Endocrine Abstracts

Background: Surgical resection of Nonfunctioning Pancreatic Neuroendocrine Tumor (NF-PanNET) is curative in most of the cases. Neoadjuvant treatments in patients with resectable NF-PanNET at high-risk of recurrence have never been investigated. Aim of this study was to test the safety and efficacy of neoadjuvant PRRT with ¹⁷⁷Lu-DOTATATE followed by surgery in patients with resectable high-risk NF-PanNET.

Methods: This was a multi-center single-arm phase 2 trial. Treatment was PRRT with ¹⁷⁷Lu-DOTATATE (LutatheraÒ) followed by surgery in patients with high-risk of recurrence resectable NF-PanNET. “High-risk NF-PanNET” was defined by the presence of at least one of the following characteristics: tumor size > 4 cm, nearby organ/s invasion, Ki67 >10%, vascular invasion, single liver metastasis, nodal involvement. The primary endpoints were postoperative morbidity and mortality. The secondary endpoint was the rate of objective radiological response.

Results: Among 34 patients screened, 31 were enrolled in the study. Twenty-six (84%) patients tolerated 4 cycles of ¹⁷⁷Lu-DOTATATE whereas 4 patients did not complete 4 cycles for adverse events or unsafe absorbed dose. One patient voluntary interrupted treatment after 2 cycles and 2 patients refused to undergo surgery after ¹⁷⁷Lu-DOTATATE. No patient had progressive disease after neoadjuvant ¹⁷⁷Lu-DOTATATE. A partial radiological response was observed in 18 patients (58%) whereas 13 patients (42%) had stable radiological disease. Overall, 29 patients underwent surgery after a median period of 119 days (113–142.5 days) from the last cycle of ¹⁷⁷Lu-DOTATATE. Surgical resection of NF-PanNET was achieved in 28 patients (96.5%) whereas one patient underwent only exploratory laparotomy for unresectable vascular invasion. Pancreaticoduodenectomy (n=11) and distal pancreatectomy (n=11) were the most frequent types of operation. At final histology, the majority of patients who underwent resection had a NF-PanNET G2 (n=16) and a nodal involvement (N1) was present in the 52% of cases. There was no postoperative mortality. Severe postoperative complications occurred in the 24% of patients and postoperative pancreatic fistula was the most frequent complication after surgery (34%).

Conclusion: Neoadjuvant PRRT with ¹⁷⁷Lu-DOTATATE followed by surgery for NF-PanNET is safe and effective demonstrating evidence of a high rate-of radiological response. (ClinicalTrials.gov registration: NCT04385992).

Abstract ID 23692