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目前,手术切除联合131I及甲状腺激素抑制剂的综合治疗对DTC有较好的治疗效果,但因颈部淋巴结分布较为广泛,DTC的淋巴结转移率较高[1]。中国临床肿瘤学会(CSCO)持续/复发及转移性分化型甲状腺癌诊疗指南-2019[2]指出,对于存在淋巴结转移的DTC患者,需进一步实施清灶治疗,因此明确是否存在淋巴结转移灶具有重要意义。131I是DTC患者术后清除残余甲状腺组织(简称清甲)的重要手段,由于碘是甲状腺激素合成的原料,因此通过测定甲状腺的碘摄取率,可判断甲状腺功能,确定给药剂量[3]。目前国内医师普遍认为固定大剂量131I是获得良好清甲效果的有效手段,但碘摄取率受甲状腺残余情况、患者年龄等多个因素的影响,其是否可对DTC患者术后首次131I治疗反应进行有效预测有待进一步探究[4-5]。SPECT/CT是一种多模态显像技术,可在CT图像的基础上提供病理生理信息,对于DTC患者术后可疑淋巴结转移病灶的判断有较高的灵敏度[6-7]。本研究旨在评价SPECT/CT淋巴结显像与碘摄取率在预测DTC首次131I治疗反应中的价值。
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回顾性分析2021年1月至2022年1月于湖北医药学院附属随州医院首次接受131I治疗的138例DTC术后患者的临床资料及影像资料,其中男性36例、女性102例,年龄(47.8±9.8)岁。纳入标准:符合中国临床肿瘤学会(CSCO)持续/复发及转移性分化型甲状腺癌诊疗指南-2019[2]对甲状腺癌的诊断;接受甲状腺根治术,术后组织病理学结果为DTC;术后首次行131I治疗。排除标准:妊娠期与哺乳期女性;合并其他部位肿瘤;甲状腺癌术后创面未愈合者。138例患者中,甲状腺乳头状癌、滤泡状癌分别为128例、10例,术中甲状腺全切、近全切者分别为98例、40例。所有患者均在检查前签署了知情同意书。本研究符合《赫尔辛基宣言》的原则。
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患者于131I治疗前4周禁碘,停止服用甲状腺激素类药物,血清TSH水平>30 mU/L,并检测游离甲状腺原氨酸(free triiodothyronine,FT3)、游离甲状腺素(free thyroxine,FT4)、治疗前刺激性甲状腺球蛋白(preablation stimulated thyroglobulin,psTg)水平,行甲状腺彩超(美国GE公司LOGIQ E9型)观察残余甲状腺情况及局部淋巴结转移情况。给予患者131I治疗剂量3.70~7.40 GBq,空腹一次性口服,存在周围软组织侵犯、肺或淋巴结转移等情况的患者的治疗剂量为5.55 GBq,骨转移患者的治疗剂量为7.40 GBq,行甲状腺切除后残余甲状腺组织较多的患者的治疗剂量可减少至2.96 GBq[8]。
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患者服用131I后5~10 d内行131I全身显像(whole body scan,WBS)、SPECT/CT(德国西门子公司Symbia T16型)扫描,使用高能平行孔准直器,能峰360 keV,窗宽10%,扫描速度15 cm/min,范围自鼻咽部至主动脉弓,矩阵128×128,CT层厚1.25 mm,管电流100 mA,管电压120 keV,在后台工作站勾画ROI并完成图像融合,结合CT图像测量扫描范围内最大淋巴结短径并记录。由1名具有5年以上工作经验的核医学科医师和1名中级以上职称的放射科医师共同阅片,意见不一致时由主任医师阅片判定。
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患者服用131I 24 h后使用甲状腺功能仪(安徽中科中佳科学仪器有限公司 NM-6110型)测定碘摄取率。测定碘摄取率前先测定室内本底计数率和颈模内标准源计数率,使甲状腺位于中心视野,测量3次取平均值,使用公式(1)计算碘摄取率:
$ 碘摄取率 = \frac{甲状腺部位计数-本底计数}{标准源计数-本底计数}\times100\%$ -
患者首次131I治疗后至少随访6个月,根据131I治疗分化型甲状腺癌指南(2021版)[9] 进行疗效反应的评价。疗效满意(excellent response,ER):在甲状腺球蛋白抗体(TgAb)为阴性的情况下,刺激性甲状腺球蛋白水平<1 μg/L,抑制性甲状腺球蛋白水平<0.2 μg/L,且影像学检查未发现阳性病灶;疗效不确切(indeterminate response,IDR):在甲状腺球蛋白抗体(TgAb)水平较低或者持续下降的情况下,0.2 μg/L<抑制性甲状腺球蛋白水平<1 μg/L,1 μg/L<刺激性甲状腺球蛋白水平<10 μg/L,影像学检查未发现结构或功能性病变,131I治疗后131I全身显像示颈部甲状腺床区稍显影;生化疗效不佳(biochemical incomplete response,BIR):刺激性甲状腺球蛋白水平≥10 μg/L或抑制性甲状腺球蛋白水平≥1 μg/L或甲状腺球蛋白抗体(TgAb)水平持续上升,影像学检查未发现阳性病灶;结构性疗效不佳(structural incomplete response,SIR):影像学检查发现阳性病灶,存在结构或功能性病变。分组依据:符合ER标准的病例,治疗效果满意,归入ER组;符合IDR、BIR及SIR标准的病例治疗效果不满意,归入非ER组。
