阿帕替尼治疗局部晚期/进展性碘难治性分化型甲状腺癌的血清学反应评估  

Serologically biochemical evaluation for patients with locally advanced/metastatic radioactive iodine-refractory differentiated thyroid cancer treated by apatinib

作　　者：孙郁青 慕转转 魏星 张鑫 王湘 林岩松 Sun Yuqing;Mu Zhuanzhuan;Wei Xing;Zhang Xin;Wang Xiang;Lin Yansong(Department of Nuclear Medicine,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine State Key Laboratory of Complex Severe and Rare Diseases(Peking Union Medical College Hospital),Beijing 100730,China;Department of Oncology,Peking University International Hospital,Beijing 102200,China;Department of Medical Oncology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院、北京协和医学院北京协和医院核医学科、核医学分子靶向诊疗北京市重点实验室、疑难重症及罕见病国家重点实验室(北京协和医院),北京100730 [2]北京大学国际医院肿瘤内科,北京102200 [3]中国医学科学院、北京协和医学院北京协和医院肿瘤内科,北京100730

出　　处：《中华核医学与分子影像杂志》2022年第11期644-649,共6页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：中国医学科学院医学与健康科技创新工程(2020-I2M-2-003);国家重点研发计划"政府间国际科技创新合作/港澳台科技创新合作"重点专项(2019YFE0106400)。

摘　　要：目的分析碘难治性分化型甲状腺癌(RAIR-DTC)患者阿帕替尼治疗过程中的血清学疗效反应与传统结构影像学疗效评价的疾病进展趋势及预后的关系。方法回顾性分析2016年3月至2022年6月就诊于北京协和医院行阿帕替尼治疗局部进展和(或)转移性RAIR-DTC的Ⅱ期临床试验患者19例,其中男9例、女10例,年龄46.0(41.0,57.5)岁。探讨血清甲状腺球蛋白(Tg)变化与实体瘤疗效评价标准1.1(RECIST 1.1)结构影像学疗效评估及疾病进展趋势的关系;探讨剂量调整后Tg变化和结构影像学上靶病灶最大径变化的关系。采用Mann-WhitneyU检验、Wilcoxon符号秩检验分析数据。结果(1)中位随访49.41个月,19例患者基线期Tg为363.20(13.08,2490.50)μg/L,血清Tg治疗响应时间为0.47(0.47,0.98)个月,依据RECIST 1.1标准的靶病灶治疗响应时间为1.80(1.30,1.90)个月。初始治疗2周、4周、8周后,全队列中位Tg分别下降38.68%、64.70%和78.94%,8周后中位靶病灶最大径缩小幅度为33.48%。根据患者最佳疗效反应,将其分为部分缓解(PR)组(15例)和疾病稳定(SD)组(4例),PR组与SD组患者中位Tg下降幅度分别为87.00%与28.79%,相应组别中位靶病灶最大径缩小幅度分别为45.00%与21.22%。据末次疗效评估,将患者分为疾病进展(PD)组(13例)和非PD(包括PR和SD)组(5例),PD组患者中位Tg升高幅度大于非PD组(381.55%与175.43%;U=10.00,P=0.037)。第1次剂量调整后,Tg升高幅度与对应靶病灶最大径增大幅度分别为167.31%与2.14%,第2次剂量调整后两者分别为231.06%与9.73%。第1次剂量调整前后Tg变化及对应靶病灶最大径变化的差异均有统计学意义(z值:-3.06和-2.23,P值:0.002和0.026)。结论在阿帕替尼治疗RAIR-DTC中,相较于传统影像学(RECIST 1.1),Tg可更灵敏地反映阿帕替尼疗效及疾病进展趋势。Objective To analyze the relationship between serologically biochemical response and the disease progression trend and prognosis evaluated by traditional structural imaging in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC)treated by apatinib.Methods A retrospective study was performed on apatinib-treated(phaseⅡ)patients(n=19;9 males,10 females;age 46.0(41.0,57.5)years)with locally advanced/metastatic RAIR-DTC in Peking Union Medical College Hospital from March 2016 to June 2022.The relationships between serum thyroglobulin(Tg)and response evaluation criteria in solid tumors(RECIST)1.1 structural imaging efficacy evaluation and disease progression trend were analyzed.The relationships between change of Tg after dose adjustment and the change of maximum diameter of target lesions in structure imaging were also discussed.Mann-Whitney U test and Wilcoxon signed-rank test were used to analyze the data.Results During the median 49.41 months follow-up,the baseline Tg was 363.20(13.08,2490.50)μg/L.The Tg time-to-response was 0.47(0.47,0.98)months,which was 1.80(1.30,1.90)months for RECIST 1.1.After 2,4 and 8 weeks of initial treatment,the median Tg of the whole cohort decreased by 38.68%,64.70%and 78.94%,respectively.After 8 weeks,the reducing degree of maximum diameter of target lesions was 33.48%.According to the best response,patients were divided into two groups:partial response(PR)group(n=15)and stable disease(SD)group(n=4).The median decreasing degree of Tg in PR group and that in SD group were 87.00%and 28.79%,and the reducing degree of maximum diameter of target lesions in corresponding groups were 45.00%and 21.22%.According to the final efficacy evaluation,patients were further divided into two groups:progressive disease(PD)group(n=13)and non-PD(including PR and SD)group(n=5).The median increasing degree of Tg in PD group was higher than that in non-PD group(381.55%vs 175.43%;U=10.00,P=0.037).The increasing degree of Tg and that of the maximum diameter of target lesions we

关 键 词：甲状腺肿瘤 分子靶向治疗 药物疗法 甲状腺球蛋白 实体肿瘤疗效评价标准 预后 

分 类 号：R736.1[医药卫生—肿瘤]