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125I腔内照射联合仑伐替尼治疗进展期肝外胆管癌的效果和安全性分析
DOI: 10.3969/j.issn.1001-5256.2023.10.019
伦理学声明：本研究方案于2023年3月6日经郑州大学第一附属医院伦理委员会审批通过，批号：2023－KY－0064，符合《赫尔辛基宣言》，患者均签署知情同意书。
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：朱兴书负责收集数据，资料分析，撰写及修改论文；陈鹏飞、张萌帆负责修改论文；李方正、陈金威参与收集数据与资料分析；任建庄、段旭华、张文广拟定课题设计，写作思路，指导撰写文章；韩新巍负责写作思路并最后定稿。
Efficacy and safety of 125I intraluminal irradiation combined with lenvatinib in treatment of progressive extrahepatic cholangiocarcinoma
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摘要:
目的 探讨125I腔内照射联合仑伐替尼治疗进展期肝外胆管癌的有效性和安全性。 方法 回顾性纳入2018年1月—2021年11月于郑州大学第一附属医院介入科就诊的进展期肝外胆管癌患者25例。根据治疗方式分为两组，125I腔内照射联合仑伐替尼组患者13例（联合组）和单纯125I腔内照射组12例（对照组）。记录技术成功率、肝功能变化、支架通畅情况、生存期和不良事件的发生情况。正态分布的计量资料两组间比较采用成组t检验，偏态分布的计量资料两组比较采用Wilcoxon秩和检验，计数资料组间比较采用Fisher确切概率法。采用Kaplan－Meier和Log－rank检验评估生存期和支架通畅情况。 结果 两组所有患者均成功植入胆道支架和125I粒子，技术成功率100%。治疗1个月后，两组患者血清TBil、DBil、ALT和AST显著改善，与治疗前比较差异均有统计学意义（P值均<0.05）。对照组和联合组的中位支架通畅期分别为7.0和9.5个月，差异有统计学意义（P=0.022），中位生存期分别为11.5和15.6个月，差异有统计学意义（P=0.008）。治疗过程中联合组未出现不可耐受的不良事件。 结论 125I腔内照射联合仑伐替尼对比单纯125I腔内照射治疗进展期肝外胆管癌具有更好的疗效，是一种安全、有效的治疗方案。 Abstract:Objective To investigate the efficacy and safety of 125I intraluminal irradiation combined with lenvatinib in the treatment of progressive extrahepatic cholangiocarcinoma. Methods A retrospective analysis was performed for 25 patients with progressive extrahepatic cholangiocarcinoma who attended Department of Interventional Radiology， The First Affiliated Hospital of Zhengzhou University， from January 2018 to November 2021， and according to the treatment modality， they were divided into combination group with 13 patients （125I intraluminal irradiation combined with lenvatinib） and control group （125I intraluminal irradiation alone）. The two groups were compared in terms of technical success rates， changes in liver function， stent patency， survival time， and incidence rates of adverse events. The independent－samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank－sum test was used for comparison of continuous data with skewed distribution between two groups； the Fisher’s exact test was used for comparison of categorical data between groups. The Kaplan－Meier method and the log－rank test were used to evaluate survival time and stent patency. Results All patients had successful implantation of biliary stents and 125I particles， with a technical success rate of 100%. After 1 month of treatment， both groups had significant improvements in the serum levels of total bilirubin， direct bilirubin， alanine aminotransferase， and aspartate aminotransferase （all P<0.05）. There were significant differences between the control group and the combination group in the