Treatment of Liver Metastases in Patients with Neuroendocrine Tumors: A Comprehensive Review

Abstract

Patients diagnosed with Neuroendocrine Tumors (NET) often are also diagnosed with Neuroendocrine Liver Metastases (NLM) during the course of their disease. NLM can cause significant morbidity and mortality, oftentimes much more than compared to patients with NET. Treatment options have been limited in the past, focusing on surgical resections, for which only a minority of patients are candidates. However, developments of new treatment modalities have progressed rapidly and patients with NLM now have significantly more options, including surgical-directed therapies; liver-directed therapies; and nonsurgical, non-liver-directed therapies. This review provides information about the roles of hepatic resection, orthotopic liver resection, radiofrequency ablation, hepatic artery embolization and hepatic artery chemoembolization, hepatic artery radioembolization and selective internal radiation therapy, peptide receptor radionuclide therapy, systemic chemotherapy, biotherapies including somatostatin analogs and interferon-α, vascular endothelial growth factor and mTOR targets, and microRNA-regulated pathways. Given these new options, the clinician can tailor therapy specific to the patient diagnosed with NLM, thereby giving the patient the best possible chance of prolonged survival.

A population-based study of outcomes in patients with gastrointestinal neuroendocrine tumours

“…Our evidence is concordant with that of other authors who documented improved outcomes with surgery for metastatic disease. 15,17,18 The survival rate in our study for R0 resections is higher than that reported in other studies (55%-80%). 5,9,16,18 We attribute this improvement, in part, to the use of postoperative radioisotope therapy to minimize the risk of recurrence and control tumour growth.…”

Intractable hypoglycaemia in a patient with advanced carcinoid syndrome successfully treated with hepatic embolization

“…Bland embolization improves symptoms, tumour markers and radiological appearances. 10 HACE delivers chemotherapy (e.g. with doxorubicin) attached to the embolic agent.…”

An Overview of the Surgical Management of Hepatic Neuroendocrine Metastases

“…Between 1988 and 2011, 185 liver transplants were performed in the United States for neuroendocrine LM, and the overall 5 year survival was only 57.8%, comparably lower than transplants performed for other reasons (74% for all other patients), as well as lower than the survival rate following resection [9]. It is potentially an option for young patients who fit into the following criteria [9]; 1) LM not amenable to resection 2) Resection of primary malignancy at least 1 year prior to evaluation 3) No evidence of unresectable extra-hepatic metastases 4) Disease stability for at least 1 year 5) Failure of non-operative treatments…”

“…Despite the high tumour recurrence rate found in most case series, increase in survival time and the symptom control achieved are why aggressive surgical resection is still the mainstay of treatment. It has been found that even incomplete surgical resections (R1 or R2) can offer a survival benefit to patients, with a 5 year survival of 70% and 60% respectively in a prospective study of 47 patients [9].…”

“…Between 46-93% of patients with NETs have liver involvement (NLM) at the time of diagnosis [1]. The disease course of these tumours is far from universally indolent, and metastatic involvement of the liver typically represents the greatest threat of morbidity and mortality posed by these malignancies [9]. This is due to excess tumour production and replacement of the normal hepatic parenchyma.…”