Peptide Receptor Radionuclide Therapy of Late-Stage Neuroendocrine Tumor Patients with Multiple Cycles of 177Lu-DOTA-EB-TATE
Peptide Receptor Radionuclide Therapy of Late-Stage Neuroendocrine Tumor Patients with Multiple Cycles of 177Lu-DOTA-EB-TATE
复制标题
177Lu-DOTA-EB-TATE多周期肽受体放射性核素治疗晚期神经内分泌肿瘤患者
DOI：
10.2967/jnumed.120.248658
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发表时间：
2021-03-01
影响因子：
9.3
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
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作者：
Liu, Qingxing;Zang, Jie;Chen, Xiaoyuan
本研究旨在评价多周期递增剂量177Lu-DOTA-Evans Blue(EB)-Tate多肽受体放射性核素治疗神经内分泌肿瘤的安全性和有效性。方法：将32例Net患者随机分为3组，分别给予递增剂量治疗。A组为1.17±0.09GBq/周期，B组为1.89±0.53GBq/周期，C组为3.97±0.84GBq/周期。治疗计划长达3个周期。根据国家癌症研究所不良事件通用术语标准(CTCAE)5.0版对与治疗相关的不良事件进行分级。根据欧洲癌症研究和治疗组织的标准和修订的PERCIST对治疗反应进行评估。结果：PRRT给药耐受性良好，无危及生命的不良反应(CTCAE 4级)。B组(血小板减少)1例(16.6%)，C组3例(21.4%)(血小板减少3例，贫血1例)。CTCAE 3级肝毒性(天冬氨酸氨基转移酶升高)A组1例(8.3%)，C组1例(7.1%)。未观察到肾毒性。根据欧洲癌症研究和治疗组织的标准，A、B和C组的总体疾病应答率相似(分别为50.0%、50.0%和42.9%)，B组和C组的总体疾病控制率(83.3%)和C组(71.5%)高于A组(66.7%)。根据改良的PERCIST，发现疾病应答率较低，但疾病控制率相似。第1次PRRT后，A组(2.1%±40.8%)、B组和C组(−分别为38.7%±10.0%和−14.7%±20.0%)的SUVmax变化率略有增加(P=0.001)，第3次PRRT后3组均下降(A、B、C组：−6.9%±42.3%，−49.2%±30.9%)。−分别为11.9%±37.9%；P=0.044)。结论：177Lu-DOTA-EB-Tate的剂量递增至3.97GBq/周期似乎是可以耐受的。1.89和3.97GBq/周期的177Lu-DOTA-EB-Tate对肿瘤的控制效果优于1.17GBq/周期。
This study aimed to evaluate the safety and efficacy of multiple cycles of 177Lu-DOTA-Evans blue (EB)-TATE peptide receptor radionuclide therapy (PRRT) at escalating doses in neuroendocrine tumors (NETs). Methods: Thirty-two NET patients were randomly divided into 3 groups and treated with escalating doses. Group A received 1.17 ± 0.09 GBq/cycle; group B, 1.89 ± 0.53 GBq/cycle; and group C, 3.97 ± 0.84 GBq/cycle. The treatment was planned for up to 3 cycles. Treatment-related adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Treatment response was evaluated according to the European Organisation for Research and Treatment of Cancer criteria and modified PERCIST. Results: Administration of PRRT was well tolerated, without life-threatening adverse events (CTCAE grade 4). CTCAE grade 3 hematotoxicity was recorded in 1 patient (16.6%) in group B (thrombocytopenia) and 3 patients (21.4%) in group C (thrombocytopenia in 3, anemia in 1). CTCAE grade 3 hepatotoxicity (elevated aspartate aminotransferase) was recorded in 1 patient in group A (8.3%) and 1 patient in group C (7.1%). No nephrotoxicity was observed. According to the criteria of the European Organisation for Research and Treatment of Cancer, the overall disease response rates were similar in groups A, B, and C (50.0%, 50.0%, and 42.9%, respectively), and the overall disease control rates were higher in groups B (83.3%) and C (71.5%) than in group A (66.7%). According to modified PERCIST, a lower disease response rate but a similar disease control rate were found. When a comparable baseline SUVmax ranging from 15 to 40 was selected, the percentage change in SUVmax increased slightly in group A (2.1% ± 40.8%) but decreased significantly in groups B and C (−38.7% ± 10.0% and −14.7% ± 20.0%, respectively) after the first PRRT (P = 0.001) and decreased in all 3 groups after the third PRRT (groups A, B, and C: −6.9% ± 42.3%, −49.2% ± 30.9%, −11.9% ± 37.9%, respectively; P = 0.044). Conclusion: Dose escalations of up to 3.97 GBq/cycle seem to be well tolerated for 177Lu-DOTA-EB-TATE. 177Lu-DOTA-EB-TATE doses of 1.89 and 3.97 GBq/cycle were effective in tumor control and more effective than 1.17 GBq/cycle.