duration of stent patency （7.0 months vs 9.5 months， P=0.022） and median survival time （11.5 months vs 15.6 months， P=0.008）. There were no intolerable adverse events in the combination group during treatment. Conclusion Compared with 125I intraluminal irradiation alone， 125I intraluminal irradiation combined with lenvatinib has better efficacy and is a safe and effective treatment regimen for progressive extrahepatic cholangiocarcinoma. -
Key words:
- Cholangiocarcinoma /
- Iodine Radioisotopes /
- Lenvatinib /
- Radiology， Interventional
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图 1 49岁男性胆管恶性肿瘤伴梗阻性黄疸患者活检和介入治疗过程
注： a，透视下造影可见胆总管中下段严重狭窄，对比剂通过困难（箭头）；b，透视下活检钳张开（箭头）；c， 透视下活检钳夹取病理组织（箭头）；d，引入8.5F内外引流管，远端成袢于十二指肠，行胆汁引流；e，病理结果证实为胆管癌后，行胆道支架（箭头）植入；f，自制粒子链（箭头）经胆道引流管进入病灶内，完全覆盖病灶；g、h、i粒子链置入3天内单光子发射计算机断层成像图示冠状位（g）、矢状位（h）、横轴位（i）放射剂量分布。
Figure 1. Biopsy and interventional procedure in a 49－year－old male patient with biliary malignancy with obstructive jaundice
表 1 两组患者基线资料对比
Table 1. Comparison of information between the two groups
指标 联合组（n=13） 对照组（n=12） P值 性别（例） >0.05 男 6 5 女 7 7 年龄（例） 0.378 ≥65岁 11 8 <65岁 2 4 Child－Pugh分级（例） 0.434 A级 5 7 B级 8 5 类型（例） 0.238 远端胆管癌 9 5 肝门部胆管癌 4 7 ECOG评分（例） 0.695 0分 8 6 1分 5 6 
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表 2 两组间治疗后1个月肝功能指标对比
Table 2. Comparison of liver function indicators between the two groups at 1 month after treatment
组别 例数 TBil（μmol/L） DBil（μmol/L） ALT（U/L） AST（U/L） 联合组 13 17.13±10.56 11.96±8.20 24.00（19.50～40.00） 32.38±9.36 对照组 12 26.15±11.51 16.52±10.43 34.50（24.50～49.75） 35.25±11.93 统计值 t=－2.044 t=－1.221 Z=－1.279 t=－0.671 P值 0.053 0.234 0.201 0.509
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表 3 两组患者治疗前、治疗后1个月肝功能指标组内比较
Table 3. Comparison of liver function indicators before and after 1month of treatment in two groups
组别 例数 TBil（μmol/L） DBil（μmol/L） ALT（U/L） AST（U/L） 联合组 13 术前 208.49±114.88 170.77±111.77 122.0（98.5～194.5） 132.0（96.5～193.5） 术后 17.13±10.56 11.96±8.20 24.0（19.5～40.0） 30.0（27.0～38.0） 统计值 t=6.076 t=5.188 Z=－4.026 Z=－4.338 P值 <0.01 <0.01 <0.01 <0.01 对照组 12 术前 206.54±95.76 173.54±83.70 173.50±66.03 162.58±51.87 术后 26.15±11.51 16.52±10.43 36.67±15.92 35.25±11.93 t值 6.816 6.747 6.977 7.902 P值 <0.01 <0.01 <0.01 <0.01
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表 4 联合组不良事件的发生情况
Table 4. Occurrence of adverse events in the combined group
不良事件 1～2级［例（%）］ 3～4级［例（%）］ 不良事件总发生率（%） 高血压 5（38.5） 1（7.7） 46.2 乏力 6（46.2） 0（0.0） 46.2 AST或ALT升高 2（15.4） 0（0.0） 15.4 皮疹 1（7.7） 0（0.0） 7.7 腹痛 1（7.7） 1（7.7） 7.7 腹泻 2（15.4） 0（0.0） 15.4 食欲减退 4（30.8） 0（0.0） 30.8 恶心 4（30.8） 0（0.0） 30.8 血小板下降 1（7.7） 0（0.0） 7.7 蛋白尿 1（7.7） 1（7.7） 15.4 手足综合征 3（23.1） 0（0.0） 23.1
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