安罗替尼对进展期放射性碘难治性分化型甲状腺癌的疗效及对病灶摄碘功能的影响

Efficacy of anlotinib in the treatment of advanced radioactive iodine-refractory differentiated thyroid cancer and the effect on iodine uptake of lesions

目的研究安罗替尼对进展期放射性碘难治性分化型甲状腺癌(RAIR-DTC)的疗效、安全性及对病灶摄碘功能的影响。方法回顾性分析2019年1月至2023年2月于聊城市人民医院行安罗替尼治疗且符合入组标准的进展期RAIR-DTC患者23例,其中男10例、女13例,年龄(59.1±8.7)岁。在安罗替尼治疗期间,每6周复查患者甲状腺功能、血清甲状腺球蛋白(Tg)及Tg抗体(TgAb),每12周通过CT监测靶病灶(TL)最大径变化,进行疗效评价,并记录治疗相关不良反应。对部分患者行诊断性^(131)I显像(Dx-WBS),以评估治疗后病灶摄碘功能的变化。本研究分析患者24周内的治疗后变化,组间比较行Friedman检验,进一步成对比较时,P值经Bonferroni法校正。结果安罗替尼治疗24周,23例患者中8例达部分缓解,15例疾病稳定,没有患者达到完全缓解。安罗替尼治疗6、12、18、24周,患者Tg水平[189.5(85.0,483.3)、127.7(52.4,319.8)、82.0(40.2,213.5)、80.1(39.9,205.0)μg/L较基线Tg水平[384.5(210.9,1605.0)μg/L]明显下降(χ^(2)值:4.23~7.86,均P<0.001);治疗12周与治疗18周血清Tg水平差异有统计学意义(χ^(2)=3.06,P<0.001),治疗18周与24周差异无统计学意义(χ^(2)=12.57,P=0.059)。治疗12、24周患者肺及颈部淋巴结TL最大径较基线水平明显缩小(^(2)14.76~31.12,均P<0.001),治疗12周和24周上述TL最大径无明显差异(χ^(2)值:5.65、9.02,P值:0.314、0.070)。常见不良反应包括高血压、手足综合征、高三酰甘油血症及蛋白尿,未出现4级以上不良反应以及与不良反应相关的死亡事件。7例患者在安罗替尼治疗后行Dx-WBS评估,均未发现病灶摄碘功能的改变。结论安罗替尼对进展期RAIR-DTC有明确的疗效且不良反应较小,该药疗效在12~18周达到最强,24周趋于稳定。未发现安罗替尼有诱导RAIR-DTC细胞再分化、提高摄碘能力的作用。

ObjectiveTo study the efficacy and safety of anlotinib in the treatment of advanced radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC)and the effect of anlotinib on iodine uptake of lesions.MethodsA retrospective analysis was performed on 23 patients(10 males and 13 females,age(59.1±8.7)years)with advanced RAIR-DTC who were treated with anlotinib in Liaocheng Hospital Affiliated to Shandong First Medical University between January 2019 and February 2023 and met the enrollment criteria.Thyroid function,serum thyroglobulin(Tg)and Tg antibody(TgAb)were determined every 6 weeks during the treatment with anlotinib,and maximum diameter of target lesion(TL)was monitored by CT every 12 weeks,in order to evaluate the therapeutic efficacy,and treatment-related adverse reactions were observed.Diagnostic ^(131)I whole body scan(Dx-WBS)was performed in some patients to evaluate the changes in iodine uptake of lesions after anlotinib treatment.In this study,the posttreatment changes of patients within 24 weeks during the treatment were analyzed.The maximum diameter of TL and Tg at different time points were compared by Friedman test,and were further compared in pairs with P values corrected by Bonferroni method.ResultsAfter 24 weeks of treatment with anlotinib,8 of 23 patients achieved partial response,15 had stable disease,and no patients achieved complete response.Serum Tg levels at 6,12,18,24 weeks after anlotinib treatment were 189.5(85.0,483.3),127.7(52.4,319.8),82.0(40.2,213.5)and 80.1(39.9,205.0)μg/L,all of which were lower than the baseline level of Tg(384.5(210.9,1605.0)μg/L;χ^(2) values:4.23-7.86,all P<0.001).Tg level at 18 weeks after treatment was statistically different from that at 12 weeks after treatment(χ^(2)=3.06,P<0.001),but was not statistically different from that at 24 weeks after treatment(χ^(2)=12.57,P=0.059).The maximum TL diameters of lung and cervical lymph nodes were significantly reduced at week 12 and 24 of anlotinib treatment compared with baseline(χ^(2) values:14.76-31.12,all P<0.001),while there was no significant difference in TL maximum diameter at 12 and 24 weeks of treatment(χ^(2) values:5.65,9.02,P values:0.314,0.070).Common adverse reactions included hypertension,hand-foot syndrome,hyperacylglyceremia and proteinuria.No adverse reactions above grade 4 or death related to adverse reactions occurred.Dx-WBS evaluation was performed in 7 patients after anlotinib treatment,and no change in iodine uptake was found.ConclusionsAnlotinib has a clear effect on advanced RAIR-DTC with less adverse reactions.The efficacy of anlotinib reaches the strongest at around 12-18 weeks and becomes stable at 24 weeks.No effect of anlotinib on inducing redifferentiation of RAIR-DTC cells and enhancing iodine uptake is found.