^(131)I辅助治疗对BRAF^(V600E)突变型非远处转移性甲状腺乳头状癌患者疗效的初步探讨

Preliminary study of ^(131)I adjuvant therapy in BRAF^(V600E)mutant patients with non-distant metastatic papillary thyroid cancer

目的探讨^(131)I辅助治疗对B-Raf原癌基因丝/苏氨酸蛋白激酶(BRAF)^(V600E)突变型非远处转移性甲状腺乳头状癌(PTC)患者的长期治疗疗效反应。方法回顾性分析2008年1月至2019年1月间就诊于北京协和医院仅行1次^(131)I治疗且临床、随访(中位随访时间63个月)及评估资料完整的181例非远处转移性PTC患者[男65例,女116例,年龄(38.9±11.8)岁]资料。按其原发灶BRAFV600E基因是否突变分为突变型组和野生型组;根据^(131)I治疗剂量的不同,分为清除残留甲状腺组织(简称清甲)治疗组(1.1 GBq)和辅助治疗组(3.7~5.5 GBq)。采用两独立样本t检验、Mann-WhitneyU检验和χ^(2)检验比较各组患者的临床、病理特征及^(131)I治疗后长期治疗疗效反应。结果BRAFV600E突变型患者(n=150)的^(131)I治疗前刺激性甲状腺球蛋白(ps-Tg)水平明显高于野生型[n=31;6.32(0.90,8.70)与3.92(0.40,4.40)μg/L;z=-2.413,P=0.016],但2组的其余临床病理特征(包括年龄、性别、肿瘤大小、多灶性、被膜侵犯、N分期)差异均无统计学意义(t=-0.663,z=-1.151,χ^(2)值:0.003~1.491,均P>0.05),2组的治疗疗效反应差异也无统计学意义(χ^(2)=1.094,P=0.778)。81例接受^(131)I辅助治疗的患者中,突变型组(n=69)的ps-Tg水平高于野生型组[n=12;8.70(1.30,11.80)与3.40(0.30,4.50)μg/L;z=-2.194,P=0.028];但2组的治疗疗效反应差异无统计学意义(χ^(2)=1.792,P=0.617)。BRAFV600E突变型患者中,与清甲治疗组(n=81)相比,辅助治疗组(n=69)肿瘤较大[1.52(0.95,2.00)与1.21(0.60,1.50)cm;z=-2.728,P=0.006]、N分期较晚(χ^(2)=11.460,P=0.003)、ps-Tg水平较高[8.70(1.30,11.80)与4.34(0.50,5.30)μg/L;z=-3.314,P=0.001],但2组的治疗疗效反应差异无统计学意义(χ^(2)=6.478,P=0.091)。结论^(131)I辅助治疗有助于改善肿瘤较大、淋巴结分期较晚、ps-Tg水平较高的BRAFV600E突变型非远处转移性PTC患者的较长期治疗疗效反应。

Objective To evaluate ^(131)I adjuvant therapy in B-Raf proto-oncogene,serine/threonine kinase(BRAF)^(V600E) mutant patients with non-distant metastatic papillary thyroid cancer(PTC).Methods From January 2008 to January 2019,a total of 181 PTC patients(65 males,116 females,age:(38.9±11.8)years)with non-distant metastases from Peking Union Medical College Hospital were retrospectively enrolled.All patients received only one time ^(131)I therapy with complete clinicopathological information,data of follow-up(median time:63 months)and assessment of response to therapy.Patients were divided into mutant and wild type group in terms of BRAFV600E status or ablation group(1.1 GBq)and adjuvant therapy group(3.7-5.5 GBq)in terms of different ^(131)I dosage.Clinicopathological features and the response to therapy were compared between different groups by using independent-sample t test,Mann-Whitney U test andχ^(2) test.Results The levels of preablative stimulated thyroglobulin(ps-Tg)in the BRAFV600E mutant type group(n=150)was significantly higher than that in the wild type group(n=31;6.32(0.90,8.70)vs 3.92(0.40,4.40)μg/L;z=-2.413,P=0.016),however,there were no significant differences in other clinicopathological characteristics(including age,sex,tumor size,multifocality,capsule invasion and N staging)between the two groups(t=-0.663,z=-1.151,χ^(2) values:0.003-1.491,all P>0.05)and the therapeutic response was also not different between the two groups(χ^(2)=1.094,P=0.778).Of 81 patients who received ^(131)I adjuvant therapy,the ps-Tg level of BRAFV600E mutant type group(n=69)was higher than that of the wild type group(n=12;8.70(1.30,11.80)vs 3.40(0.30,4.50)μg/L;z=-2.194,P=0.028),while the therapeutic response was not different between the two groups(χ^(2)=1.792,P=0.617).Compared with BRAFV600E mutant patients received ^(131)I ablation(n=81),BRAFV600E mutant patients received ^(131)I adjuvant therapy(n=69)had larger tumors(1.52(0.95,2.00)vs 1.21(0.60,1.50)cm;z=-2.728,P=0.006),more advanced N staging(χ^(2)=11.460,P=0.003)and higher ps-Tg level(8.70(1.30,11.80)vs 4.34(0.50,5.30)μg/L;z=-3.314,P=0.001),but the therapeutic response was not different between the two groups(χ^(2)=6.478,P=0.091).Conclusion ^(131)I adjuvant therapy may improve the longer-term response to therapy in BRAFV600E mutant PTC patients with lager tumors,more advanced N staging and higher ps-Tg level.