Emerging Approaches in the Management of Patients with Neuroendocrine Liver Metastasis: Role of Liver-Directed and Systemic Therapies

• Published in: Journal of the American College of Surgeons Vol. 216; no. 1; pp. 123 - 134
• Main Authors: Mayo, Skye C., MD, MPH, Herman, Joseph M., MD, MSc, Cosgrove, David, MD, Bhagat, Nik, MD, Kamel, Ihab, MD, Geschwind, Jean-Francois H., MD, Pawlik, Timothy M., MD, MPH, PhD, FACS
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2013
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Catheter Ablation; Chemoembolization, Therapeutic; Chemoradiotherapy, Adjuvant; Hepatectomy; Humans; Infusions, Intra-Arterial; Liver Neoplasms - diagnosis; Liver Neoplasms - mortality; Liver Neoplasms - secondary; Liver Neoplasms - therapy; Liver Transplantation; Molecular Targeted Therapy; Neoplasm Staging; Neuroendocrine Tumors - diagnosis; Neuroendocrine Tumors - mortality; Neuroendocrine Tumors - secondary; Neuroendocrine Tumors - therapy; Surgery; Treatment Outcome; Y-90; progression-free survival; PNET; TACE; RFA; neuroendocrine liver metastasis; Yttrium-90; OLT; pancreatic neuroendocrine tumor; intra-arterial therapy; NELM; NET; PFS; radiofrequency ablation; transarterial chemoembolization; IAT; neuroendocrine tumors; orthotopic liver transplantation
• ISSN: 1072-7515; 1879-1190
• DOI: 10.1016/j.jamcollsurg.2012.08.027

Neuroendocrine tumors (NETs) are rare neoplasms arising from cells of the neuroendocrine system in a multitude of anatomic locations, and representing a wide range of histologies. Compared with other malignancies from the same organ (eg, pancreatic NET vs pancreatic ductal adenocarcinoma), NETs are often indolent in both biology and disease progression. However, metastasis will develop in almost 40% of patients with NETs during the course of their disease, most commonly to the liver. 1 In contrast to other malignancies, in a proportion of patients with neuroendocrine liver metastasis (NELM) disabling clinical symptoms can develop secondary to the production of specific biogenic amines and polypeptide hormones. Therefore, treatment of patients with NELM is focused on optimizing quality of life through reduction of such hormone-related symptoms, and improving survival in patients with disease amenable to liver-directed therapy, including hepatic resection, thermal ablation, and intra-arterial therapy (IAT). 2 - 8 To date, hepatic resection remains the only potentially curative option for patients with NELM, with 5-year survival after hepatectomy ranging from 60% to 80% in recent series. 6 - 11 Until recent reports of the use of somatostatin analogues in neuroendocrine tumors of mid-gut origin, and sunitinib and everolimus in patients with advanced pancreatic NETs (PNETs), there has been little success in the use of systemic therapy to treat patients with advanced NELM, with historic responses ranging from 15% to 20%. 12 - 15 As these systemic agents are not curative, there is still considerable interest in the use of liver-directed therapy to increase patient survival and address hormonally related symptoms. In addition to surgery, IAT has emerged as an alternative liver-directed approach to treat patients with NELM. We review the management of patients with NELM with an emphasis on clarifying the relative roles of surgery, IAT, as well as emerging systemic therapeutic agents. To accomplish this, we performed an extensive literature search in PubMed using medical subject headings (ie, neuroendocrine, carcinoid, liver metastasis, hepatic metastases, hepatectomy, liver resection, transplantation, intra-arterial therapy, radiation therapy, chemotherapy) to identify relevant articles for inclusion.