an international consensus on the definition of ablation success, not only in routine patient’s care but also for scientific reasons.
Trial Registration
Dutch Trial Registration NTR2395

引言
分化型甲状腺癌（differentiated thyroid cancer, DTC）患者的标准治疗方案为（近）全甲状腺切除术，随后实施残余灶消融。实现最优碘-131（radioiodine-131, 131I）摄取可通过甲状腺激素撤除（thyroid hormone withholding, THW）达成，而重组人促甲状腺激素（recombinant human Thyrotropin Stimulating Hormone, rhTSH）预处理是替代方案。目前已有六项随机对照试验对比了THW与rhTSH方案，但由于缺乏统一的消融成功定义，两类方案的疗效比较存在较大困难。本研究采用严格的消融成功定义，开展一项观察性研究，旨在明确rhTSH作为残余灶消融预处理方案的临床疗效。

患者与方法
本研究为前瞻性多中心观察性研究，采用完全序贯设计并设置中止规则，纳入的成人DTC患者肿瘤分期为T1b至T3期，淋巴结状态为Nx、N0或N1，无远处转移（M0）。所有患者均接受rhTSH预处理后行131I残余灶消融。消融成功的定义为：残余灶消融后9个月时，经rhTSH刺激后的150 MBq 131I全身扫描（whole body scan, WBS）未显示原甲状腺床存在放射性摄取；或当需再次给予高剂量131I时，治疗后全身扫描未显示原甲状腺床存在放射性摄取。

结果
对首批8例患者进行中期分析后，估算治疗失败率为69%（90%置信区间（confidence interval, CI）20%~86%），研究因此停止纳入新患者。最终共纳入17例患者，其中11例达到消融成功标准（65%，95% CI 38%~86%）。

结论
本研究结果显示，若采用严格的消融成功定义，rhTSH作为131I消融治疗预处理方案的疗效欠佳。当前临床对于残余灶消融成功的定义尚未达成共识，这使得不同消融策略之间的疗效比较存在难度。本研究结果提示，无论从临床常规诊疗还是科学研究的角度，均亟需制定一项关于消融成功定义的国际共识。

试验注册
荷兰试验注册编号：NTR2395