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应用SPSS 25.0软件对数据进行统计学分析。符合正态分布的计量资料以
$ \bar x \pm {{s}} $ 表示,组间比较采用独立样本t检验(方差齐),不符合正态分布的计量资料以M(Q1, Q3)表示,组间比较采用Mann-Whitney U检验。计数资料以%表示,组间比较采用χ2检验。采用单因素Logistic回归分析筛选出有统计学意义的指标作为自变量,采用多因素Logistic回归分析确定DTC首次131I疗效反应不满意的预测因素,以ROC曲线获得131I疗效影响因素的最佳临界值,以AUC判断预测因素对治疗反应的预测价值。P<0.05为差异有统计学意义。 -
138例患者中有102例患者在首次131I治疗后达到ER,归入ER组,36例为IDR、BIR及SIR,归入非ER组。由表1可知,ER组在患者性别、原发肿瘤长径、病理类型、手术切除方式、首次131I剂量与非ER组比较,差异均无统计学意义(均P>0.05);非ER组腺外浸润占比、TNM分期 Ⅲ~Ⅳ期占比、复发风险分层中/高风险占比、psTg水平和淋巴结短径均高于ER组,治疗前TSH水平与碘摄取率均低于ER组,差异均有统计学意义(均P<0.05)。
临床资料 疗效满意组(n=102) 非疗效满意组(n=36) 检验值 P值 性别 χ2=1.984 0.159 男(例,%) 25(24.51) 11(30.56) 女(例,%) 77(75.49) 25(69.44) 原发肿瘤长径(cm, )$ \bar x \pm {{s}} $ 1.41±0.30 1.52±0.35 t=−1.809 0.073 病理类型 χ2=0.030 0.861 乳头状癌(例,%) 93(91.18) 35(97.22) 滤泡状癌(例,%) 9(8.82) 1(2.78) 治疗前TSH水平[mU/L,M(Q1,Q3)] 65.33(42.41,120.33) 59.10(35.32,118.33) Z=6.861 <0.001 腺外浸润 χ2=8.257 0.004 有(例,%) 37(36.27) 23(63.89) 无(例,%) 65(63.73) 13(36.11) TNM分期 χ2=6.829 0.009 Ⅰ~Ⅱ(例,%) 57(55.88) 11(30.56) Ⅲ~Ⅳ(例,%) 45(44.12) 25(69.44) 复发风险分层 χ2=7.461 0.006 低风险(例,%) 32(31.37) 3(8.33) 中/高风险(例,%) 70(68.63) 33(91.67) 手术切除方式 χ2=1.422 0.233 全切(例,%) 68(66.67) 30(83.33) 近全切(例,%) 34(33.33) 6(16.67) psTg水平 [μg/L,M(Q1, Q3)] 1.32(0.65,1.66) 1.65(0.90,1.87) Z=4.683 <0.001 首次131I治疗剂量(GBq, )$ \bar x \pm {{s}} $ 5.35±1.43 5.88±0.61 t=1.888 0.061 淋巴结短径(mm, )$ \bar x \pm {{s}} $ 4.52±1.43 6.33±2.01 t=5.837 <0.001 碘摄取率(%, )$ \bar x \pm {{s}} $ 8.65±2.33 5.63±1.50 t=5.314 <0.001 注:TSH为促甲状腺激素;TNM为肿瘤、淋巴结、转移;psTg为治疗前刺激性甲状腺球蛋白 表 1 138例分化型甲状腺癌患者首次131I治疗的反应结果及临床资料的单因素Logistic回归分析
Table 1. Results and clinical data univariate Logistic regression analysis of 138 patients with differentiated thyroid carcinoma treated with 131I for the first time
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以单因素Logistic回归分析有统计学意义的指标作为自变量,DTC术后首次131I治疗反应不满意作为因变量,经对连续变量(治疗前TSH水平、psTg水平、淋巴结短径和碘摄取率)及二分类变量(腺外浸润、TNM分期、复发风险分层)赋值后行多因素Logistic回归分析,结果显示,治疗前TSH水平、腺外浸润占比、TNM分期Ⅲ~Ⅳ期占比、复发风险分层中/高风险、psTg水平、淋巴结短径、碘摄取率是DTC患者术后首次131I疗效反应不满意的预测因素(表2)。
