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甲状腺癌是内分泌系统最常见的恶性肿瘤,约占全身恶性肿瘤的1%,其发病率正在逐年上升[1]。甲状腺癌最常见的病理类型是DTC,其中约80%以上为甲状腺乳头状癌(papillary thyroid cancer,PTC),约15%以上为滤泡状癌。131I是治疗DTC的重要手段,随着131I的广泛应用,辐射安全问题日益受到关注。我国2002年辐射安全标准规定:131 I 治疗后,患者体内滞留活度降低至400 MBq(10.8 mCi)之前不得出院[2], 目前研究较多的是大剂量131I治疗后辐射剂量率的变化及所需住院隔离的时间,但对131I治疗后辐射剂量率的影响因素的研究较少,另外,近年来,131I治疗DTC的观念也在不断更新,对于无病灶患者更趋向于行小剂量131I清甲治疗[3-4],但目前尚缺乏小剂量131I清甲治疗的辐射剂量率的研究。本研究探讨PTC患者经过不同剂量131I治疗后的辐射剂量率的变化及影响因素,并预估患者所需住院隔离时间,为评估患者辐射风险及合理制定个性化防护指导提供理论依据。
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高剂量组和低剂量组患者在性别构成、年龄分布、病理T分期、病理N分期、尿碘、残甲法1和残甲法2上差异均无统计学意义(Z=−1.554~−0.100,均P>0.05),在131I剂量、治疗前TSH、治疗前Tg、治疗前TGAb、2 h摄碘率、6 h摄碘率、残甲法3、颈部摄碘灶上差异均有统计学意义(Z =−11.231~−3.165,均P<0.01)(表1)。
项目 高剂量组(n=63) 低剂量组(n=104) Z值 P值 性别 −0.909 0.419 男 14(22.2%) 29(27.9%) 女 49(77.8%) 75(72.1%) 年龄(岁) 36.06±12.89 38.23±11.41 −1.391 0.164 131I剂量(MBq) 5336.42±915.94 1547.60±406.84 −11.231 0.000 病理T分期 −1.753 0.080 Tx 3(4.8%) 13(12.5%) T1a/b 41(65.1%) 70(67.3%) T2 6(9.5%) 2(1.9%) T3 4(6.3%) 6(5.8%) T4a/b 9(14.3%) 13(12.5%) 病理N分期 −1.068 0.285 N0 7(11.1%) 10(9.6%) N1a 29(46.0%) 40(38.5%) N1b 27(42.9%) 54(51.9%) 治疗前TSH(μg/L) 62.6±20.26 78.79±25.41 −3.870 0.000 治疗前Tg(μg/L) 7.08(0.04~269.80) 0.85(0.04~16.40) −4.596 0.000 治疗前TGAb(KU/L) −3.165 0.002 阴性(0~115) 49(77.8%) 98(94.2%) 阳性(>115) 14(22.2%) 6(5.8%) 尿碘(μg/L) 30(20~500) 30(30~300) −0.100 0.921 2 h摄碘率(%) 2.90(0.60~10.30) 2.25(1.20~18.00) −3.396 0.001 6 h摄碘率(%) 2.40(0.50~16.60) 1.90(0.40~17.5) −3.363 0.001 24 h摄碘率(%) 1.50(0.1~26.8) − − − 24 h饮水量(mL) − 3554.33±1228.47 − − 48 h饮水量(mL) − 6384.62±1922.43 − − 残甲法1 −1.554 0.120 无残留 13(20.6%) 33(31.7%) 极少量残留 14(22.2%) 13(12.5%) 少量残留 25(39.7%) 54(51.9%) 部分残留 11(17.5%) 4(3.8%) 残甲法2 −0.242 0.809 无残留 11(17.5%) 17(16.3%) 极少量残留 13(20.6%) 13(12.3%) 少量残留 28(44.4%) 70(67.3%) 部分残留 11(17.5%) 4(3.8%) 残甲法3 −3.180 0.010 无残留 2(3.2%) 2(1.9%) 极少量残留 1(1.6%) 8(7.7%) 少量残留 48(76.2%) 91(87.5%) 部分残留 12(19.0%) 3(2.9%) 颈部摄碘灶 −4.338 0.000 无 46(73.0%) 100(96.2%) ≤3个 14(22.2%) 4(3.8%) >3个 3(4.8%) 0(0.0%) 24 h辐射剂量率(μSv/h) 70.62±34.45 11.27±5.13 −10.691 0.000 48 h辐射剂量率(μSv/h) 15.64(2.59~92.75) 2.03(0.47~16.40) −10.348 0.000 注:表中,TSH:促甲状腺激素;Tg:甲状腺球蛋白;TGAb:甲状腺球蛋白抗体。残甲法1:甲状腺静态显像法评估残留甲状腺;残甲法2:唾液腺动态显像法评估残留甲状腺;残甲法3:行131I治疗后全身显像法评估残留甲状腺;−:无此项数据 表 1 167例甲状腺乳头状癌患者的临床特点
Table 1. Clinical characteristics of 167 patients with papillary thyroid carcinoma
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高剂量组和低剂量组的辐射剂量率随时间推移迅速下降,高剂量组下降速率随时间推移减缓。两组患者的24 h和48 h的辐射剂量率差异有统计学意义(t=−13.581、−7.952,均P<0.001)(表2)。高剂量组服用131I后24、48、72 h体内放射性活度滞留量分别为941.6、272.8、192.4 MBq,低剂量组服用131I后24、48 h体内放射性活度滞留量分别为150.3、32.9 MBq。
