Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.
J Nucl Med. 2013 Nov;54(11):1857-61. doi: 10.2967/jnumed.112.119347. Epub 2013 Sep 5.
Myelosuppression may be the dose-limiting toxicity in peptide receptor radionuclide therapy (PRRT). The aim of this study was to investigate the incidence, severity, and reversibility of long-term hematotoxicity in a large cohort of patient undergoing PRRT with (177)Lu-octreotate for metastatic neuroendocrine tumors. The impact of potential risk factors, including initial cytopenia, advanced bone metastatic disease, previous chemotherapy, and cumulative administered activity, and the protective effects of splenectomy were of particular interest.
A total of 632 PRRT courses were performed in 203 patients with metastatic neuroendocrine tumors. A mean activity of 7.9 GBq of (177)Lu-octreotate was administered per treatment cycle, with a goal of 4 courses at standard intervals of 3 mo. Hematologic parameters were determined before each treatment course, at 2- to 4-wk intervals between the courses, 8-12 wk after the last course of PRRT, and at 3-month intervals for further follow-up. Toxicity was recorded with Common Terminology Criteria for Adverse Events (version 3.0).
Myelodysplastic syndrome as a delayed adverse event was documented in 3 patients (1.4%). Relevant but reversible hematotoxicity (grade 3 or 4) occurred in 23 patients (11.3%) and 29 administrations (4.6%), with leukopenia in 2.7% and thrombocytopenia in 1.7%. The mean time to blood count recovery was 12 mo after the termination of PRRT (range, 3-22 mo). The only preexisting factor that contributed to hematotoxicity was initial cytopenia (P < 0.001). A high level of cumulative administered activity (>29.6 GBq) was associated with relevant leukopenia (P < 0.001). None of the patients with a history of splenectomy developed grade 3 or 4 hematotoxicity, and splenectomy was inversely associated with the incidence and degree of leukopenia (P = 0.02) and thrombocytopenia (P = 0.03).
PRRT-induced myelosuppression is almost invariably reversible and rarely requires clinical measures. Administered activity and initial cytopenia are the only factors contributing to myelosuppression, whereas splenectomy may exert a protective effect.
本研究旨在调查在接受 177Lu-奥曲肽肽受体放射性核素治疗（PRRT）的大队列患者中，长期血液毒性的发生率、严重程度和可逆性。特别关注的是潜在危险因素的影响，包括初始细胞减少症、晚期骨转移疾病、先前的化疗以及累积给予的活性，以及脾切除术的保护作用。
203 名转移性神经内分泌肿瘤患者共进行了 632 次 PRRT 治疗。每个治疗周期给予平均 7.9GBq 的 177Lu-奥曲肽，目标是每 3 个月标准间隔进行 4 个疗程。在每次治疗前、疗程之间的 2-4 周、PRRT 最后一次疗程后 8-12 周以及进一步随访的 3 个月间隔测定血液学参数。使用不良事件通用术语标准（版本 3.0）记录毒性。
3 名患者（1.4%）记录了骨髓增生异常综合征作为延迟不良事件。23 名患者（11.3%）和 29 次给药（4.6%）出现相关但可逆的血液毒性（3 级或 4 级），白细胞减少症发生率为 2.7%，血小板减少症发生率为 1.7%。PRRT 终止后血液计数恢复的平均时间为 12 个月（范围为 3-22 个月）。唯一导致血液毒性的预先存在的因素是初始细胞减少症（P<0.001）。高累积给予的活性（>29.6GBq）与相关的白细胞减少症相关（P<0.001）。无脾切除术史的患者均未发生 3 级或 4 级血液毒性，脾切除术与白细胞减少症（P=0.02）和血小板减少症（P=0.03）的发生率和严重程度呈负相关。
PRRT 诱导的骨髓抑制几乎总是可逆的，很少需要临床措施。给予的活性和初始细胞减少症是导致骨髓抑制的唯一因素，而脾切除术可能具有保护作用。