变量 回归系数 标准误 Wald值 OR值 95%CI P值 治疗前TSH水平 1.544 0.272 30.982 4.545 2.251~6.354 <0.001 腺外浸润占比 0.887 0.263 11.375 3.012 1.526~4.857 <0.001 TNM分期Ⅲ~Ⅳ期占比 0.785 0.270 8.453 2.192 1.322~3.560 <0.001 复发风险分层中/高风险 0.663 0.288 5.300 1.941 0.948~3.251 0.001 psTg水平 0.912 0.252 13.098 2.489 1.653~5.012 <0.001 淋巴结短径 1.314 0.257 26.141 3.721 2.013~6.217 <0.001 碘摄取率 1.135 0.298 14.506 3.511 1.858~5.624 <0.001 常量 −10.325 1.245 71.852 0.000 − − 注:−表示无此项数据。TSH为促甲状腺激素;TNM为肿瘤、淋巴结、转移;psTg为治疗前刺激性甲状腺球蛋白;CI为置信区间 表 2 138例分化型甲状腺癌患者首次131I治疗疗效反应不满意预测因素的多因素Logistic回归分析
Table 2. Multivariate Logistic regression analysis of predictors of unsatisfactory response to 131I treatment for the first time in 138 patients with differentiated thyroid carcinoma
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ROC曲线分析结果显示,SPECT/CT显像的淋巴结短径最大约登指数对应的临界值为5.52 mm,预测DTC患者首次131I疗效反应不满意的AUC为0.766;碘摄取率最大约登指数对应的临界值为7.47%,AUC为0.749,二者联合预测的AUC为0.911;二者联合预测DTC患者首次131I治疗反应的AUC均高于单独预测,差异均有统计学意义(均P<0.01)(图1、表3)。
图 1 SPECT/CT显像的淋巴结短径及碘摄取率对分化型甲状腺癌患者首次131I疗效反应预测的受试者工作特征曲线
Figure 1. Receiver operating characteristic curve of SPECT/CT developed lymph node diameter and iodine uptake rate for predicting the response to the first 131I curative effect in differentiated thyroid carcinoma patients
指标 AUC 95%CI P值 临界值 灵敏度(%) 特异度(%) 约登指数 淋巴结短径(mm) 0.766 0.687~0.834 <0.001 5.52 78.43 72.22 0.507 碘摄取率(%) 0.749 0.669~0.819 <0.001 7.47 64.71 88.89 0.536 淋巴结短径+碘摄取率 0.911 0.850~0.953 <0.001 − 99.02 83.33 0.823 注:−表示无此项数据。SPECT为单光子发射计算机体层摄影术;CT为计算机体层摄影术;AUC为曲线下面积;CI为置信区间 表 3 SPECT/CT显像的淋巴结短径及碘摄取率对分化型甲状腺癌患者首次131I治疗反应疗效不满意的预测结果
Table 3. Predictive results of SPECT/CT lymph node short diameter and iodine uptake rate on non-excellent response response to the first 131I treatment in differentiated thyroid carcinoma patients
SPECT/CT淋巴结显像与碘摄取率预测DTC首次131I治疗反应的价值
Value of SPECT/CT lymph node imaging and iodine uptake rate in predicting the response of DTC to the first 131I treatment
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摘要:
目的 探究SPECT/CT与碘摄取率预测分化型甲状腺癌(DTC)首次131I治疗反应的价值。 方法 回顾性分析2021年1月至2022年1月于湖北医药学院附属随州医院首次接受131I治疗的138例DTC术后患者的临床资料及影像资料,其中男性36例、女性102例,年龄(47.8±9.8)岁。所有患者均行131I全身显像和SPECT/CT显像,测定碘摄取率。患者在131I治疗后随访至少6个月进行疗效反应评价,将患者分为疗效满意(ER)组和非ER组。2组间临床资料的比较采用独立样本t检验、Mann-Whitney U检验和χ2检验, 采用Logistic回归分析明确DTC首次131I治疗疗效反应不满意的预测因素,采用受试者工作特征(ROC)曲线获得最佳临界值,以曲线下面积(AUC)判断预测因素对治疗反应的预测价值。 