24 h 48 h 72 h 96 h(n=34) 高剂量组(n=63) 70.62± 34.45 15.64
(2.59~92.75)9.27
(2.05~89.45)2.21
(0.62~77.38)低剂量组(n=104) 11.27±5.13 2.03
(0.47~16.40)− − t值 −13.581 −7.952 − − P值 <0.001 <0.001 − − 注:表中,−:无此项数据 表 2 不同时间点距离2组甲状腺乳头状癌患者1 m处的 辐射剂量率(μSv/h)
Table 2. Radiation dose rates (μSV/h) at different time points at one meter in two groups of papillary thyroid carcinoma patients
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将131I治疗后患者体内滞留131I活度为400 MBq时(相当于距离患者1 m处的剂量率约为30 μSv/h)的时间点定为出院时间。低剂量组治疗后24 h,仅1例患者未达到出院标准(24 h辐射剂量率为41.72 μSv/h))(表3),该患者为1例老年男性患者,超声提示其前列腺肿大,24 h饮水量仅为1500 mL,明显低于其他患者(平均3554 mL)。高剂量组治疗后48 h和72 h分别有19.0%(12/63)、9.5%(6/63)的患者未达到出院标准(表3),治疗后48 h未达标的12例中有10例相关检查均提示残留甲状腺较多,另外2例48 h辐射剂量率分别为32.27、32.95 μSv/h,已接近出院标准,而治疗后72 h未达标的6例患者相关检查均提示残留甲状腺较多。低剂量组和高剂量组的住院时间分别为(1.01±0.10)d和(2.22±0.77)d。
组别 例数 24 h 48 h 72 h 96 h 高剂量组 63 5(8.0) 51(81.0) 57(90.5) 62(98.4) 低剂量组 104 103(99.0) 104(100) − − 注:表中,−:无此项数据 表 3 两组甲状腺乳头状癌患者不同时间点出院达标率(例,%)
Table 3. Reach the discharge standard of two papillary thyroid carcinoma patients' groups at different time points
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将可能会影响辐射剂量率的因素包括性别、年龄、131I剂量、病理T分期(AJCC第7版)、病理N分期(AJCC第7版)、2 h摄碘率、6 h摄碘率、24 h吸碘率(高剂量组)、治疗前TSH、治疗前Tg、治疗前TGAb、残甲法1、残甲法2、残甲法3和颈部摄碘灶、24 h饮水量(低剂量组)作为自变量,高剂量组分别以24 h和48 h辐射剂量率作为因变量,低剂量组以24 h辐射剂量率作为因变量,采用多重线性回归分析辐射剂量率与各因素之间的关系。131I剂量和2 h摄碘率对高剂量组24 h辐射剂量率的影响有统计学意义(F=9.23,复相关系数R2=0.212,P<0.01)。高剂量组24 h辐射剂量率与131I剂量和2 h摄碘率呈正相关。性别、24 h摄碘率和残甲法3对高剂量组48 h辐射剂量率的影响有统计学意义(F=34.45,复相关系数R2=0.622,P<0.01)。高剂量组48 h辐射剂量率与性别呈负相关,与24 h摄碘率和残甲法3呈正相关,其中甲状腺的残留量对48 h辐射剂量率影响最大。131I剂量和24 h饮水量对低剂量组24 h辐射剂量率的影响有统计学意义(F=12.76,复相关系数R2=0.186,P<0.01)。低剂量组24 h辐射剂量率与131I剂量呈正相关,与24 h饮水量呈负相关(表4)。
组别 因变量 自变量 非标准化系数 标准化系数 t值 P值 B的95%可变区间 B 标准误 Beta 高剂量组(n=63) 24 h辐射剂量率 常量 −14.612 25.622 − −0.571 0.571 (−65.881~36.656) 2 h摄碘率 7.474 1.928 0.450 3.877 0.000 (3.617~11.332) 131I剂量 0.416 0.161 0.301 2.592 0.012 (0.095~0.737) 48 h辐射剂量率 常量 −9.625 9.216 − −1.044 0.301 (−28.073~88.823) 24 h摄碘率 1.548 0.264 0.586 5.868 0.000 (1.020~2.076) 残甲法3 9.036 3.126 0.289 2.891 0.005 (2.779~15.294) 性别 −7.729 3.377 −0.181 −2.289 0.026 (−14.489~969.000) 低剂量组(n=104) 24 h辐射剂量率 常量 8.213 2.204 − 3.727 0.000 (3.841~12.584) 131I剂量 0.170 0.041 0.364 4.090 0.000 (0.087~0.252) 24 h饮水量 −0.001 0.000 −0.272 −3.058 0.003 (−0.002~0.000) 注:表中,残甲法3:行131I治疗后全身显像法评估残留甲状腺;−:无此项数据 表 4 2组甲状腺乳头状癌患者辐射剂量率影响因素的多重线性回归分析
Table 4. Multiple linear regression analysis of the influencing factors of radiation dose rate in high dose and low dose groups of the papillary thyroid carcinoma patients
