Abstract: Background　Differentiated thyroid cancer（DTC）patients need long-term follow-up services due to post-treatment persistence and high risks of recurrence.So it is essential to explore effective parameters for estimating the outcome and frequency of follow-up for these patients.Preablation stimulated thyroglobulin（ps-Tg）is an important prognostic parameter for DTC.However，its prognostic value in DTC（especially locally advanced DTC）patients has not been reported in China.Objective　To evaluate the value of ps-Tg，stimulated thyroglobulin（s-Tg）and thyroglobulin reduction index（TRI）in predicting long-term remission status in DTC（including locally advanced DTC）patients treated with thyroid remnant ablation with 131I，to identify the responses of the patients to treatment，and based on this，to deliver personalized management，or to alleviate the frequency of follow-ups in those with good responses to decrease psychological and economic burdens caused by frequent follow-ups.Methods　 From the long-term follow-up database of 992 DTC patients developed by Department of Breast & Thyroid Surgery，Suining Central Hospital，An Affiliated Hospital of Chongqing Medical University，those receiving thyroid remnant ablation with 131I between January 2004 and January 2012 were selected between October 2018 and January 2019.General characteristics（including gender，age，diameter of DTC，T/N/M staging，DTC invasion，lymph node capsule rupture，ps-Tg，s-Tg and TRI）and prognosis of the patients were collected.Multivariate Cox regression analysis was used to analyze the prognostic factors of patients with DTC.ROC curve analysis was carried out to explore the value of ps-Tg，s-Tg and TRI in predicting the long-term remission status in patients with DTC，and locally advanced DTC（T3-T4/Nx-N1 staging）.Log-rank test was performed to compare the survival status between groups.Results　 N staging，ps-Tg，s-Tg and TRI were associated with the prognosis of DTC patients in multivariate Cox regression analysis（P<0.05）.T staging，N staging，distribution of ps-Tg，s-Tg and TRI were also associated with the prognosis in multivariate Cox regression analysis（P<0.05）.ROC analysis identified ps-Tg of 10.0 μg/L（AUC=0.831），s-Tg of 1.0 μg/L（AUC=0.846）and TRI of 60%（AUC=0.722）as sensitive predictors for long-term remission in DTC patients.The sensitivity of ps-Tg，s-Tg and TRI was 74.1%，76.9% and 77.7%，respectively，while the specificity was 73.4%，74.7% and 72.8%，respectively.In the sub-population with locally advanced DTC，ps-Tg of 10.0 μg/L（AUC=0.864），s-Tg of 1.0 μg/L（AUC=0.859）and TRI of 62.5%（AUC=0.764）were effective indicators for predicting long-term remission with the sensitivity of 96.1%，54.2% and 74.0%，respectively.The specificity of ps-Tg，s-Tg and TRI was 55.4%，97.3% and 63.8%，respectively.The rate of long-term remission was significantly reduced when ps-Tg≥10.0 μg/L and s-Tg≥1.0 μg/L（P<0.05）.The cutoffs were also applicable to locally advanced DTC.DTC patients with TRI>60.0% achieved higher rate of long-term remission than that of those with TRI≤60.0%（P<0.05），while in locally advanced tumors this cutoff became 62.5%（P<0.05）.Conclusion　This study identified ps-Tg<10.0 μg/L，sTg<1.0 μg/L，and TRI>60.0% as highly sensitive predictors for excellent response in patients with DTC.And ps-Tg<10.0 μg/L，sTg<1.0 μg/L，and TRI>62.5% may be used for those with locally advanced DTC（T3-T4/ Nx-N1 staging）.

