Department of Nuclear Medicine, Medical University of Warsaw, ul. Banacha 1 a, 02-097, Warsaw, Poland.
European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, Karlsruhe, Germany.
Eur J Nucl Med Mol Imaging. 2021 Oct;48(11):3595-3605. doi: 10.1007/s00259-021-05350-y. Epub 2021 Apr 15.
Glioblastoma is the most common and malignant primary brain tumour, with a poor prognosis. Introduction of new treatment options is critically important. The study aimed to assess the appropriateness of escalation doses and toxicity of [Ac]Ac-DOTA-SP therapy.
A total of 21 patients (age of 43.0 ± 9.5 years), with histologically confirmed recurrent or conversion glioblastoma grade 4 following a standard therapy, have been included in the study. One to 2 intracavitary port-a-cath systems were stereotactically inserted. Patients were treated with escalation dose protocol with 10, 20 and 30 MBq per cycle totally 1-6 doses of [Ac]Ac-DOTA-SP in 2-month intervals. Therapeutic response was monitored by clinical performance status and MRI imaging.
Treatment was well tolerated with mostly mild temporary adverse effects (oedema, epileptic seizures, aphasia, hemiparesis) mainly in the group of patients treated with 30 MBq of [Ac]Ac-DOTA-SP. Only one patient treated with 30 MBq revealed thrombopenia grade 3. There was no other grade 3 and 4 toxicity related to [Ac]Ac-DOTA-treatment in all groups. The median overall survival time from the primary diagnosis (OS-d) was 35.0 months and from the diagnosis of the recurrence/conversion (OS-r/c) was 13.2 months. From the start of treatment with [Ac]Ac-DOTA-SP, the median PFS was 2.4 months, and the OS-t was 9.0 months. There were no statistically significant differences between the investigated dose escalation groups.
Treatment of recurrent glioblastoma with [Ac]Ac-DOTA-SP is safe and well tolerated up to 30 MBq per cycle. The escalation dose protocol showed good tolerability. Only mild temporary adverse effects were observed. No remarkable haematological, kidney and liver toxicity was seen.
胶质母细胞瘤是最常见和最恶性的原发性脑肿瘤，预后不良。引入新的治疗方案至关重要。本研究旨在评估 [Ac]Ac-DOTA-SP 治疗的递增剂量和毒性的适宜性。
共纳入 21 例（年龄 43.0±9.5 岁）经组织学证实为标准治疗后复发或转化的 4 级胶质母细胞瘤患者。立体定向插入 1 至 2 个颅内端口系统。患者接受递增剂量方案治疗，每个周期给予 10、20 和 30 MBq 的 [Ac]Ac-DOTA-SP，2 个月间隔 1-6 个周期。通过临床绩效状态和 MRI 成像监测治疗反应。
治疗耐受性良好，大多数患者出现短暂的轻度不良反应（水肿、癫痫发作、失语、偏瘫），主要见于接受 30 MBq [Ac]Ac-DOTA-SP 治疗的患者组。仅 1 例患者出现 3 级血小板减少症。所有组均无与 [Ac]Ac-DOTA 治疗相关的 3 级和 4 级毒性。从原发性诊断（OS-d）的中位总生存时间为 35.0 个月，从复发/转化的诊断（OS-r/c）为 13.2 个月。从开始接受 [Ac]Ac-DOTA-SP 治疗起，中位 PFS 为 2.4 个月，OS-t 为 9.0 个月。在研究的递增剂量组之间没有统计学上的显著差异。
用 [Ac]Ac-DOTA-SP 治疗复发性胶质母细胞瘤是安全的，每个周期最多可耐受 30 MBq。递增剂量方案显示出良好的耐受性。仅观察到轻微的暂时不良反应。未观察到明显的血液学、肾脏和肝脏毒性。
