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。


背景无功能性胰腺神经内分泌肿瘤（NF-PanNETs）的切除对大多数患者来说是有效的。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 NF-PanNET 患者接受 177Lu 标记的 DOTA0-奥曲酸 (177Lu-DOTATATE) 新辅助手术后的安全性。方法 NEOLUPANET 是一项多中心、单组、II 期试验，受试者为患有散发性、可切除或潜在可切除 NF-PanNET 且复发风险高的患者。 68Ga 标记 DOTA PET 呈阳性的患者符合资格。所有患者均适合接受 177Lu-DOTATATE 新辅助治疗，然后进行手术。计算了 30 名患者的样本量，以根据预定的截止值测试术后并发症发生率。主要终点是安全性，反映为术后 90 天内的发病率和死亡率。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，共入组31例患者，其中26例完成4个周期的177Lu-DOTATATE。 31 名患者中有 18 名观察到部分放射学反应，其中 13 名患者病情稳定。未观察到疾病进展。 29 名接受手术的患者进行了 24 例 R0 切除和 4 例 R1 切除。一个肿瘤由于血管受累而无法切除。无术后死亡。 29 名患者中有 21 名出现术后并发症。七名患者出现严重并发症。 177Lu-DOTATATE 后生活质量保持稳定，手术后生活质量下降。结论 177Lu-DOTATATE 新辅助治疗对于 NF-PanNETs 患者是安全有效的。