BACKGROUND Resection of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) is curative in most patients. The potential benefits of neoadjuvant treatments have, however, never been explored. The primary aim of this study was to evaluate the safety of neoadjuvant 177Lu-labelled DOTA0-octreotate (177Lu-DOTATATE) followed by surgery in patients with NF-PanNETs. METHODS NEOLUPANET was a multicentre, single-arm, phase II trial of patients with sporadic, resectable or potentially resectable NF-PanNETs at high-risk of recurrence; those with positive 68Ga-labelled DOTA PET were eligible. All patients were candidates for neoadjuvant 177Lu-DOTATATE followed by surgery. A sample size of 30 patients was calculated to test postoperative complication rates against predefined cut-offs. The primary endpoint was safety, reflected by postoperative morbidity and mortality within 90 days. Secondary endpoints included rate of objective radiological response and quality of life. RESULTS From March 2020 to February 2023, 31 patients were enrolled, of whom 26 completed 4 cycles of 177Lu-DOTATATE. A partial radiological response was observed in 18 of 31 patients, and 13 patients had stable disease. Disease progression was not observed. Twenty-four R0 resections and 4 R1 resections were performed in 29 patients who underwent surgery. One tumour was unresectable owing to vascular involvement. There was no postoperative death. Postoperative complications occurred in 21 of 29 patients. Severe complications were observed in seven patients. Quality of life remained stable after 177Lu-DOTATATE and decreased after surgery. CONCLUSION Neoadjuvant treatment with 177Lu-DOTATATE is safe and effective for patients with NF-PanNETs.

中文翻译：

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新辅助 177Lu-DOTATATE 治疗无功能胰腺神经内分泌肿瘤 （NEOLUPANET）：多中心 II 期研究。


背景 切除无功能胰腺神经内分泌肿瘤 （NF-PanNETs） 对大多数患者是治愈性的。然而，新辅助治疗的潜在益处从未被探索过。本研究的主要目的是评估新辅助 177Lu 标记的 DOTA0-奥曲酸盐 （177Lu-DOTATATE） 后手术对 NF-PanNETs 患者的安全性。方法 NEOLUPANET 是一项多中心、单臂、II 期试验，针对复发风险高的散发、可切除或可能可切除的 NF-PanNET 患者;68Ga标记的DOTA PET阳性者符合条件。所有患者均适合新辅助 177Lu-DOTATATE 后手术。计算 30 名患者的样本量，以根据预定义的临界值测试术后并发症发生率。主要终点是安全性，反映在术后 90 天内的发病率和死亡率上。次要终点包括客观放射学反应率和生活质量。结果 2020 年 3 月至 2023 年 2 月，共纳入 31 例患者，其中 26 例完成了 4 个周期的 177Lu-DOTATATE。31 例患者中有 18 例观察到部分放射学反应，13 例患者病情稳定。未观察到疾病进展。在 29 例接受手术的患者中进行了 24 例 R0 切除术和 4 例 R1 切除术。1 例肿瘤由于血管受累而无法切除。术后无死亡。29 例患者中有 21 例发生术后并发症。在 7 例患者中观察到严重并发症。177Lu-DOTATATE 后生活质量保持稳定，术后生活质量下降。结论 177Lu-DOTATATE 新辅助治疗对 NF-PanNETs 患者安全有效。