Intra-arterial peptide receptor radionuclide therapy (IA-PRRT) in patients with SSTR-expressing neuroendocrine neoplasms: short- and long-term safety and efficacy for up to 13 years

Intravenous peptide receptor radionuclide therapy (IV-PRRT) has established its role in the treatment algorithm of somatostatin receptor (SSTR)-expressing neuroendocrine neoplasms (NENs). This study aims to evaluate the safety and efficacy of intra-arterial PRRT (IA-PRRT) in patients with SSTR-expressing NENs. <b>Methods:</b> The radiopharmaceutical was injected by a dedicated radionuclide infusion set <i>via</i> an intra-arterial catheter entering the femoral artery access site, with a microcatheter placed in the common hepatic artery or other selected artery <i>via</i> a standard access using the common femoral artery. Morphologic and molecular responses were evaluated in accordance with RECIST 1.1 and the EORTC criteria with ⁶⁸Ga-SSTR PET/CT. Kaplan-Meier survival analysis was performed to calculate median progression-free survival (PFS) and overall survival (OS). Short- and long-term toxicities were documented in accordance with the CTCAE, version 5.0. <b>Results:</b> 52 patients with SSTR-expressing NENs treated with intra-arterial PRRT with ¹⁷⁷Lu- or ⁹⁰Y-DOTATOC/DOTATATE from February 1999 to January 2019 were reviewed. The median follow-up time was 94.4 mo. Safety analysis demonstrated anemia (grade 1, n=4), leukocytopenia (grade 1, n=3; grade 2, n=1; grade 3, n=1), thrombocytopenia (grade 1, n=11) following IA-PRRT compared to baseline. No severe nephrotoxicity or liver dysfunction was observed after IA-PRRT. According to RECIST 1.1, the disease control rate at 3-6 mo after IA-PRRT was 89.4%, and the best objective response rate was 36.2%. For the entire cohort received IA-PRRT (n=52), the median PFS and OS were 29.9 and 68.9 months, respectively. In the subgroup of patients with neuroendocrine liver metastases receiving liver directed IA-PRRT, the median PFS and OS for patients with hepatic only tumor with or without lymph node metastases were significantly longer than those with extrahepatic-tumor (PFS, 35.9 mo <i>vs.</i> 21.6 mo, p=0.0128; OS, 80.1 mo <i>vs.</i> 50.5 mo, p=0.0470). <b>Conclusions:</b> Intra-arterial PRRT is well-tolerated, safe and effective in patients with SSTR-expressing neuroendocrine neoplasms. The median OS and PFS appear promising, particularly in patients with hepatic tumor burden. No additional severe hematotoxicity, nephrotoxicity or hepatotoxicity was observed after IA-PRRT and during long-term follow-up. In particular, this procedure can be considered in patients with neuroendocrine liver metastases only or liver metastases mainly. Prospective studies are warranted to verify these results.