Navigating the landscape of liver transplantation in neuroendocrine tumors: A comprehensive scoping review

Table 2 Systematic reviews identified in the search and the most relevant retrospective cohort studies

Study design	Ref.	n	Population	Comparison	Outcome
Systematic reviews	Moris et al[11], 2017	279 patients transplanted for NET with liver metastases in the combined series	Patients with NET liver metastases, with unresectable diffuse disease or extensive liver disease	Liver transplantation vs non-surgical treatments; prognostic comparison by histological grade, liver involvement, Ki-67, pancreatic vs gastrointestinal primary	Overall survival at 1, 3, and 5 years: Approximately 89%, 69%, 63%; high recurrence rates (31%-57%) depending on criteria; negative prognostic factors include elevated Ki-67, > 50% liver involvement, pancreatic primary
	Fan et al[12], 2015	706	Adult patients with liver metastases from unresectable NETs undergoing liver transplantation	Liver transplant vs palliative resection or non-surgical treatment	Overall survival (5 years approximately 50%-70%), disease-free survival (30%), prognostic factors (age > 50, pancreatic primary, high Ki-67, poor differentiation, > 50% liver involvement)
	Rossi et al[13], 2014	213	Patients with gastroenteropancreatic NETs with well-differentiated liver metastases, well-defined selection criteria (Ki-67 < 10%, age < 55, stable disease, resected primary tumor, < 50% of the liver involved)	Liver transplantation vs no transplantation; comparison between different selection criteria (location of the primary tumor; degree of differentiation, liver involvement, pre-LT stability)	5-year survival rate up to approximately 90% in well-selected cases; but tumor recurrence remains a problem; beneficiaries are patients with removed primary tumors, low proliferation, and stable disease
	Stump et al[14], 2013	Without a defined n	Adult patients with NET liver metastases (resectable and unresectable)	Liver resection vs non-surgical treatment; LT vs other therapies; resection of the primary tumor vs non-resection	Planned outcomes: Overall survival, progression-free survival, quality of life; establish selection criteria and impact of adjuvant/neoadjuvant therapies
	Máthé et al[15], 2011	89	Patients undergoing liver transplantation for pancreatic neuroendocrine metastases	Various comparators, such as the type of neoplasm and simultaneous resections	Following liver transplantation, the cumulative overall survival rates at 1, 3, and 5 years were 71%, 55%, and 44%, respectively; VIPomas exhibited the highest overall survival. Recurrence-free survival rates at 1, 3, and 5 years were 84%, 47%, and 47%, respectively
Retrospective cohort	Sampaio et al[1], 2023	11 LT due to NET metastasis	Eight patients with NETs of gastrointestinal origin and three with unknown primary sites	No comparison group	LT was favorable in terms of overall survival and disease-free survival in selected patients. Strict patient selection is necessary. The ideal timing for transplant indication remains controversial
	Kuncewicz et al[17], 2023	19 LT of unresectable NET	19 patients undergoing LT from the pancreatic site	No comparison group	Ki-67 index ≥ 5% is a risk factor for worse OS, and RFS recipient age ≥ 55 years for worse RFS; Ki-67 ≥ 5% is a factor for worse OS
	Eshmuminov et al[27], 2023	455 patients included in hepatectomies and LT	225 patients undergoing LT for NET	230 patients undergoing liver resections	Improved OS in LT; this effect depends on the selection criteria (Milan criteria and low-grade tumor)
	Maspero et al[33], 2022	104 patients diagnosed with NET	48 patients in the LT group - only patients meeting the Milan criteria were included	56 patients in the liver resection group	The LT group showed improved survival compared to the liver resection group
	Korda et al[7], 2019	10 LT due to NET metastasis	Patients transplanted due to NET metastasis	No comparison group	Primary pancreatic lesions and elevated Ki67 are associated with higher recurrence rates
	Mazzaferro et al[25], 2016	88 patients with NET meeting the Milan criteria for liver transplantation	42 patients undergoing LT	44 non-surgical treatment options	LT in patients with NET metastasis, in patients with established criteria show excellent OS
	Grąt et al[32], 2014	12 patients with NET metastasis undergoing LT	Patients undergoing LT due to unresectable NET	No comparison group	Excellent long-term OS survival rate in unresectable NET
	Le Treut et al[23], 2013	213 LT for NET performed in 35 European centers	Patients undergoing LT due to unresectable NET	No comparison group	LT in non-resectable NET showed OS at 5 years between 60%-80%; the appropriate timing for transplantation remains uncertain

NET: Neuroendocrine tumor; LT: Liver transplantation; OS: Overall survival; RFS: Recurrence-free survival.