Surgical Feasibility, Determinants, and Overall Efficacy of Neoadjuvant 177Lu-DOTATATE PRRT for Locally Advanced Unresectable Gastroenteropancreatic Neuroendocrine Tumors

OBJECTIVE: The aim of the study was to assess 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in neoadjuvant setting in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In addition, we also evaluated the variables associated with resectability of the primary following PRRT. MATERIALS AND METHODS: A total of 57 GEP-NETs with unresectable primary due to vascular involvement as defined using the National Comprehensive Cancer Network (NCCN) criteria given for pancreatic ductal adenocarcinoma (PDAC), who underwent 177Lu-DOTATATE without any prior surgery were included in this study. GEP-NETs were divided into two groups: Group1-without liver metastases (n = 23 patients) and Group2- with potentially resectable liver metastases (n = 34 patients). 177Lu-DOTATATE was administered with mixed amino acid-based renal protection with dose of 7.4 GBq (200 mCi) per cycle. Evaluation of surgical resectability following PRRT was done by using tri-phasic computed tomography (CT) imaging. Overall PRRT response was evaluated under four broad categories. The Kaplan–Meier product-limit method was used to calculate progression free survival (PFS) and overall survival (OS). Associations between variables and resectable primary after PRRT were analyzed by using Chi-square test at significant P value less than 0.05. RESULTS: Following 177Lu-DOTATATE, unresectable primary became resectable in 15 out of 57 (26.3%) patients {7 patients in group-1 and 8 patients in group-2}. Response (complete response and partial response) to PRRT was seen in 48 patients (84%), 23 patients (40%), 18 patients (31%) and 23 patients (40%) on symptomatic, biochemical, molecular imaging and anatomical imaging response evaluation criteria respectively. Estimated rates of PFS were 95% and 90% at 2 years in group1 and group2 patients respectively. The 2-years OS of combined both groups was 92.1%. Higher rate of resectable primary following PRRT was found in duodenal NET, GEP-NETs with absent regional lymph node involvement, size of primary