The Role of Intraarterial 177Lu-Dotatate Therapy in the Treatment of Hepatic Metastasis from Neuroendocrine Tumors

Purpose: The propensity of currently practiced intravenous lutetium-177 (¹⁷⁷Lu)–Dotatate therapy to produce side effects warrants any novel techniques to reduce the side effects without compromising the dose delivered to the target areas. Gastroenteropancreatic neuroendocrine tumors have the tendency to metastasize to the liver but seldom to other organs. We have postulated the selective intraarterial administration of ¹⁷⁷Lu-Dotatate to hepatic arteries will reduce unwanted side effects through increasing the dose delivered to target areas because of the first-pass extraction of the radiopeptides by the tumor.

Materials and Methods: A prospective evaluation was done of 654 patients who underwent intraarterial ¹⁷⁷Lu-Dotatate therapy for hepatic neuroendocrine metastasis in our institution from June 2014 to January 2021. A CAPTEM-PRRT (capecitabine–temozolomide with peptide receptor radionuclide therapy) regimen based on Columbia University protocol as adopted in our study. Response Evaluation Criteria in Solid Tumors (RECIST) and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) criteria were used to response evaluation based on preprocedure and follow-up 68Ga-DOTANOC positron emission tomography–computed tomography.

Results: We found that 88% (complete response + partial response) of patients had a significant radiologic tumor response, and 12% showed a stabilization of the disease. No patients were found to have progressive disease. All patients tolerated the procedure well, with none experiencing any significant procedure-related acute side effects. None of the patients developed acute radiation-induced liver disease or renal toxicity. Only 14 patients developed grade 1 to 2 hematologic toxicity. Only 10 patients developed a transient increase of hepatic enzymes, which normalized subsequently with no decrease in total bilirubin levels. Fifty percent of patients showed partial response to therapy according to RECIST criteria, and the remaining patients showed stable disease. All patients reported significant improvement in symptoms and sense of well-being after treatment initiation.

Conclusions: Our initial experience of intra arterial administration of ¹⁷⁷Lu-Dotatate therapy in patients with liver-dominant metastases from neuroendocrine tumors is promising, feasible, safe, and tolerable. The preliminary therapeutic potential of this therapy is encouraging. However, further prospective studies are needed to show its impact in improving clinical outcomes, median survival, and progression-free survival.