结果 非ER组患者腺外浸润占比(63.89% 对 36.27%)、肿瘤、淋巴结、转移(TNM)分期 Ⅲ~Ⅳ期占比(69.44% 对44.12%),复发风险分层中/高风险占比(91.67% 对 68.63%)、治疗前刺激性甲状腺球蛋白(psTg)水平[1.65(0.90,1.87) μg/L对 1.32(0.65,1.66) μg/L]和淋巴结短径[(6.33±2.01) mm 对 (4.52±1.43) mm]均高于ER组,治疗前促甲状腺激素(TSH)水平[59.10(35.32,118.33) mU/L对 65.33(42.41,120.33) mU/L]与碘摄取率[(5.63±1.50)% 对(8.65±2.33)%]均低于ER组,差异均有统计学意义(t=5.314、5.837,χ2=6.829~8.257,Z=4.683、6.861;均P<0.05)。多因素Logistic回归分析结果显示,DTC患者术后首次131I疗效反应不满意预测因素为治疗前TSH水平、腺外浸润占比、TNM分期 Ⅲ~Ⅳ期占比、复发风险分层中/高风险、psTg水平、淋巴结短径、碘摄取率(OR=1.941~4.545,均P<0.01)。ROC曲线分析结果显示,SPECT/CT淋巴结短径最大约登指数对应的临界值为 5.52 mm,预测DTC首次131I疗效反应不满意的AUC为0.766(95%CI:0.687~0.834);碘摄取率最大约登指数对应的临界值为7.47%,AUC为0.749(95%CI:0.669~0.819),二者联合的AUC为0.911(95%CI:0.850~0.953);二者预测DTC首次131I治疗反应的AUC均高于单独预测的AUC,且差异均有统计学意义(均P<0.001)。 结论 SPECT/CT显像淋巴结短径与碘摄取率对于预测DTC首次131I治疗效果均有一定的价值,二者联合使用的预测价值更优。 -
关键词:
- 体层摄影术,发射型计算机,单光子 /
- 体层摄影术,X线计算机 /
- 分化型甲状腺癌 /
- 碘摄取率 /
- 碘放射性同位素 /
- 淋巴结
Abstract:Objective To analyze the value of SPECT/CT and iodine uptake rate in predicting response to the first 131I treatment of patients with differentiated thyroid carcinoma (DTC). Methods From January 2021 to January 2022, 138 postoperative patients with DTC who received 131I treatment for the first time in Suizhou Hospital, Hubei University of Medicine were retrospectively analyzed, including 36 males and 102 females aged (47.8±9.8) years. All patients underwent 131I whole-body scan and SPECT/CT imaging, determine the iodine uptake rate. After 131I treatment, the patients were followed up for at least 6 months to evaluate efficacy and response. The patients were divided into the excellent response (ER) group and non-ER group. Comparison of clinical data between the two groups select independent sample t-test, Mann Whitney U test, χ2 conduct analysis, and Logistic regression analysis were used to identify the predictors of the unsatisfactory response to the first 131I therapy in patients with DTC. In addition, the receiver operating characteristic (ROC) curve was used to obtain the best critical value, and the area under curve (AUC) was used to determine the predictive value of predictive factors on treatment response. Results The proportion of extraglandular invasion (63.89% vs. 36.27%); the proportion of tumor, node, metastasis (TNM) stages Ⅲ–Ⅳ (69.44% vs. 44.12%); the proportion of recurrence risk stratification medium/high risk (91.67% vs. 