Department of Medical Sciences, Uppsala University, Uppsala, Sweden,
Department of Nuclear Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
Neuroendocrinology. 2021;111(4):330-343. doi: 10.1159/000506746. Epub 2020 Feb 25.
To retrospectively analyze toxicity, progression-free survival (PFS), overall survival (OS), and their determinants in patients with advanced pancreatic neuroendocrine tumors (PanNETs), previously pretreated with chemothe-r-apy, undergoing peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE.
A total of 102 patients with advanced PanNETs, previously pretreated with one (67%) or several (33%) lines of chemotherapy, were included, of whom 90% had progressive disease and the majority (74.5%) had grade 2 tumors. 177Lu-DOTATATE, 7.4 GBq per cycle, was administered with 6- to 8-week intervals in 88% of patients utilizing a dosimetry-guided protocol until an absorbed dose of 23 Gy to the kidneys was reached.
A mean dose of 32 ± 10.9 GBq per patient was administered in 1-10 cycles starting a median of 36 months after PanNET diagnosis. The median follow-up was 34 months, the median PFS was 24 months, and the median OS was 42 months from start of PRRT. Independent risk factors for both progression and death were liver tumor burden >50%, more than one line of previous chemotherapy, and elevated alkaline phosphatase. Resection of the primary tumor was linked to longer survival. Bone marrow toxicity grade 3-4 occurred in 10.8%. One patient (1.0%) developed acute myeloid leukemia. Bone marrow toxicity was unrelated to type and length of previous chemotherapy, amount of administered activity, and absorbed dose to the bone marrow.
177Lu-DOTATATE therapy was feasible, highly effective, and safe in patients with advanced PanNETs heavily pretreated with chemotherapy. More than one line of chemotherapy was a therapy-related independent risk factor for shorter PFS and OS.
回顾性分析先前接受过化疗的晚期胰腺神经内分泌肿瘤（PanNETs）患者接受 177Lu-DOTATATE 肽受体放射性核素治疗（PRRT）的毒性、无进展生存期（PFS）、总生存期（OS）及其决定因素。
共纳入 102 例先前接受过 1 线（67%）或多线（33%）化疗的晚期 PanNETs 患者，其中 90%患者疾病进展，多数（74.5%）患者肿瘤分级为 2 级。88%的患者采用剂量指导方案，每 6-8 周进行一次治疗，每个周期给予 177Lu-DOTATATE7.4GBq，直至肾脏吸收剂量达到 23Gy。
从 PanNET 诊断后中位时间 36 个月开始，患者接受了 1-10 个周期，平均每个患者给予 32±10.9GBq 的剂量。中位随访时间为 34 个月，中位 PFS 为 24 个月，从 PRRT 开始中位 OS 为 42 个月。进展和死亡的独立危险因素包括肝肿瘤负荷>50%、有不止一条的既往化疗线数、碱性磷酸酶升高。原发肿瘤切除与生存时间延长相关。骨髓毒性 3-4 级的发生率为 10.8%。1 例（1.0%）患者发生急性髓系白血病。骨髓毒性与既往化疗的类型和长度、给予的放射性活度以及骨髓吸收剂量无关。
177Lu-DOTATATE 治疗在先前接受过多线化疗的晚期 PanNETs 患者中是可行的、高度有效的和安全的。有不止一条的化疗线是 PFS 和 OS 较短的治疗相关独立危险因素。
