Therapeutic management of patients with gastroenteropancreatic neuroendocrine tumours

Abstract

Patients with neuroendocrine tumours (NETs) are best managed in a specialist centre as part of a multidisciplinary team comprising gastroenterologists, oncologists, endocrinologists, gastrointestinal and hepatopancreaticobiliary surgeons, pathologists, nuclear medicine physicians and technicians, radiologists, specialist nurses, pharmacists, biochemists and dieticians. This should ideally be led by a clinician with experience and interest in NETs. Although the number of medical treatments and clinical trials has increased in the decade, there is still a lack of prospective randomised trials; thus, management is mainly based on limited often single-centre studies, although there are now formal guidelines based on consensus expert opinion. We have outlined the current optimal management of patients with NETs. We have reviewed therapeutic options including surgery, somatostatin analogues and other biotherapies and peptide receptor-targeted therapy. We have discussed the challenge in managing hepatic metastases including hepatic artery embolisation, ablation and orthotopic liver transplant. In addition, we have briefly reviewed the emerging therapies such as the mammalian target of rapamycin and angiogenic inhibitors and the newer somatostatin analogues.

Differentiation of small bowel and pancreatic neuroendocrine tumors by gene-expression profiling

“…Treatment of pancreatic NETs (PNETs) has included combinations of streptozotocin and 5-fluorouracil and/or doxorubicin, with response rates of approximately 40% 7 . However, in non-pancreatic NETs, the response rate is only 25% 7 .…”

“…Treatment of pancreatic NETs (PNETs) has included combinations of streptozotocin and 5-fluorouracil and/or doxorubicin, with response rates of approximately 40% 7 . However, in non-pancreatic NETs, the response rate is only 25% 7 . More recently, Sunitinib and Everolimus have been demonstrated to lead to improved disease free survival for patients with advanced PNETs 8, 9 .…”

A comparison of Ki-67 and mitotic count as prognostic markers for metastatic pancreatic and midgut neuroendocrine neoplasms

“…Most commonly arising from the gastrointestinal tract, gastroenteropancreatic NENs (GEP-NENs) have a variable prognosis, with survival ranging from 6 months to more than 20 years (Yao et al , 2008). As the therapeutic options continue to expand it is increasingly important to define robust prognostic markers to inform clinical decision making (Khan and Caplin, 2011). The Ki-67 proliferation index and mitotic count (MC) have proved to be the most useful prognostic histological markers, and have been incorporated into international grading systems (Ramage et al , 2012).…”

The use of targeted therapies in pancreatic neuroendocrine tumours: patient assessment, treatment administration, and management of adverse events

“…For patients with functioning tumours (defined as tumours that secrete hormones that cause physiological symptoms) and for those with positive Octreoscan (Mallinkrodt Pharmaceuticals, Dublin, Ireland), short-and long-acting somatostatin analogues (e.g. octreotide, lanreotide) may be used to reduce symptoms associated with hormone hypersecretion, including diarrhoea and flushing, potentially improving quality of life (QoL) [Kulke et al 2012;Khan and Caplin, 2011;Gardner-Roehnelt, 2012]. Octreotide also has been shown to have antitumour efficacy in patients with advanced midgut NETs and has been approved by the European Medicines Agency (EMA) for this indication [Rinke et al 2009].…”

“…Among patients with nonfunctioning tumours, available treatment choices include surgery, chemotherapy, radiopeptide therapy for metastatic disease, liver-targeted therapies for progressive liver metastases, and palliative care to reduce pain and other tumour symptoms [National Comprehensive Cancer Network, 2012]. Local palliative radiotherapy can also be used to control local symptoms [Oberg et al 2004;Khan and Caplin, 2011]. Historically, systemic chemotherapy has had little impact on pNETs, and its toxicity has precluded widespread use of aggressive combination chemotherapy regimens in patients with pNETs [Burns and Edil, 2012].…”