甲状腺乳头状癌患者术后首次131I治疗后辐射剂量率的影响因素及出院时间的探讨
Factors of radiation dose rates and hospitalization days for papillary thyroid cancer patients with after first 131I therapy
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摘要:
目的 探讨甲状腺乳头状癌(PTC)患者术后首次131I 治疗后影响辐射剂量率降低的相关因素,并预估其住院隔离时间。 方法 选取2015 年5月至 2018 年11月于南方医科大学珠江医院住院并首次行131I 治疗的 PTC 患者167 例,其中男性 43 例、女性 124 例,年龄(37.14±12.00)岁。将所有患者按治疗剂量分为高剂量组(63 例)和低剂量组(104 例),于治疗后24、48、72、96 h时测量距离患者 1 m处的辐射剂量率,将治疗后患者体内滞留131I 活度为 400 MBq时的时间点定为出院时间。采用多重线性回归方法分析影响辐射剂量率降低的相关因素。组间比较采用两独立样本非参数检验或两独立样本 t 检验。 结果 PTC 患者首次行131I 治疗后的辐射剂量率随时间推移迅速下降,高剂量组治疗后的 24、48 h 辐射剂量率[(70.62±34.45)、15.64 μSv/h]明显高于低剂量组[(11.27±5.13)、2.03 μSv/h],且差异均有统计学意义(t=−13.581、−7.952,均 P <0.01)。81.0%(51/63)和 90.5%(57/63)的高剂量组患者分别可在治疗48 h 和 72 h 后出院,99%(103/104)的低剂量组患者可在治疗24 h 后出院。多重线性回归分析显示,131I剂量和2 h摄碘率对高剂量组24 h辐射剂量率的影响有统计学意义(F=9.23,复相关系数R2=0.212,P<0.01),高剂量组 24 h 辐射剂量率与 2 h 摄碘率和131I 剂量呈正相关;性别、24 h摄碘率和残甲法3对高剂量组48 h辐射剂量率的影响有统计学意义(F=34.45,复相关系数R2=0.622,P<0.01),48 h 辐射剂量率与 24 h 摄碘率和残留甲状腺体积呈正相关,与性别呈负相关;131I剂量和24 h饮水量对低剂量组24 h辐射剂量率的影响有统计学意义(F=12.76,复相关系数R2=0.186,P<0.01),低剂量组 24 h 辐射剂量率与131I剂量呈正相关,与24 h饮水量呈负相关。 结论 PTC 术后患者首次131I 治疗24 h后,影响其辐射剂量率降低的主要因素是服用131I 的剂量,而 48 h 后的主要影响因素是 24 h 甲状腺摄碘率、残留甲状腺体积和性别。低剂量组和高剂量组平均住院时间分别为1 d和 2 d左右。 Abstract:Objective To explore the related factors affecting the reduction of radiation dose rate and to estimate the hospitalization days in papillary thyroid cancer (PTC) patients with postoperative after first 131I therapy. Methods A total of 167 patients with PTC were hospitalized and treated with iodine-131 from May 2015 to November 2018 at Zhujiang Hospital, Southern Medical University. The patients were divided into the high-dose group (63 cases) and the low dose-group (104 cases). The radiation dose rates of the two groups of patients at different time points were measured at a distance of 1 m, the required hospitalization isolation time was analyzed, and the factors related to the reduction in radiation dose rate were analyzed by using multiple linear regression method. Two independent samples nonparametric test and t-test were used to compare the differences between groups. Results After iodine-131 treatment for the first time, the radiation dose rate of the patients with PTC decreased exponentially with time, and the radiation dose rates of the high-dose group[(70.62± 34.45), 15.64 μSv/h] at 24 h and 48 h after iodine-131 treatment were significantly higher than those of the low-dose group [(11.27±5.13), 2.03 