^(177)Lu-DOTATATE治疗神经内分泌肿瘤的安全性和有效性  

Safety and efficacy of ^(177)Lu-DOTATATE for neuroendocrine neoplasms

作　　者：何丽萌 刘楠 邓颖[1] 李红梅 陈跃 张伟[1] He Limeng;Liu Nan;Deng Ying;Li Hongmei;Chen Yue;Zhang Wei(Department of Nuclear Medicine,Sichuan Provincial Academy of Medical Sciences-Sichuan Provincial People′s Hospital(Affiliated Hospital of the University of Electronic Science and Technology),Chengdu 610072,China;Department of Nuclear Medicine,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province,the Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)

机构地区：[1]四川省医学科学院·四川省人民医院(电子科技大学附属医院)核医学科,成都610072 [2]西南医科大学附属医院核医学科、核医学与分子影像四川省重点实验室,泸州646000

出　　处：《中华核医学与分子影像杂志》2023年第11期655-659,共5页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金(81960320);四川省自然科学基金(23NSFSC1548)。

摘　　要：目的探索^(177)Lu-1, 4, 7, 10-四氮杂环十二烷-1, 4, 7, 10-四乙酸-D-苯丙氨酸1-酪氨酸3-苏氨酸8-奥曲肽(DOTATATE)用于神经内分泌肿瘤(NEN)患者的疗效和不良反应。方法回顾性纳入2019年10月至2021年6月间在西南医科大学附属医院接受^(177)Lu-DOTATATE治疗的36例转移性NEN患者[男26例、女10例, 年龄(43.5±12.9)岁]。采用不良事件通用术语标准5.0版进行毒性评估。根据实体瘤疗效评价标准(RECIST)1.1版确定疾病进展和肿瘤反应。采用Cox比例风险模型分析无进展生存(PFS)和总生存(OS)的预后因素。结果 36例患者的中位随访时间为19.8个月, 中位PFS为24.0个月, 未达到中位OS。WHO Ⅲ级[PFS:风险比(HR)=3.59, 95%CI: 1.10~11.73, P=0.025;OS:HR=7.85, 95%CI:1.50~41.10, P=0.004]、^(18)F-FDG PET阳性(PFS:HR=3.05, 95%CI:1.04~8.93, P=0.033;OS:HR=5.90, 95%CI:1.04~33.49, P=0.025)以及肽受体放射性核素治疗(PRRT)前接受了全身化疗(PFS:HR=2.79, 95%CI:1.01~7.73, P=0.039;OS:HR=5.56, 95%CI:1.01~30.57, P=0.026)是PFS和OS的预后因素。一过性不良反应包括疲劳(27.8%, 10/36)和恶心(5.6%, 2/36), 最常见的实验室毒性是淋巴细胞减少(11.1%, 4/36), 其次是轻度肾毒性(8.3%, 3/36)和轻度肝损伤(5.6%, 2/36)。结论 ^(177)Lu-DOTATATE PRRT是有效且患者耐受性良好的NEN治疗方法。WHO Ⅲ级、^(18)F-FDG PET阳性及PRRT前接受过全身化疗的NEN患者的PFS和OS较短。Objective To explore the efficacy and adverse effects of ^(177)Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotide(DOTATATE)in patients with neuroendocrine neoplasms(NEN).Methods From 2019 to June 2021,36 patients(26 males,10 females;age(43.5±12.9)years)with metastatic NEN who were treated with ^(177)Lu-DOTATATE in the Affiliated Hospital of Southwest Medical University were retrospectively analyzed.Toxicities were assessed by using the common terminology criteria for adverse events(CTCAE)version 5.0.Disease progression and tumor response were determined according to the response evaluation criteria in solid tumors(RECIST)version 1.1.Prognostic factors for progression-free survival(PFS)and overall survival(OS)were analyzed by Cox proportional-hazards model.Results Of 36 patients,the median follow-up time was 19.8 months,the median PFS was 24 months,and the median OS was not reached.The WHO gradeⅢ(hazard ratio(HR)=3.59,95%CI:1.10-11.73,P=0.025;OS:HR=7.85,95%CI:1.50-41.10,P=0.004),^(18)F-FDG positive(PFS:HR=3.05,95%CI:1.04-8.93,P=0.033;OS:HR=5.90,95%CI:1.04-33.49,P=0.025),and received systemic chemotherapy before peptide receptor radionuclide therapy(PRRT)(PFS:HR=2.79,95%CI:1.01-7.73,P=0.039;OS:HR=5.56,95%CI:1.01-30.57,P=0.026)were prognostic factors for PFS and OS.Transient side effects included fatigue(27.8%,10/36),nausea(5.6%,2/36),and the most common laboratory toxicities were lymphocytopenia(11.1%,4/36),followed by mild renal toxicity(8.3%,3/36)and mild liver injury(5.6%,2/36).Conclusions PRRT with ^(177)Lu-DOTATATE is an effective and well-tolerated treatment in patients with NEN.PFS and OS are shorter in patients who are WHO gradeⅢNEN,^(18)F-FDG positive,and received systemic chemotherapy before PRRT.

关 键 词：神经内分泌瘤 受体 肽 有机金属化合物 同位素标记 镥 

分 类 号：R739.4[医药卫生—肿瘤]