Liver transplantation for unresectable pancreatic neuroendocrine tumors with liver metastases in an era of transplant oncology

Abstract

Patients with pancreatic neuroendocrine tumors (pNETs) very often present with a metastatic disease at the first diagnosis. Liver transplantation (LT) for unresectable pNET with liver metastases (pNETLM) has been described to prolong survival in highly selected patients, although outcomes were worse than those of patients who underwent LT for gastrointestinal NETLM (GI-NETLM). In this review, several proposed criteria are described with their rationale and controversies. Most of the data used to establish these criteria do not reflect the recent improvements of non-surgical treatments that has changed the landscape of treatment for pNETs, including the development of peptide receptor radionuclide therapy and molecular-targeted agents (sunitinib and everolimus). Properly designed studies are necessary to define the role of down-staging and bridging therapy prior to LT incorporating systemic chemotherapy using these molecular-targeted agents. Also, given the indolent nature of low or intermediate grade pNETs, the best endpoint to compare the efficacy of each treatment option for patients with pNETLM has yet to be determined. Lastly, the definition of "unresectable" remains ambiguous. The indication of the conventional technique of two-staged liver resection with portal vein embolization or the new technique of associating liver partition and portal vein ligation for staged hepatectomy to expand the resectability of wide-spread metastatic liver tumors has been controversial. In an era of transplant oncology, LT should be the last resort for patients who are considered unresectable and otherwise untreatable after an exhaustive multidisciplinary team discussion by all experts in the field. In conclusion, although its long-term outcomes have been promising, the role of LT for unresectable pNETLM as a curative or palliative treatment remains unclear. A well-designed randomized control study is required to elucidate the clinical impact of LT for pNETLM.

Liver transplantation in patients with neuroendocrine tumors: a case series and literature review

“…NET heterogeneity with inconsistent patient selection criteria lead to a wide range of five-year survival (33%-97%) and disease-free survival (DFS) rates (32%-87%) ( 3 , 6 , 8 , 12 , 13 , 17 , 20 , 25 - 32 ), considerably varying according to tumor grade, stage, primary site, age, and period from diagnosis, with reported improvement of median overall survival (9.3 years) ( 32 )…”

“…The relatively slow growing pattern of metastases and their long confinement to the liver make transplantation a reasonable long-term potentially curative option ( 3 , 12 , 14 , 16 , 17 ). Due to disease rarity, heterogeneous tumor parameters, and a lack of clear and prospectively validated patient selection criteria, the transplantation results are highly variable and insufficient to make definitive recommendations ( 9 , 17 - 20 ).…”

Rare breast and subcutaneous metastases from pancreatic neuroendocrine tumor: a case report

“…Metastatic PNETs have a worse 5-year overall survival rate (40–60%) than the metastatic intestinal neuroendocrine tumors (56–83%) [17]. Breast metastases from extramammary malignancies are uncommon in general (accounting for only 0.5–1.3% of cases) [18].…”

“…everolimus) or multipotential blocking agents against vascular endothelial growth factor and other receptor blocking agents, as well as peptide receptor radionuclide therapy or cytotoxic chemotherapy [16]. The development of molecular targeted agents has changed the landscape of treatment for PNETs [17]. According to the European Neuroendocrine Tumor Society (commonly known as ENETS) consensus guidelines, resection of metastases of grade 3 pancreatic neuroendocrine carcinoma is generally not recommended but may be considered in individual cases with isolated resectable metastases [2].…”

<p>Primary site surgery for elderly patients with distant metastatic pancreatic neuroendocrine tumor: to do or not to do?</p>

“…As a rare neoplasm, pancreatic neuroendocrine tumor (pNET) originates from pancreatic neuroendocrine cells and may occur in various organs, including lung, gastrointestinal tract, pancreas, etc 1,2. pNETs represent approximately 7% of all NETs and account for 1–2% of all pancreatic malignancies 1–3. Over the past several decades, the incidence of pNET has been increasing in the United States 4.…”