CalliSpheres可载药微球经导管肝动脉化疗栓塞序贯射频消融治疗原发性肝癌患者疗效研究.pdf

基 金 项 目:山 东 省 自 然 科 学 基 金 资 助 项 目(编 号:ZR2019MH084)作者单位:257091 山东省东营市人民医院肝胆外科(刘公攀,丁志刚,任明,郭兴军,邵存华,卢建树);山东中医药大学第二附属医院检验科(陈涛)第一作者:刘公攀,男,45 岁,医学硕士,主治医师。E-mail:通讯作者:邵存华,E-mail:shaocunhua 肝癌CalliSpheres 可载药微球经导管肝动脉化疗栓塞序贯射频消融治疗原发性肝癌患者疗效研究刘公攀,陈 涛,丁志刚,任 明,郭兴军,邵存华,卢建树【摘要】目的 研究在经导管肝动脉化疗栓塞(TACE)术时应用 CalliSpheres 可载药微球化疗序贯射频消融(RFA)治疗原发性肝癌(PLC)患者的疗效。方法 2019 年1 月 2021 年1 月我院收治的 PLC 患者79 例,被分为两组,43 例观察组采用 CalliSpheres 可载药微球 TACE 序贯 RFA 治疗,36 对照组采用常规 TACE 序贯 RFA 治疗。根据实体瘤疗效考核标准评估短期疗效,采用电化学发光分析仪检测血清甲胎蛋白(AFP)和人热休克蛋白 90(HSP90)。随访 2 年,记录两组生存情况。结果 在治疗后 1 m 末,观察组肿瘤晚期缓解、部分缓解、疾病稳定和疾病控制率分别为 23.3%、46.5%、16.3%和 86.1%,对照组分别为 11.1%、36.1%、19.4%和 66.7%,其疾病控制率差异显著(P0.05);在治疗后 3 m,观察组血清 AFP 和 HSP90 水平分别为(87.514.5)g/L 和(126.113.3)ng/mL,均显著低于对照组【分别为(164.617.2)g/L 和(150.819.7)ng/mL,P0.05);观察组和对照组 1 a 生存率分别为 83.7%和 72.2%,差异无统计学意义(P0.05),而 2 a 生存率分别为69.8%和47.2%,差异有统计学意义(P0.05)。结论 采用 CalliSpheres 可载药微球 TACE 序贯 RFA 治疗 PLC 患者近期疗效显著,可有效提高患者近期生存率,值得进一步探究。【关键词】原发性肝癌;CalliSpheres 可载药微球;肝动脉化疗栓塞;射频消融;治疗 DOI:10.3969/j.issn.1672-5069.2023.06.028Efficacy of transcatheter arterial chemoembolization with CalliSpheres drug-loaded microspheres followed byradiofrequency ablation in the treatment of patients with primary liver cancer Liu Gongpan,Chen Tao,Ding Zhigang,et al.Department of Hepatobiliary Surgery,Peoples Hospital,Dongying 257091,Shandong Province,China【Abstract】ObjectiveThe aim of this study was to investigate the efficacy of transcatheter arterial chemoembolization(TACE)with CalliSpheres drug-loaded microspheres followed by radiofrequency ablation(RFA)in the treatment of patients withprimary liver cancer(PLC).Methods 79 patients with PLC were enrolled in our hospital between January 2019 and January2021,and were divided into observation(n=43)and control group(n=36),receiving TACE with CalliSpheres drug-loadedmicrospheres followed by RFA,or the routine TACE followed by RFA.All patients were followed-up for two years.The diseasecontrol rate in the two groups after treatment was evaluated according to the Response Evaluation Criteria in Solid Tumors.Serumalpha-fetoprotein(AFP)and human heat shock protein 90(HSP90)levels were detected by electrochemiluminescenceanalyzer.Results At the end of one month after treatment,the complete remission,partial remission,stable disease and the totaldisease control rate in the observation group were 23.3%,46.5%,16.3%and 86.1%,while they were 11.1%,36.1%,19.4%and 66.7%in the control,with the latter significantly different(P0.05)between the two groups;at the end of threemonths after treatment,serum AFP and HSP90 levels in the observation group were(87.514.5)g/L and(126.113.3)ng/mL,both significantly lower than(164.617.2)g/L and(150.819.7)ng/mL,respectively,P0.05);the one-year survival rates in the observation and control groups were 83.7%and 72.2%,not significantly different(P0.05),while the two-year survival rates were 69.8%and 47.2%,significantly different(P0.05)。患者及其家属签署知情同意书,本研究获得我院医学伦理委员会批准。1.2 治疗方法 在对照组,常规进行 TACE 序贯 RFA治 疗,在 观 察 组,在 行 TACE 治 疗 时,使 用CalliSpheres 可载药微球载药栓塞,序贯 RFA 治疗。常规消毒,采用改良的 Seldinger 技术经股动脉入路穿刺,置入 5F 鞘,在 X 线透视下将 5F RH 导管插入腹腔干动脉,造影,明确肿瘤供血动脉。然后,向肿瘤靶血管插入 2.7 F 微导管。