Efficacy of intra-arterial [177Lu]Lu-DOTATATE vs. continuation intravenous [177Lu]Lu-DOTATATE peptide receptor radionuclide therapy in nonresponding locally advanced inoperable or liver-dominant metastatic gastroenteropancreatic neuroendocrine tumors

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) demonstrating liver-dominant inoperable metastatic diseases or locally advanced inoperable tumors may at times show reduced efficacy for intravenous peptide receptor radionuclide therapy (PRRT). AIMS AND OBJECTIVES: To determine and compare the outcome of intra-arterial [177Lu]Lu-DOTATATE PRRT in GEP-NET with locally advanced inoperable primary or liver-dominant metastases who had shown no response after at least two cycles of intravenous [177Lu]Lu-DOTATATE, as compared to those patients who continued intravenous [177Lu]Lu-DOTATATE only. MATERIALS AND METHODS: GEP-NET patients with locally advanced inoperable primary or liver metastatic disease, who exhibited nonresponsive disease (either stable or progressive disease on anatomical imaging evaluation) after at least two cycles of intravenous [177Lu]Lu-DOTATATE PRRT, were administered intra-arterial [177Lu]Lu-DOTATATE PRRT (group A). For comparison, matched controls [age, gender, primary site, tumor grade, proliferation index, disease burden, and [18F]fluorodeoxyglucose (FDG) PET/computed tomography status] who had received only intravenous [177Lu]Lu-DOTATATE PRRT (group B) were selected retrospectively. The data were compared and analyzed for response assessments across three categories (symptomatic, including various quality-of-life scores; biochemical; and imaging), survival outcomes, and toxicity profiles. RESULTS: A total of 33 GEP-NET patients (group A-11 and group B-22) were included. Symptomatic alleviation was slightly higher in group A compared with group B (75 vs. 66.8%), with higher quality-of-life (QoL) scores in group A. According to RECIST 1.1, group A had a 36.3% objective response rate compared with 13.6% in group B. Group A had a higher disease control rate (90.8%) than group B (77.2%). The median progression-free survival (PFS) was significantly longer in group A (not attained) compared with group B (median PFS of 22 months; P < 0.05). No major toxicity was observed in either group. CONCLUSION: Intra-arterial [177Lu]Lu-DOTATATE resulted in a higher response rate, symptomatic relief, improved QoL, and prolonged PFS in patients whose disease remained nonresponsive after intravenous [177Lu]Lu-DOTATATE. Prospective randomized controlled trials can further validate the incorporation of intra-arterial PRRT into the management of GEP-NETs.