We assessed ¹⁷⁷Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in the neoadjuvant setting in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We also evaluated the variables associated with resectability of the primary tumor after PRRT. Methods: This study included 57 GEP-NET patients who had a primary tumor that was unresectable (because of vascular involvement as defined using the pancreatic ductal adenocarcinoma criteria of the National Comprehensive Cancer Network) and who underwent ¹⁷⁷Lu-DOTATATE therapy without any prior surgery. They were categorized into 2 groups: 23 patients without liver metastases (group 1) and 34 patients with potentially resectable liver metastases (group 2). ¹⁷⁷Lu-DOTATATE was administered with mixed amino acid–based renal protection at a dose of 7.4 GBq (200 mCi) per cycle. Surgical resectability was evaluated using triphasic contrast-enhanced abdominal CT imaging at 3 different time points during the PRRT course. Four broad categories of overall PRRT response were evaluated. The Kaplan–Meier product-limit method was used to calculate progression-free survival (PFS) and overall survival (OS). Associations between variables and a resectable primary tumor after PRRT were analyzed using the ² test, with a P value of less than 0.05 considered statistically significant. Results: After ¹⁷⁷Lu-DOTATATE therapy, the unresectable primary tumor became resectable in 15 of 57 (26.3%) patients (7 patients in group 1 and 8 patients in group 2). A complete or partial response to PRRT was seen in 48 patients (84%), 23 patients (40%), 18 patients (31%), and 23 patients (40%) using symptomatic, biochemical, molecular imaging, and anatomic imaging criteria, respectively. Estimated rates of PFS were 95% and 90% at 2 y in groups 1 and 2, respectively. The 2-y OS of the 2 groups combined was 92.1%. The rate at which the primary tumor was resectable after PRRT was significantly higher in patients who had duodenal neuroendocrine tumors, patients who had GEP-NETs with no regional lymph node involvement, patients for whom the primary tumor was smaller than 5 cm, patients for whom liver metastases were no larger than 1.5 cm, patients for whom there were no more than 3 liver metastases, and patients for whom ¹⁸F-FDG uptake in the primary tumor had an SUV_max of less than 5. Conclusion: In a moderate fraction of GEP-NET patients, with or without liver metastases, whose primary tumor was unresectable because of vascular involvement, the primary tumor converted from unresectable to resectable after ¹⁷⁷Lu-DOTATATE therapy, signifying that neoadjuvant PRRT can be considered in such patients. The effective control of symptoms, favorable morphologic and functional imaging response, and durable PFS and OS that we observed after ¹⁷⁷Lu-DOTATATE PRRT may lead to less morbidity and mortality in these patients.

我们评估了胃肠胰神经内分泌肿瘤 (GEP-NET) 患者新辅助治疗中的¹⁷⁷ Lu-DOTATATE 肽受体放射性核素治疗 (PRRT)。我们还评估了与 PRRT 后原发肿瘤可切除性相关的变量。方法：本研究纳入了 57 名 GEP-NET 患者，这些患者患有无法切除的原发肿瘤（因为血管受累，根据国家综合癌症网络的胰腺导管腺癌标准定义），并且接受了^{177 例}Lu-DOTATATE 治疗，且之前未进行任何手术。他们被分为 2 组：23 名无肝转移的患者（第 1 组）和 34 名有可能可切除肝转移的患者（第 2 组）。 ¹⁷⁷ Lu-DOTATATE 给予基于混合氨基酸的肾脏保护，剂量为每个周期 7.4 GBq (200 mCi)。在 PRRT 过程中的 3 个不同时间点使用三相增强腹部 CT 成像评估手术可切除性。评估了总体 PRRT 反应的四大类。 Kaplan-Meier 乘积限法用于计算无进展生存期 (PFS) 和总生存期 (OS)。使用²检验分析变量与 PRRT 后可切除的原发肿瘤之间的关联， P值小于 0.05 被认为有统计学意义。结果：经过^{177 次}Lu-DOTATATE 治疗后，57 名患者中有 15 名 (26.3%) 患者中不可切除的原发肿瘤变得可切除（第 1 组中 7 名患者，第 2 组中 8 名患者）。 根据症状、生化、分子影像和解剖影像标准，48 名患者 (84%)、23 名患者 (40%)、18 名患者 (31%) 和 23 名患者 (40%) 出现 PRRT 完全或部分缓解， 分别。第 1 组和第 2 组的 2 年 PFS 估计率分别为 95% 和 90%。 2 组的 2 年 OS 合计为 92.1%。 PRRT 后原发肿瘤可切除率在十二指肠神经内分泌肿瘤患者、有 GEP-NET 但无区域淋巴结受累的患者、原发肿瘤小于 5 cm 的患者、肝转移灶大小不超过 1.5 cm，肝转移灶不超过 3 个，原发肿瘤¹⁸ F-FDG 摄取 SUV _max小于 5 的患者。结论：中度部分GEP-NET患者，无论有无肝转移，其原发肿瘤因血管受累而无法切除，经过¹⁷⁷ Lu-DOTATATE治疗后，原发肿瘤由不可切除转为可切除，提示此类患者可以考虑新辅助PRRT。我们在¹⁷⁷ Lu-DOTATATE PRRT 后观察到的症状有效控制、良好的形态和功能成像反应以及持久的 PFS 和 OS 可能会降低这些患者的发病率和死亡率。