甲状腺乳头状癌术后患者TgAb水平变化及131I治疗疗效预测价值的研究

Study of TgAb levels dynamics and 131I therapeutic efficacy prediction value in postoperative papillary thyroid cancer patients

    摘要
  • 摘要:
    目的  探讨首次131I治疗前甲状腺球蛋白抗体（pa-TgAb）阳性的甲状腺乳头状癌（PTC）术后患者经131I治疗后甲状腺球蛋白抗体（TgAb）水平的变化趋势及其与疗效预测的关系。
    方法 回顾性分析2019年9月至2022年7月于天津医科大学总医院行手术后131I治疗的980例PTC患者，最终纳入pa-TgAb阳性（pa-TgAb水平≥40 IU/ml）且甲状腺球蛋白（Tg）水平<0.2 ng/ml的患者172例，其中男性33例、女性139例，年龄（44.2±12.1）岁。收集患者的临床资料、血清学和影像检查结果。根据131I清除残留甲状腺组织（简称清甲）治疗后6个月的TgAb水平将患者分为G1组（TgAb水平<40 IU/ml）和G2组（TgAb水平≥40 IU/ml），比较2组患者的清甲成功率，分析末次清甲成功患者的TgAb转阴时间。根据末次131I清甲治疗成功后pa-TgAb转阴时间将患者分为≤6个月组、7~12个月组、>12个月组、持续阳性组。根据末次131I清除手术不能切除的局部或远处转移癌灶（简称清灶）治疗后6个月的疗效评价将患者分为有效组和无效组，分析2组患者TgAb水平的变化（ΔTgAb）差异。计量资料的组间比较采用t检验或Mann-Whitney U检验。计数资料的组间比较采用χ2检验；采用多因素Logistic回归分析131I清甲治疗后TgAb转阴的影响因素；采用受试者工作特征（ROC）曲线评估131I清甲和131I清灶治疗相关因素对TgAb转阴的预测价值。
    结果 随访时间为24~46个月，中位随访时间为16.5个月。pa-TgAb阳性患者占17.6%（172/980）。142例行131I清甲治疗的患者中，失访10例（失访率为7.0%）。132例患者131I清甲治疗后6个月的131I清甲成功率为66.7%（88/132），G1组（76例）131I清甲成功率为75.0%（57/76），G2组（56例）131I清甲成功率为55.4%（31/56），2组的差异有统计学意义（χ2=7.724，P<0.01）。末次131I清甲治疗后6个月，131I清甲成功患者122例，其中112例患者的pa-TgAb在随访期内转阴，72.1%（88/122）的患者在6个月内转阴，11.5%（14/122）在7~12个月转阴，8.2%（10/122）在12个月以上转阴，达到疗效满意。多因素Logistic回归分析结果显示，pa-TgAb水平、桥本甲状腺炎、N分期、手术与首次131I清甲治疗时间间隔是清甲治疗后TgAb 6个月内转阴的影响因素（HR=0.998、4.054、0.414、0.989，均P<0.05）。30例伴有转移灶的患者行131I清灶治疗，失访2例（失访率为6.7%）；其中有效组患者20例、无效组8例。有效组ΔTgAb 0.76（0.64, 0.89）%与无效组ΔTgAb −0.03（−0.59, 0.21）%的差异有统计学意义（Z=−3.718，P<0.001）。ROC曲线分析结果表明，首次131I清甲治疗成功后，pa-TgAb水平<226 IU/ml且手术与首次131I清甲治疗时间间隔<62 d的pa-TgAb阳性PTC患者6个月内TgAb转阴的可能性较大；131I清灶治疗患者的pa-TgAb水平<473 IU/ml且ΔTgAb>62.0%时，预示疗效良好。
    结论  pa-TgAb水平、手术与首次131I清甲治疗时间间隔与131I清甲治疗的疗效密切相关，ΔTgAb可为预测患者131I清灶治疗的疗效提供参考依据。

     