μSv/h] (t=−13.581, −7.952, both P < 0.01). Approximately 81.0% (51/63) and 90.5% (57/63) of the high-dose group were discharged after iodine-131 treatment for 48 h and 72 h, respectively. By contrast, 99% (103/104) of the low-dose group was discharged after iodine-131 treatment for 24 h. According to multiple linear regression analysis, the effects of iodine-131 dose, iodine uptake rate at 2 h on radiation dose rate at 24 h in the high dose group were statistically significant (F = 9.23, complex correlation coefficient R2 = 0.212, P < 0.01), and both iodine-131 dose and iodine uptake rate at 2 h had positive correlation with 24 h radiation dose rate. The effects of gender, iodine uptake rate at 24 h and residual thyroid volume (method 3) on radiation dose rate at 48 h in the high-dose group were statistically significant (F=34.45, complex correlation coefficient R2 = 0.622, P < 0.01), moreover the radiation dose rate at 48 h was positively correlated with iodine uptake rate at 24 h and residual thyroid volume, and negatively correlated with gender. The effects of iodine-131 dose and drinking water amount at 24 h on the radiation dose rate at 24 h in the low-dose group were statistically significant (F=12.76, complex correlation coefficient R2=0.186, P < 0.01), furthermore the radiation dose rate at 24 h in the low-dose group was positively correlated with iodine-131 dose, and negatively correlated with drinking water amount at 24 h. Conclusions After the first iodine-131 treatment for 24 h, the main factors influencing the reduction in the radiation dose rate of patients with PTC were the dose of iodine-131. The main factors influencing the reduction in radiation dose rate after 48 h were the iodine uptake rate of the thyroid at 24 h, the volume of the residual thyroid gland, and the gender of the patient. The mean hospitalization time in low dose group and high dose group was about 1 day and 2 days respectively. -
表 1 167例甲状腺乳头状癌患者的临床特点
Table 1. Clinical characteristics of 167 patients with papillary thyroid carcinoma
项目 高剂量组(n=63) 低剂量组(n=104) Z值 P值 性别 −0.909 0.419 男 14(22.2%) 29(27.9%) 女 49(77.8%) 75(72.1%) 年龄(岁) 36.06±12.89 38.23±11.41 −1.391 0.164 131I剂量(MBq) 5336.42±915.94 1547.60±406.84 −11.231 0.000 病理T分期 −1.753 0.080 Tx 3(4.8%) 13(12.5%) T1a/b 41(65.1%) 70(67.3%) T2 6(9.5%) 2(1.9%) T3 4(6.3%) 6(5.8%) T4a/b 9(14.3%) 13(12.5%) 病理N分期 −1.068 0.285 N0 7(11.1%) 10(9.6%) N1a 29(46.0%) 40(38.5%) N1b 27(42.9%) 54(51.9%) 治疗前TSH(μg/L) 62.6±20.26 78.79±25.41 −3.870 0.000 治疗前Tg(μg/L) 7.08(0.04~269.80) 0.85(0.04~16.40) −4.596 0.000 治疗前TGAb(KU/L) −3.165 0.002 阴性(0~115) 49(77.8%) 98(94.2%) 阳性(>115) 14(22.2%) 6(5.8%) 尿碘(μg/L) 30(20~500) 30(30~300) −0.100 0.921 2 h摄碘率(%) 2.90(0.60~10.30) 2.25(1.20~18.00) −3.396 0.001 6 h摄碘率(%) 2.40(0.50~16.60) 1.90(0.40~17.5) −3.363 0.001 24 h摄碘率(%) 1.50(0.1~26.8) − − − 24 h饮水量(mL) − 3554.33±1228.47 − − 48 h饮水量(mL) − 6384.62±1922.43 − − 残甲法1 −1.554 0.120 无残留 13(20.6%) 33(31.7%) 极少量残留 14(22.2%) 13(12.5%) 少量残留 25(39.7%) 54(51.9%) 部分残留 11(17.5%) 4(3.8%) 残甲法2 −0.242 0.809 无残留 11(17.5%) 17(16.3%) 极少量残留 13(20.6%) 13(12.3%) 少量残留 28(44.4%) 70(67.3%) 部分残留 11(17.5%) 4(3.8%) 残甲法3 −3.180 0.010 无残留 2(3.2%) 2(1.9%) 极少量残留 1(1.6%) 8(7.7%) 少量残留 48(76.2%) 91(87.5%) 部分残留 12(19.0%) 3(2.9%) 颈部摄碘灶 −4.338 0.000 无 46(73.0%) 100(96.2%) ≤3个 14(22.2%) 4(3.8%) >3个 3(4.8%) 0(0.0%) 24 h辐射剂量率(μSv/h) 70.62±34.45 11.27±5.13 −10.691 0.000 48 h辐射剂量率(μSv/h) 15.64(2.59~92.75) 2.03(0.47~16.40) −10.348 0.000 注:表中,TSH:促甲状腺激素;Tg:甲状腺球蛋白;TGAb:甲状腺球蛋白抗体。残甲法1:甲状腺静态显像法评估残留甲状腺;残甲法2:唾液腺动态显像法评估残留甲状腺;残甲法3:行131I治疗后全身显像法评估残留甲状腺;−:无此项数据 表 2 不同时间点距离2组甲状腺乳头状癌患者1 m处的 辐射剂量率(μSv/h)
Table 2. Radiation dose rates (μSV/h) at different time points at one meter in two groups of papillary thyroid carcinoma patients
24 h 48 h 72 h 96 h(n=34) 高剂量组(n=63) 70.62± 34.45 15.64
(2.59~92.75)9.27
(2.05~89.45)2.21
(0.62~77.38)低剂量组(n=104) 11.27±5.13 2.03
(0.47~16.40)− − t值 −13.581 −7.952 − − P值 <0.001 <0.001 − − 注:表中,−:无此项数据 表 3 两组甲状腺乳头状癌患者不同时间点出院达标率(例,%)
Table 3. Reach the discharge standard of two papillary thyroid carcinoma patients' groups at different time points
组别 例数 24 h 48 h 72 h 96 h 高剂量组 63 5(8.0) 51(81.0) 57(90.5) 62(98.4) 低剂量组 104 103(99.0) 104(100) − − 注:表中,−:无此项数据 表 4 2组甲状腺乳头状癌患者辐射剂量率影响因素的多重线性回归分析
Table 4. Multiple linear regression analysis of the influencing factors of radiation dose rate in high dose and low dose groups of the papillary thyroid carcinoma patients
组别 因变量 自变量 非标准化系数 标准化系数 t值 P值 B的95%可变区间 B 标准误 Beta 高剂量组(n=63) 24 h辐射剂量率 常量 −14.612 25.622 − −0.571 0.571 (−65.881~36.656) 2 h摄碘率 7.474 1.928 0.450 3.877 0.000 (3.617~11.332) 131I剂量 0.416 0.161 0.301 2.592 0.012 (0.095~0.737) 48 h辐射剂量率 常量 −9.625 9.216 − −1.044 0.301 (−28.073~88.823) 24 h摄碘率 1.548 0.264 0.586 5.868 0.000 (1.020~2.076) 残甲法3 9.036 3.126 0.289 2.891 0.005 (2.779~15.294) 性别 −7.729 3.377 −0.181 −2.289 0.026 (−14.489~969.000) 低剂量组(n=104) 24 h辐射剂量率 常量 8.213 2.204 − 3.727 0.000 (3.841~12.584) 131I剂量 0.170 0.041 0.364 4.090 0.000 (0.087~0.252) 24 h饮水量 −0.001 0.000 −0.272 −3.058 0.003 (−0.002~0.000) 注:表中,残甲法3:行131I治疗后全身显像法评估残留甲状腺;−:无此项数据 -
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