68.63%); preablation stimulated thyroglobulin (psTg) level before treatment (1.65 (0.90, 1.87) μg/L vs. 1.32 (0.65, 1.66) μg/L); and lymph node short diameter in the non-ER group ((6.33±2.01) mm vs. (4.52±1.43) mm) were higher than those in the ER group, and the thyroid-stimulating hormone (TSH) level (59.10 (35.32, 118.33) mU/L vs. 65.33 (42.41, 120.33) mU/L), and iodine uptake rate before treatment ((5.63±1.50)% vs. (8.65±2.33)%) were lower than those in the ER group, with statistically significant differences (t=5.314, 5.837; χ2=6.829–8.257; Z=4.683, 6.861; all P<0.05). Multivariate Logistic regression analysis showed the following predictive factors of the unsatisfactory response to the first 131I treatment after DTC operation: the level of TSH before treatment, the proportion of extraglandular invasion, the proportion of TNM stages Ⅲ–Ⅳ, the proportion of middle/high risk of recurrence risk stratification, the level of psTg, the short diameter of lymph nodes, and the iodine uptake rate (OR=1.941–4.545, all P<0.01). The ROC curve analysis results showed that the critical value of the maximum Yodon index of the short diameter of lymph nodes displayed by SPECT/CT was 5.52 mm, and the AUC that predicted the unsatisfactory response to the first 131I treatment of DTC was 0.766 (95%CI: 0.687–0.834). The critical value corresponding to the maximum Yodon index of the iodine uptake rate was 7.47%, with an AUC of 0.749 (95%CI: 0.669–0.819), and the AUC of the combination of the two is 0.911 (95%CI: 0.850–0.953). The AUC predicted by the two methods for the first 131I treatment response of DTC was higher than that predicted by the two methods alone, and the difference was statistically significant (P<0.001). Conclusion The short diameter of lymph nodes of SPECT/CT imaging and the iodine uptake rate are considered as predictors of dissatisfaction with the first 131I treatment effect to DTC, and such predictors are of great importance in predicting the response of 131I treatment. Furthermore, the combination of the two methods has a better predictive value. -
表 1 138例分化型甲状腺癌患者首次131I治疗的反应结果及临床资料的单因素Logistic回归分析
Table 1. Results and clinical data univariate Logistic regression analysis of 138 patients with differentiated thyroid carcinoma treated with 131I for the first time