    Abstract:
    Objective To investigate the change trend of thyroglobulin antibody (TgAb) level after radioiodine therapy and its predictive value for the initial 131I remnant ablation efficacy in postoperative papillary thyroid carcinoma (PTC) patients with pre-ablation TgAb (pa-TgAb) positivity.
    Methods Nine hundred and eighty PTC patients who received 131I therapy at Tianjin Medical University General Hospital from September 2019 to July 2022 were retrospective analyzed. Ultimately, 172 pa-TgAb positive (pa-TgAb level≥40 IU/ml) patients with Tg<0.2 ng/ml were enrolled (33 males, 139 females; age (44.2±12.1) years). Clinical data, serological results, and imaging findings were collected. Based on the TgAb levels six months after the 131I remnant ablation, the patients were divided into G1 group (TgAb level<40 IU/ml) and G2 group (TgAb level≥40 IU/ml). Successful ablation rates were compared between two groups. Based on the time it takes for pa-TgAb to turn negative after successful treatment with the last 131I remnant ablation, the patients were divided into ≤6 month group, 7–12 month group, >12 month group, and persistent positive group. Patients were categorized into response and non-response groups based on therapeutic efficacy evaluation at 6 months following the last 131I therapy for unresectable local or distant metastatic lesions (referred to as metastasis ablation) delta thyroglobulin antibodies (ΔTgAb) were compared between two groups. For continuous data, intergroup comparisons were performed using the t-test or Mann-Whitney U test. For categorical data, intergroup comparisons were performed using the χ2 test. Multivariate Logistic regression analysis was employed to investigate the influencing factors of TgAb conversion to negative after 131I remnant ablation. Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of factors related to 131I remnant ablation and 131I metastasis ablation for TgAb conversion to negative.
    Results The follow-up duration ranged from 24 to 46 months, with a median follow-up time of 16.5 months. The proportion of patients with positive pa-TgAb was 17.6%(172/980). Of the 142 patients who underwent 131I remnant ablation, 10 were lost to follow-up (a loss rate of 7.0%). Six months after the 131I remnant ablation of 132 patients, the success rate reached 66.7%(88/132). A significant difference was observed between G1 group (75.0%, 57/76) and G2 group (55.4%, 31/56) (χ2=7.724, P<0.01). Among the 122 patients with successful ablation after the last 131I remnant ablation, 112 achieved pa-TgAb seroconversion during the follow-up period, with values reaching 72.1%(88/122) within 6 months, 11.5% (14/122) at 7–12 months, and 8.2% (10/122) after 12 months, achieved satisfactory therapeutic effect. The results of the multivariate Logistic regression analysis showed that, pa-TgAb level, Hashimoto′s thyroiditis, N stage, and the interval between surgery and the initial 131I remnant ablation were influencing factors for TgAb turning negative within 6 months after 131I remnant ablation (HR=0.998, 4.054, 0.414, 0.989; all P<0.05). Thirty patients with metastatic lesions underwent 131I therapy, two patients were lost to follow-up (a loss rate of 6.7%); among them, 20 patients were in the response group and 8 patients were in the nonresponse group. The difference in ΔTgAb between the response group (0.76(0.64, 0.89)%) and the nonresponse group (−0.03(−0.59, 0.21)%) was statistically significant (Z=−3.718, P<0.001). The results of the ROC curves analysis indicated that after successful initial 131I remnant ablation, pa-TgAb positive PTC patients with pa-TgAb levels<226 IU/ml and interval between surgery and the initial 131I remnant ablation<62 days had a higher likelihood of TgAb conversion to negative within 6 months; patients undergoing 131I therapy with pa-TgAb levels<473 IU/ml and ΔTgAb>62.0% indicated good therapeutic efficacy.
    Conclusion The level of pa-TgAb, the interval between surgery were closely related to the efficacy of initial 131I remnant ablation, and ΔTgAb can provide a reference for predicting the therapeutic efficacy of 131I metastasis ablation in patients.

     

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