中高危DTC患者术后较高剂量131I治疗后疗效反应的影响因素分析

目的 探讨无转移的中高危分化型甲状腺癌（DTC）患者术后给予较高剂量131I治疗的疗效及其影响因素。 方法 回顾性分析2018年1月至2020年12月于山西医科大学第一医院行DTC全切术后的378例中高危DTC患者的临床资料，其中男性103例、女性275例，中位年龄45（13~85）岁。所有患者均在术后给予首次131I清甲和（或）辅助治疗，剂量3.70~5.55 GBq。同时131I治疗前行术后残留甲状腺99TcmO₄?显像，治疗后2~7 d行131I治疗后全身显像（Rx-WBS）。所有患者在131I治疗后至少6个月进行随访，中位随访时间16.3个月。依据2015年美国甲状腺协会（ATA）指南的疗效反应评估体系进行术后131I治疗疗效反应评估并分析影响因素。采用Spearman秩相关分析评估术后残留甲状腺99TcmO₄?显像靶/非靶比值(T/NT)与Rx-WBS评分的相关性；采用Mann-Whitney U检验、χ2检验或Fisher确切概率法分析所有观察指标在疗效满意（ER）组与疗效欠佳（nER）组间的差异是否有统计学意义；采用Logistic回归分析影响预后ER的独立危险因素，并绘制ROC曲线，获得最佳诊断临界值。 结果 ER组与nER组间在肿瘤最大径、术后刺激性甲状腺球蛋白（psTg）水平、N分期、术后与首次131I治疗间隔时间的差异均有统计学意义（Z=?7.127、?2.702，Fisher确切概率法， χ2=6.783，均P<0.05）；年龄、性别、被膜受累、肿瘤多灶性、T分期、复发风险分层、首次131I治疗剂量、TSH水平、尿碘水平、甲状腺99TcmO₄?显像半定量指标T/NT、131I Rx-WBS评分的差异均无统计学意义（Z=?1.505~?0.664， χ2=0.064~5.501，Fisher确切概率法，均P>0.05）。Spearman 秩相关检验分析结果显示，99TcmO₄?显像T/NT与Rx-WBS显像评分呈中度相关(r=0.530，P<0.001)。多因素Logistic回归分析结果显示，psTg水平是预后ER的独立危险因素。ROC曲线分析结果显示，psTg水平预测ER的最佳临界值为5.90 ng/ml、灵敏度为83.76%、特异度为59.81%。 结论 给予较高剂量131I治疗的中高危DTC患者，不论甲状腺99TcmO₄?显像提示残留甲状腺多少均可以得到同样的ER比率；且术后2个月内行首次131I治疗，可能获得更好的治疗疗效。另外，psTg是预测无转移中高危DTC患者临床ER的独立危险因素。

Therapeutic response outcomes and influencing factors after surgery and a higher does of 131I in patients with intermediate-to-high risk differentiated thyroid cancer

Objective To investigate the efficacy response and influencing factors of higher dose 131I in patients with metastasis-free intermediate-to-high risk differentiated thyroid cancer (DTC). Methods The clinical date of 378 patients with intermediate-to-high risk DTC who attended in the First Hospital of Shanxi Medical University from January 2018 to December 2020 were retrospectively analyzed. The patients included 103 male and 275 female with a median age of 45(13–85) years. All patients were given the first 131I remnant ablation and/or adjuvant therapy at a dose range of 3.70–5.55 GBq. Postoperative residual thyroid 99TcmO₄? image was performed before 131I treatment, and 131I post-treatment whole body scan (Rx-WBS) was performed 2–7 days after treatment. All patients were followed up at least 6 months with a median follow-up time of 16.3 months. The efficacy response evaluation system was evaluated according to the 2015 American Thyroid Association assessment system, and its influencing factors were analyzed. Spearman rank correlation analysis was used to evaluate the correlation between 99TcmO₄? image target/non-target (T/NT) ratio and Rx-WBS score.The Mann-Whitney U test, χ2 test or Fisher's exact probability method was utilized to analyze whether the difference between the excellent response (ER) and non-excellent response (nER) groups was statistically significant for all observed indicators. Binary multivariate Logistic regression was used to analyze the independent influencing factors of prognostic ER, receiver operator characteristic (ROC) curves were utilized to obtain optimal diagnostic thresholds. Results Stistically significant differences were observed in maximum tumor diameter, postoperative stimulated thyroglobulin (psTg) level, N stage, and interval time between the two groups of ER and nER (Z=?7.127, ?2.702, Fisher's exact probability method, χ2=6.783; all P<0.05). The differences were statistically insignificant for age, sex, capsule involvement, tumor multifocality, T-staging, risk of recurrence stratification, first dose of 131I treatment, thyroid-stimulating hormone (TSH) level, urinary iodine level, 99TcmO₄? image T/NT values, and Rx-WBS score (Z=?1.505 to ?0.664, χ2=0.064–5.501, Fisher's exact probability method; all P>0.05). Spearman rank correlation analysis showed a moderate correlation between 99TcmO₄? image T/NT values and Rx-WBS imaging scores (r=0.530, P<0.001). A multivariate Logistic regression analysis showed that psTg level was the independent risk factor of ER. The ROC curve analysis showed that the optimal cut-off value of ER was 5.90 ng/ml, the sensitivity was 83.76%, and the specificity was 59.81%. Conclusions Patients with intermediate-to-high risk DTC treated with higher dose of 131I had the same good ER proportion regardless of the amount of residual thyroid indicated by thyroid 99TcmO₄? imaging. Patients receiving 131I treatment within 2 months after surgery may obtain better ER proportion. Meanwhile, psTg was an independent risk factor for predicting ER proportion in patients with metastasis-free intermediate-to-high risk DTC.