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

Abstract

The aim of the study was to assess 177 Lu-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 METHODSA 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 177 Lu-DOTATATE without any prior surgery were included in this study. GEP-NETs were divided into two groups: Group1without liver metastases (n=23 patients) and Group2-with potentially resectable liver metastases (n=34 patients). 177 Lu-DOTATATE was administered with mixed amino acidbased 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. RESULTSFollowing 177 Lu-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

Value of Peptide Receptor Radionuclide Therapy as Neoadjuvant Treatment in the Management of Primary Inoperable Neuroendocrine Tumors

“…It has been demonstrated to be effective not only in improving progression-free survival (PFS) but also overall survival (OS) in those patients (3)(4)(5). Moreover, in selected cases, it may enable the resection of primarily inoperable tumors (6)(7)(8). For that reason, the rationale for the use of PRRT as first-line treatment may be especially valuable in case of extensive disease burden at the time of diagnosis, hormonal syndromes resistant to somatostatin analogs, or a chance for subsequent curative surgery.…”

Targeted Cancer Therapy: What’s New in the Field of Neuroendocrine Neoplasms?

“…Furthermore, recent and encouraging evidence is arising about the potential role for PRRT in the neoadjuvant setting. In this context, 177Lu-DOTATATE was reported to convert 15 out of 57 (26.3%) unresectable primary GEP NETs into resectable ones in a small non-controlled study [135]. Further prospective and randomized studies are needed to confirm these promising data.…”

Radiolabeled Somatostatin Analogs—A Continuously Evolving Class of Radiopharmaceuticals

“…NENs and their liver metastases are often highly perfused, and the intra-arterial route can exploit the first-pass effect to treat liver-dominant disease more efficiently. Such an approach can also be used for inoperable primary tumors to downstage the disease in the neoadjuvant setting [ 25 , 26 ]. However, large comparative prospective trials supporting its wider use are missing.…”