Key words: Thyroid neoplasms, Differentiated thyroid cancer, Thyroglobulin, Preablation stimulated thyroglobulin, Stimulated thyroglobulin, Thyroglobulin reduction index, Iodine, Forecasting, Long-term remission status

摘要： 背景　分化型甲状腺癌（DTC）因经治疗后疾病持续存在以及复发的风险较高而需长期随访，故探索有效的预测指标对患者预后评估及随访频次的判断具有重要意义。治疗前刺激性甲状腺球蛋白（ps-Tg）对DTC患者预后的评估具有重要价值，但其在DTC尤其是局部晚期DTC患者预后中的作用在国内尚未见文献报道。目的　评估ps-Tg、刺激性甲状腺球蛋白（s-Tg）和甲状腺球蛋白减少指数（TRI）对DTC（包括局部晚期DTC）患者131I治疗后长期缓解的预测价值，以期个性化管理不同预后的患者，减少预后良好者频繁接受随访的心理负担及经济负担。方法　2018年10月—2019年1月选取重庆医科大学附属遂宁市中心医院乳腺甲状腺外科建立的甲状腺癌患者长期随访的数据库中2004年1月—2012年1月在该院进行131I治疗的DTC患者992例。收集患者一般资料（包括性别、年龄、肿瘤直径、T/N/M分期、甲状腺侵袭情况、淋巴结破裂情况、ps-Tg、s-Tg、TRI）、预后情况。DTC患者预后的影响因素分析采用多因素Cox回归分析；绘制ps-Tg、s-Tg、TRI预测DTC、局部晚期DTC（T3~T4/Nx~N1期）患者长期缓解的受试者工作特征曲线（ROC曲线）；生存曲线的比较采用Log-rank检验。结果　多因素Cox回归分析结果显示，N分期、ps-Tg、s-Tg、TRI是DTC患者预后的影响因素（P<0.05）；T分期、N分期、ps-Tg情况、s-Tg情况、TRI是DTC患者预后的影响因素（P<0.05）。ps-Tg预测DTC患者长期缓解的ROC曲线下面积（AUC）为0.831，临界值为10.0 μg/L时，其灵敏度为74.1%，特异度为73.4%；s-Tg预测DTC患者长期缓解的AUC为0.846，临界值为1.0 μg/L时，其灵敏度为76.9%，特异度为74.7%；TRI预测DTC患者长期缓解的AUC为0.722，临界值为60.0%时，其灵敏度为77.7%，特异度为72.8%。ps-Tg预测局部晚期DTC患者长期缓解的AUC为0.864，临界值为10.0 μg/L时，其灵敏度为96.1%，特异度为55.4%；s-Tg预测局部晚期DTC患者长期缓解的AUC为0.859，临界值为1.0 μg/L时，其灵敏度为54.2%，特异度为97.3%；TRI预测局部晚期DTC患者长期缓解的AUC为0.764，临界值为62.5%时，其灵敏度为74.0%，特异度为63.8%。ps-Tg<10.0 μg/L的DTC患者长期缓解率高于ps-Tg≥10.0 μg/L的DTC患者（P<0.05）；s-Tg<1.0 μg/L的DTC患者长期缓解率高于s-Tg≥1.0 μg/L的DTC患者（P<0.05）；TRI>60.0%的DTC患者长期缓解率高于TRI≤60.0%的DTC患者（P<0.05）。ps-Tg<10.0 μg/L的局部晚期DTC患者长期缓解率高于ps-Tg≥10.0 μg/L的局部晚期DTC患者（P<0.05）；s-Tg<1.0 μg/L的局部晚期DTC患者长期缓解率高于s-Tg≥1.0 μg/L的局部晚期DTC患者（P<0.05）；TRI>62.5%的局部晚期DTC患者长期缓解率高于TRI≤62.5%的局部晚期DTC患者（P<0.05）。结论　当ps-Tg<10.0 μg/L、s-Tg<1.0 μg/L和TRI>60.0%时，可预测DTC患者131I治疗后能够长期缓解；对于局部晚期DTC（T3~T4/Nx~N1期）患者，ps-Tg<10.0 μg/L、s-Tg<1.0 μg/L和TRI>62.5%可预测其能够长期缓解。

关键词: 甲状腺肿瘤, 分化型甲状腺癌, 甲状腺球蛋白, 治疗前刺激性甲状腺球蛋白, 刺激性甲状腺球蛋白, 甲状腺球蛋白减少指数, 碘, 预测, 长期缓解