Nuclear Medicine, University Hospital, Bonn, Germany.
J Nucl Med. 2012 Nov;53(11):1663-9. doi: 10.2967/jnumed.112.107482. Epub 2012 Sep 17.
Previous radiation therapy of the liver is a contraindication for performing (90)Y microsphere radioembolization, and its safety after internal radiation exposure through peptide receptor radionuclide therapy (PRRT) has not yet been investigated.
We retrospectively assessed a consecutive cohort of 23 neuroendocrine tumor (NET) patients with liver-dominant metastatic disease undergoing radioembolization with (90)Y microspheres as a salvage therapy after failed PRRT. Toxicity was recorded throughout follow-up and reported according to Common Terminology Criteria for Adverse Events (version 3). Radiologic (response evaluation criteria in solid tumors), biochemical, and symptomatic responses were investigated at 3 mo after treatment, and survival analyses were performed with the Kaplan-Meier method (log-rank test, P < 0.05).
The median follow-up period after radioembolization was 38 mo (95% confidence interval, 18-58 mo). The mean previous cumulative activity of (177)Lu-DOTA-octreotate was 31.8 GBq. The mean cumulative treatment activity of (90)Y microspheres was 3.4 ± 2.1 GBq, administered to the whole liver in a single session (n = 8 patients), in a sequential lobar fashion (n = 10 patients), or to only 1 liver lobe (n = 5 patients). Only transient, mostly minor liver toxicity (no grade 4) was recorded. One patient (4.3%) developed a gastroduodenal ulcer (grade 2). The overall response rates for radiologic, biochemical, and symptomatic responses were 30.4%, 53.8%, and 80%, respectively. The median overall survival was 29 mo (95% confidence interval, 4-54 mo) from the first radioembolization session and 54 mo (95% confidence interval, 47-61 mo) from the first PRRT cycle. A tumor proliferation index Ki-67 greater than 5% predicted shorter survival (P = 0.007).
Radioembolization is a safe and effective salvage treatment option in advanced NET patients with liver-dominant tumor burden who failed or reprogressed after PRRT. The lack of relevant liver toxicity despite high applied (90)Y activities and considerable previous cumulative activities of (177)Lu-octreotate is noteworthy and disputes internal radiation exposure by PRRT as a toxicity risk factor in subsequent radioembolization.
先前的肝脏放射治疗是进行(90)Y 微球放射性栓塞的禁忌症,其在肽受体放射性核素治疗(PRRT)后通过内部放射暴露的安全性尚未得到研究。
我们回顾性评估了 23 例神经内分泌肿瘤(NET)患者的连续队列,这些患者患有肝优势转移性疾病,在 PRRT 失败后接受(90)Y 微球进行挽救性放射栓塞。在整个随访过程中记录毒性,并根据不良事件通用术语标准(第 3 版)进行报告。在治疗后 3 个月时,进行放射学(实体瘤反应评估标准)、生化和症状反应的调查,并通过 Kaplan-Meier 方法进行生存分析(对数秩检验,P < 0.05)。
放射栓塞后中位随访时间为 38 个月(95%置信区间,18-58 个月)。先前累积的(177)Lu-DOTA-octreotate 的平均活动度为 31.8GBq。(90)Y 微球的平均累积治疗活动度为 3.4±2.1GBq,单次给予整个肝脏(8 例患者),按顺序叶式给予(10 例患者),或仅给予 1 个肝叶(5 例患者)。仅记录到短暂的、主要为轻微的肝毒性(无 4 级)。1 例患者(4.3%)发生胃十二指肠溃疡(2 级)。放射学、生化和症状反应的总体缓解率分别为 30.4%、53.8%和 80%。从第一次放射栓塞治疗开始的总生存中位数为 29 个月(95%置信区间,4-54 个月),从第一次 PRRT 周期开始的总生存中位数为 54 个月(95%置信区间,47-61 个月)。Ki-67 肿瘤增殖指数大于 5%预测生存期更短(P = 0.007)。
对于在 PRRT 后失败或进展的肝优势肿瘤负荷的晚期 NET 患者,放射栓塞是一种安全有效的挽救治疗选择。尽管应用了较高的(90)Y 活性和相当大的先前累积(177)Lu-octreotate 活性,但没有明显的肝脏毒性,这表明 PRRT 引起的内部放射暴露不是随后放射栓塞的毒性危险因素。