Peptide receptor radionuclide therapy for recurrent neuroendocrine tumors after liver transplantation

doi:10.3748/wjg.121126

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Dec 7, 2026; 32(45): 121126
Published online Dec 7, 2026. doi: 10.3748/wjg.121126

Peptide receptor radionuclide therapy for recurrent neuroendocrine tumors after liver transplantation

Qi-Ming Zheng, Chi-Yi Chen, Li Zhang, Ji-San Sun, Hong-Hai Wang, Yan Xie, Qing-Jun Guo, Wen-Tao Jiang

Qi-Ming Zheng, Wen-Tao Jiang, Department of Liver Transplantation, First Central Hospital of Tianjin Medical University, Tianjin 300192, China

Qi-Ming Zheng, Chi-Yi Chen, Li Zhang, Ji-San Sun, Hong-Hai Wang, Yan Xie, Qing-Jun Guo, Wen-Tao Jiang, Department of Liver Transplantation, Tianjin First Central Hospital, Tianjin 300192, China

Qi-Ming Zheng, Wen-Tao Jiang, Department of Liver Transplantation, Tianjin Key Laboratory of Molecular Diagnosis and Treatment of Liver Cancer, Tianjin 300192, China

Co-first authors: Qi-Ming Zheng and Chi-Yi Chen.

Co-corresponding authors: Qing-Jun Guo and Wen-Tao Jiang.

Author contributions: Zheng QM and Chen CY conceived and designed the study, performed the experiments, and made equivalent and indispensable contributions to this manuscript as co-first authors; Zheng QM contributed to the drafting of the manuscript; Zheng QM, Chen CY, and Zhang L contributed to the analysis and interpretation of data; Zheng QM, Chen CY, Sun JS, Xie Y, Guo QJ, and Jiang WT contributed to the critical revision of the manuscript; Zhang L, Sun JS, Wang HH, Xie Y, Guo QJ, and Jiang WT contributed to the acquisition of data; Guo QJ and Jiang WT contributed equally as co-corresponding authors; and all authors read and approved the final version of the manuscript.

Supported by the Key Project of Tianjin Science and Technology Bureau Applied Basic Research, No. 23JCZDJC01200; the Independent Research Fund of the Institute of Transplant Medicine at Nankai University, No. NKTM2023004; and the Tianjin Key Medical Discipline Construction Project, No. TJYXZDXK-3-006A-1.

Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the Tianjin First Central Hospital (No. KELUNSHEN 2026-51).

Informed consent statement: Due to the retrospective study design, this study waived the need for written informed consent.

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

Data sharing statement: The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Corresponding author: Wen-Tao Jiang, MD, PhD, Principal Investigator, Department of Liver Transplantation, First Central Hospital of Tianjin Medical University, No. 2 Baoshan West Road, Xiqing District, Tianjin 300192, China. jiangwentao@nankai.edu.cn

Received: March 17, 2026
Revised: April 15, 2026
Accepted: April 24, 2026
Published online: December 7, 2026
Processing time: 212 Days and 17.9 Hours

Abstract

BACKGROUND

Liver transplantation (LT) is a curative intervention for neuroendocrine tumor liver metastasis (NETLM) patients with tumor burden and rapid progression, yet tumor recurrence is a bottleneck restricting survival. Long-term immunosuppression impairs tolerance to antitumor therapies and increases risk, leaving options for patients with recurrence. Peptide receptor radionuclide therapy (PRRT) is a therapy for somatostatin receptor-positive (SSTR+) neuroendocrine tumors; its efficacy and safety in liver transplant recipients with recurrent NETLM under everolimus immunosuppression remain unvalidated due to lack of comparative studies.

AIM

To evaluate the efficacy and safety of lutetium Lu 177 dotatate (¹⁷⁷Lu-DOTATATE) PRRT in patients with recurrent SSTR+ G2 NETLM after LT under immunosuppression.

METHODS

In this retrospective comparative cohort study at Tianjin First Central Hospital (2019-2025), 15 patients (7 PRRT and 8 controls) received everolimus immunosuppression plus conventional antitumor therapy; the PRRT group also received ¹⁷⁷Lu-DOTATATE. Group assignment was based on multidisciplinary decisions, patient preference and drug availability, not randomization. Toxicities and tumor responses graded per Common Terminology Criteria for Adverse Events version 5.0 and Response Evaluation Criteria in Solid Tumors version 1.1, respectively. Prognostic indicators were progression-free survival (PFS) and overall survival (OS). Survival curves were plotted by Kaplan-Meier method and compared using log-rank test.

RESULTS

Baseline characteristics were comparable between groups, with the exception of age (P = 0.019). The median follow-up period was 33 months (range: 6-72 months). In the PRRT group, the primary toxicities observed were grade I-III bone marrow suppression (7/7, 100%) and grade I-II proteinuria (4/7, 57.1%). All of these adverse events resolved with symptomatic management, except for one patient who discontinued PRRT due to persistent thrombocytopenia. In terms of efficacy, the PRRT group achieved an objective response rate of 14.3% and a disease control rate of 85.7%, compared with 0% and 37.5% in the control group (not significant). Kaplan-Meier analysis demonstrated superior PFS in the PRRT group (P = 0.028), whereas no significant difference was observed in OS between the two groups.

CONCLUSION

For patients with SSTR+ G2 NETLM, PRRT with standard-of-care treatment demonstrates improved PFS, suggesting promising therapeutic option for patient population. However, these findings require validation in larger, multicenter studies with follow-up.

Keywords: Liver transplantation; Neuroendocrine tumors; Liver metastasis; Peptide receptor radionuclide therapy; Recurrence; Progression-free survival

Core Tip: This retrospective comparative cohort study evaluates lutetium Lu 177 dotatate (¹⁷⁷Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT) combined with everolimus in somatostatin receptor-positive G2 neuroendocrine tumor liver metastases after liver transplantation. In 7 PRRT-treated patients vs 8 controls, PRRT achieved a disease control rate of 85.7% and significantly improved progression-free survival (log-rank P = 0.028), with manageable hematologic toxicity (grade III in 28.6%) and no graft rejection. These hypothesis-generating findings suggest PRRT as a promising option for this rare cohort.