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Topic: Neuroendocrine Tumors

Management of hepatic metastases of well/moderately differentiated
neuroendocrine tumors of the digestive tract

Anna La Salvia , Stefano Partelli , Marco Tampellini , Domenico Tamburrino , Massimo Falconi ,
1
1
2
3
2
Giorgio V. Scagliotti , Maria Pia Brizzi 1
1
1 Division of Medical Oncology, Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Regione Gonzole 10, 10043 Orbassano, Italy.
2 Pancreatic Surgery Unit, San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy.
3 HPB Unit, Royal Free Hospital, London NW32QG, UK.
Correspondence to: Dr. Maria Pia Brizzi, Division of Medical Oncology, Department of Oncology, University of Turin, San Luigi Gonzaga
Hospital, Regione Gonzole 10, 10043 Orbassano, Italy. E-mail: mariapia.brizzi@email.it
A B S T R AC T
In neuroendocrine tumors (NETs), liver metastases (LM) represent the most crucial prognostic factor, irrespective of the primary
tumor site. At diagnosis, about 65-95% of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) show hepatic metastasis.
Management strategies of LM are heterogeneous and range from systemic therapy to liver-directed procedures. The type of systemic
therapy used is dependent on the grade and proliferation of the tumor and includes somatostatin analogues, interferon, m-Tor
and tyrosine kinase inhibitors, and chemotherapy. Angiographic liver-directed techniques, such as transarterial embolization/
chemoembolization and selective internal radiation therapy, offer excellent palliation for patients with liver-predominant disease.
In highly selected cases, liver transplantation and peptide receptor radionuclide therapy are considered. The relatively low disease
incidence and the diversity of presentation have led to a lack of well-conducted randomized controlled trials comparing the
efficacy of different treatment options. Experience indicates that surgery is the only treatment that offers potential for cure. For
unresectable lesions, the absence of data from rigorous trials limits the validity of many publications that detail management. In
this review we will discuss the existing approaches for hepatic metastases from GEP-NETs.

Key words: Gastroenteropancreatic carcinoids; metastases; systemic treatment

INTRODUCTION are a highly heterogeneous group of tumors comprising
low-grade (G1) and intermediate-grade (G2) NETs of
Neuroendocrine tumors (NETs) are rare neoplasms the gastrointestinal tract, typical and atypical carcinoids
originating from diffuse neuroendocrine cells. Even of the lung and thymus, and other cancers such as
though site of origin could sometimes be unknown, NETs medullary thyroid carcinoma and pheochromocytoma/
frequently involve any part of the gastrointestinal tract paraganglioma. [1,2] Finally, NETs could be associated with
(including endocrine pancreas), bronchopulmonary tree, paraneoplastic syndromes or with a supranormal production
thyroid, and thymus and have a wide range of malignant of hormones responsible for specific syndromes.
potential. The rapid evolution of clinical and pathological
findings has hampered a systematic classification of this The gastroenteropancreatic NETs (GEP-NETs) are the most
inhomogeneous family of tumors. The last World Health common NETs. Due to their relatively indolent course,
Organization (WHO) classification was published in they are frequently diagnosed in an advanced stage, [3,4] with
2010. Basically, NETs are classified according to tumor the development of liver metastases (LM) being the most
[1]
differentiation and site of occurrence. Highly aggressive, frequent clinical occurrence. [3-5] Metastatic spread to the
poorly differentiated neoplasms were defined as Grade-3 liver may be accompanied by a wide spectrum of clinical
neuroendocrine carcinomas (NECs) when originating presentations, from asymptomatic disease incidentally
from the gastrointestinal tract, or as small- or large-cell
NECs when appearing in the lung. Well- to moderately This is an open access article distributed under the terms of the Creative
[2]
differentiated neuroendocrine neoplasms (WMD-NEN) Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
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How to cite this article: La Salvia A, Partelli S, Tampellini M,
Tamburrino D, Falconi M, Scagliotti GV, Brizzi MP. Management of
hepatic metastases of well/moderately differentiated neuroendocrine
DOI: tumors of the digestive tract. J Cancer Metasta Treat 2016;2:294-303.
10.20517/2394-4722.2016.37
Received: 20-06-2016; Accepted: 18-07-2016.
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©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc.