欧洲神经内分泌肿瘤学会（ENETS）分级 3（G3）神经内分泌肿瘤（NEN）中的肽受体放射性核素治疗（PRRT）-单机构回顾性分析。
Peptide receptor radionuclide therapy (PRRT) in European Neuroendocrine Tumour Society (ENETS) grade 3 (G3) neuroendocrine neoplasia (NEN) - a single-institution retrospective analysis.
机构信息
Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Department of Nuclear Medicine and PET, Singapore General Hospital, Singapore, Singapore.
出版信息
Eur J Nucl Med Mol Imaging. 2018 Feb;45(2):262-277. doi: 10.1007/s00259-017-3821-2. Epub 2017 Sep 12.
PURPOSE
Grade 3 NENs are aggressive tumours with poor prognosis. PRRT+/- radiosensitising chemotherapy is a potential treatment for disease with high somatostatin receptor (SSTR) expression without spatially discordant FDG-avid disease. We retrospectively evaluated the efficacy of PRRT in G3 NEN.
METHODS
Kaplan-Meier estimation was used to determine progression-free survival (PFS) and overall survival (OS) defined from start of PRRT. Subgroup analysis was performed for patients with Ki-67 ≤ 55% and >55%. Anatomical response (RECIST 1.1) and toxicity 3 months after PRRT was determined. Disease control rate (DCR) was defined as complete response (CR), partial response (PR) and stable disease (SD) of those with prior progression.
RESULTS
28 patients (M = 17; age 16-78 years; Ki-67 ≤ 55% = 22) were reviewed. 17 patients had pancreatic, 5 small bowel, 3 large bowel, 2 bronchial and 1 unknown primary disease. 25/28 had significant FDG-avid disease prior to treatment. Most had Lu-DOTA-octreotate (median cumulative activity 24.4 GBq, median 4 cycles). Twenty patients had radiosensitising chemotherapy. 89% were treated for disease progression; 79% after prior chemotherapy. Median follow-up was 29 months. The median PFS was 9 months for all patients. 16 patients died (Ki-67 ≤ 55% = 11; Ki-67 > 55% = 5) with median OS of 19 months. For Ki-67 ≤ 55% (N = 22), the median PFS was 12 months and median OS 46 months. For Ki-67 > 55% (N = 6), the median PFS was 4 months and median OS 7 months. On CT imaging, DCR at 3 months post-PRRT was 74%, 35% (8/23) PR and 39% (9/23) SD. Eleven patients received further PRRT due to recrudescent disease after response. Five patients developed progression of discordant FDG-avid disease and were referred for targeted therapy/chemotherapy. Grade 3 and 4 lymphopenia and thrombocytopenia occurred in five and five patients, respectively. No renal or liver toxicity related to treatment was seen.
CONCLUSIONS
PRRT achieves clinically relevant disease control with acceptable toxicity in G3 NENs.
目的
3 级神经内分泌肿瘤是一种侵袭性强、预后不良的肿瘤。对于表达高 somatostatin receptor (SSTR) 且无空间不一致的 FDG-avid 疾病的疾病，PRRT+/-放射增敏化疗是一种潜在的治疗方法。我们回顾性评估了 PRRT 在 G3 NEN 中的疗效。
方法
采用 Kaplan-Meier 估计法确定 PRRT 开始后无进展生存期（PFS）和总生存期（OS）。对 Ki-67≤55%和>55%的患者进行亚组分析。在 PRRT 后 3 个月评估解剖学反应（RECIST 1.1）和毒性。疾病控制率（DCR）定义为先前进展患者的完全缓解（CR）、部分缓解（PR）和稳定疾病（SD）。
结果
共回顾 28 例患者（M=17；年龄 16-78 岁；Ki-67≤55%=22）。17 例为胰腺，5 例为小肠，3 例为大肠，2 例为支气管，1 例为未知原发灶。28 例患者中有 25 例在治疗前有明显的 FDG-avid 疾病。大多数患者接受 Lu-DOTA-octreotate（累积活动中位数 24.4GBq，中位数 4 个周期）治疗。20 例患者接受放射增敏化疗。89%的患者因疾病进展而接受治疗；79%的患者在接受化疗后进展。中位随访时间为 29 个月。所有患者的中位 PFS 为 9 个月。16 例患者死亡（Ki-67≤55%=11；Ki-67>55%=5），中位 OS 为 19 个月。对于 Ki-67≤55%（N=22），中位 PFS 为 12 个月，中位 OS 为 46 个月。对于 Ki-67>55%（N=6），中位 PFS 为 4 个月，中位 OS 为 7 个月。在 CT 成像上，PRRT 后 3 个月的 DCR 为 74%，35%（8/23）为 PR，39%（9/23）为 SD。11 例患者因反应后复发疾病而接受进一步的 PRRT。5 例患者出现不伴 FDG-avid 疾病进展，接受靶向治疗/化疗。5 例和 5 例患者分别出现 3 级和 4 级淋巴细胞减少症和血小板减少症。未观察到与治疗相关的肾或肝毒性。
结论
PRRT 可在 3 级神经内分泌肿瘤中实现具有临床意义的疾病控制，且毒性可接受。
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