Peptide Receptor Radionuclide Therapy for Recurrent Neuroendocrine Tumor Liver Metastases After Liver transplantation: A Case Series

Abstract

Objective: This study evaluated the toxicity and efficacy of Lu-177-DOTATATE peptide receptor radionuclide therapy (PRRT) under everolimus immunosuppression in patients with somatostatin receptors-positive (SSTR+) and grade 1/2 (G1/G2) neuroendocrine tumor liver metastasis (NETLM) who relapsed after liver transplantation (LT), aiming to provide evidence-based evidence for multidisciplinary management.

Methods: Data were retrospectively collected from seven patients with recurrent NETLM after LT treated with PRRT between April 2023 and June 2025.

Inclusion criteria: stable liver tumor ≥ 6 months prior to LT; G1/G2; SSTR (+); and post-LT immunosuppression with everolimus (4 cases of everolimus monotherapy, 3 cases combined with low-dose tacrolimus). Assessments included pre- and post-PRRT imaging, laboratory tests, and everolimus blood concentrations (target range 3-8 ng/mL); toxicity was assessed according to CTCAE v5.0, and efficacy was assessed according to RECIST 1.1. PRRT was administered with 1 to 4 cycles and a cumulative dose of 175 to 709 mCi, and 3 patients received concomitant treatment with long-acting octreotide. Follow-up until death or final follow-up.

Results: Seven patients were included. Primary foci: pancreas in 3 cases and rectum in 4 cases; hepatic metastatic load >50% prior to transplantation. Everolimus blood levels were stable (3-8 ng/mL) during PRRT and there was no rejection. Major toxicities were hematologic: 2 cases of grade III, 4 cases of grade II and 1 case of grade I myelosuppression (1 case discontinued PRRT due to persistent severe myelosuppression); and 4 cases of grade I-II proteinuria (possibly related to everolimus nephrotoxicity).

Efficacy: 1 partial remission (PR), 5 stable disease (SD), 1 progression disease (PD), with a disease control rate (DCR) of 85.7%. No severe hepatic or renal impairment, infection or other serious adverse events occurred during treatment and follow-up.

Conclusions: PRRT combined with everolimus-based immunosuppression has demonstrated controllable safety and preliminary antitumor activity in patients with relapsed NETLM after LT who have been strictly screened, but myelosuppression requires close monitoring and timely symptomatic treatment.