临床资料 疗效满意组(n=102) 非疗效满意组(n=36) 检验值 P值 性别 χ2=1.984 0.159 男(例,%) 25(24.51) 11(30.56) 女(例,%) 77(75.49) 25(69.44) 原发肿瘤长径(cm, )$ \bar x \pm {{s}} $ 1.41±0.30 1.52±0.35 t=−1.809 0.073 病理类型 χ2=0.030 0.861 乳头状癌(例,%) 93(91.18) 35(97.22) 滤泡状癌(例,%) 9(8.82) 1(2.78) 治疗前TSH水平[mU/L,M(Q1,Q3)] 65.33(42.41,120.33) 59.10(35.32,118.33) Z=6.861 <0.001 腺外浸润 χ2=8.257 0.004 有(例,%) 37(36.27) 23(63.89) 无(例,%) 65(63.73) 13(36.11) TNM分期 χ2=6.829 0.009 Ⅰ~Ⅱ(例,%) 57(55.88) 11(30.56) Ⅲ~Ⅳ(例,%) 45(44.12) 25(69.44) 复发风险分层 χ2=7.461 0.006 低风险(例,%) 32(31.37) 3(8.33) 中/高风险(例,%) 70(68.63) 33(91.67) 手术切除方式 χ2=1.422 0.233 全切(例,%) 68(66.67) 30(83.33) 近全切(例,%) 34(33.33) 6(16.67) psTg水平 [μg/L,M(Q1, Q3)] 1.32(0.65,1.66) 1.65(0.90,1.87) Z=4.683 <0.001 首次131I治疗剂量(GBq, )$ \bar x \pm {{s}} $ 5.35±1.43 5.88±0.61 t=1.888 0.061 淋巴结短径(mm, )$ \bar x \pm {{s}} $ 4.52±1.43 6.33±2.01 t=5.837 <0.001 碘摄取率(%, )$ \bar x \pm {{s}} $ 8.65±2.33 5.63±1.50 t=5.314 <0.001 注:TSH为促甲状腺激素;TNM为肿瘤、淋巴结、转移;psTg为治疗前刺激性甲状腺球蛋白 表 2 138例分化型甲状腺癌患者首次131I治疗疗效反应不满意预测因素的多因素Logistic回归分析
Table 2. Multivariate Logistic regression analysis of predictors of unsatisfactory response to 131I treatment for the first time in 138 patients with differentiated thyroid carcinoma
变量 回归系数 标准误 Wald值 OR值 95%CI P值 治疗前TSH水平 1.544 0.272 30.982 4.545 2.251~6.354 <0.001 腺外浸润占比 0.887 0.263 11.375 3.012 1.526~4.857 <0.001 TNM分期Ⅲ~Ⅳ期占比 0.785 0.270 8.453 2.192 1.322~3.560 <0.001 复发风险分层中/高风险 0.663 0.288 5.300 1.941 0.948~3.251 0.001 psTg水平 0.912 0.252 13.098 2.489 1.653~5.012 <0.001 淋巴结短径 1.314 0.257 26.141 3.721 2.013~6.217 <0.001 碘摄取率 1.135 0.298 14.506 3.511 1.858~5.624 <0.001 常量 −10.325 1.245 71.852 0.000 − − 注:−表示无此项数据。TSH为促甲状腺激素;TNM为肿瘤、淋巴结、转移;psTg为治疗前刺激性甲状腺球蛋白;CI为置信区间 表 3 SPECT/CT显像的淋巴结短径及碘摄取率对分化型甲状腺癌患者首次131I治疗反应疗效不满意的预测结果
Table 3. Predictive results of SPECT/CT lymph node short diameter and iodine uptake rate on non-excellent response response to the first 131I treatment in differentiated thyroid carcinoma patients
指标 AUC 95%CI P值 临界值 灵敏度(%) 特异度(%) 约登指数 淋巴结短径(mm) 0.766 0.687~0.834 <0.001 5.52 78.43 72.22 0.507 碘摄取率(%) 0.749 0.669~0.819 <0.001 7.47 64.71 88.89 0.536 淋巴结短径+碘摄取率 0.911 0.850~0.953 <0.001 − 99.02 83.33 0.823 注:−表示无此项数据。SPECT为单光子发射计算机体层摄影术;CT为计算机体层摄影术;AUC为曲线下面积;CI为置信区间 -
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