经微导管注入碘化油(烟台鲁银药业有限公司,国药准字 H37022398)1030 mL,栓塞肿瘤末端血管,再注入表柔比星(浙江海正药业股份有限公司,国药准字 H19990279)50mg,最后注射明胶海绵颗粒以进一步栓塞,直至肿瘤血管血流被中断,结束栓塞;取 CalliSpheres 可载药微球(苏州恒瑞迦俐生生物医药科技有限公司),注入表柔比星 50 mg,与对比剂充分混匀,选择脉冲式注射栓塞,直至肿瘤血管血流被中断,结束栓塞。在TACE 术后 4 周行 RFA 治疗,使用美国 RITA 1500型 RFA 肿瘤治疗仪,参数:发射频率 400 kHz,功率1 250 w。首先,行腹部 CT 增强扫描,以确定肿瘤位置。患者采取平卧位,进行全身麻醉。在 CT 扫描引导下,选择穿刺点,确定进针的角度和深度,以金属颗粒进行标记,并再次进行 CT 扫描,确定穿刺点。使用多极 RFA 针,经皮肤穿刺至肿瘤边缘,并依次开展射频电极。针对肿瘤直径5 cm 的病灶,采用多点和多层面消融治疗,尽量完全消融瘤体。单次消融点位5 个,各点位消融15 min。于消融完成后,进行针道消融。在治疗结束后,进行护肝、止痛等处理。1.3 疗效评估 在治疗后一个月,对全部患者进行影像学检查。参考实体瘤疗效标准评估疗效,包括完全缓解(complete remission,CR)、部分缓解(partialremission,PR)、疾病稳定(stable disease,SD)和疾病进展(progressive disease,PD)。疾病控制率=(CR+PR+SD)/总例数100%1.4 血清指标检测 采用全自动生化分析仪检测血生化指标(北京普朗新技术有限公司);采用全自动凝血测试仪检测凝血酶原时间,自动给出国际标准化比值(international normalized ratio,INR,江苏天瑞精准医疗科技有限公司);采用电化学发光分析仪检测血清甲胎蛋白(alpha fetoprotein,AFP)、人热休克蛋白 90(heat shock protein 90 alpha,HSP90)、糖类抗原(carbohydrate antigen,CA)125 和 CA199 水平罗氏诊断产品(上海)有限公司。1.5 生存情况 采用门诊随访或电话随访的形式,随访 2 年,以随访结束或患者死亡为随访截止时间,计算生存率。1.6 统计学处理应用 IBM SPSS Statistics 24.0 统计学软件分析数据。计量资料均满足正态分布,以(xs)表示,采用 t 检验;计数资料以(%)表示,采用x2检验,P0.05 为差异有统计学意义。2 结果2.1 两组短期疗效比较 在治疗后一个月复查,观察088实用肝脏病杂志 2023 年 11 月第 26 卷第 6 期 J Prac Hepatol,November.2023.Vol.26 No.6组疾病控制率显著高于对照组,差异有统计学意义(P0.05,表 1)。2.2 两组血清肿瘤标志物水平比较在治疗后 3 m末,观察组血清 AFP 和 HSP90 水平显著低于对照组,差异有统计学意义(P0.05,表3)。表 1 两组疗效n(%)比较例数CRPRSDPD疾病控制观察组4310(23.3)20(46.5)7(16.3)6(14.0)37(86.1)对照组364(11.1)13(36.1)7(19.4)12(33.3)24(66.7)与对照组比,P0.05表 2 两组血清肿瘤标志物水平(xs)比较例数AFP(g/L)HSP90(ng/mL)CA125(U/mL)CA199(U/mL)观察组治疗前43424.173.0307.539.172.214.673.513.9治疗后4387.514.5126.113.325.76.0137.16.58对照组治疗前36418.369.6311.239.472.914.373.213.4治疗后36164.617.2150.819.727.37.8435.98.02 与对照组比,P0.05),而 2 a 生存率分别为69.8%和 47.2%,差异有统计学意义(P5 cm 肝细胞癌的前瞻性研究.中华消化外科杂志,2020,19(2):145-155.12 Peng N,Mao L,Tao Y,et al.Callispheres drug-eluting beadstransarterial chemoembolization might be an efficient and safetydown-staging therapy in unresectable liver cancer patients.World JSurg Oncol,2022,20(1):254-262.13 王婵,沈长清,吴晓琼,等.表柔比星药物洗脱微球肝动脉化疗栓塞术治疗不可手术切除的原发性肝癌患者临床疗效和安全性分析.实用肝脏病杂志,2022,25(2):259-262.14 Peng Z,Cao G,Hou Q,et al.The comprehensive analysis of effi-cacy and safety of CalliSpheres drug-eluting beads transarterialchemoembolization in 367 liver cancer patients:a multiple-center,cohort study.Oncol Res,2020,28(3):249-271.15 吕然,刘琛志.CalliSpheres 载药微球 TACE 序贯微波消融治疗单发直径5cm 原发性老年肝癌的临床研究.中华肿瘤防治杂志,2022,29(15):1136-1142.16 Duan X,Zhao G,Han X,et al.Arsenic trioxide-loaded CalliSph-eres:In vitro study of drug release and antitumor activity,and in vi-vo study of pharmacokinetics,treatment efficacy and safety in livercancer.Oncol Rep,2021,46(1):124-136.17 张笑时,吕少诚,潘飞,等.甲胎蛋白水平与肿瘤总体积比值对肝癌肝移植患者预后的影响.中华肝胆外科杂志,2021,27(3):215-217.18 Wei W,Liu M,Ning S,et al.Diagnostic value of plasma HSP90levels for detection of hepatocellular carcinoma.BMC Cancer,2020,20(1):6-14.19 Qin C,Gao Y,Li J,et al.Predictive effects of preoperative serumCA125 and AFP levels on post-hepatectomy survival in patientswith hepatitis B-related hepatocellular carcinoma.Oncol Lett,2021,21(6):487-499.20 Zhang J,Feng GA,Li Y,et al.Drug-eluting bead transarterialchemoembolizationwithmedium-sizedversussmall-sizedCalliSpheres microspheres in unresectable primary liver cancer.Asia Pac J Clin Oncol,2022,18(4):388-393.(收稿:2023-02-17)(本文编辑:陈宗炳)288实用肝脏病杂志 2023 年 11 月第 26 卷第 6 期 J Prac Hepatol,November.2023.Vol.26 No.6