The treatment of neuroendocrine tumours with radionuclides

Abstract

Neuroendocrine tumours (NETs) include a wide variety of heterogeneous neoplasms which have varying secretory capacities and often produce distinct clinical syndromes, and show a wide spectrum of behaviour. The term is particularly used to refer to tumours arising from secretory cells of the gastro-enteropancreatic system, either from the neuroendocrine cells in the islets of the pancreas, islet cell tumours, or from the neuroendocrine cells diffusely spread throughout the gut. These latter have been referred to loosely as 'carcinoids', but only around 10% are associated with a true carcinoid syndrome. Some 80–90% express somatostatin receptors, which is the basis of their identification and localisation with 111In-octreotide scintiscanning; this may be used to identify the primary tumour and locate the extent of metastases. We have also recently shown that around 40% show uptake with the radionuclide 123I-mIBG, which may be important therapeutically. Where surgery is non-curative, treatment should aim at improving the quality of life and hopefully extending survival. This includes specific anti-metabolic therapy and the use of somatostatin analogues, particularly long-acting ones (octreotide/Sandostatin LAR; Lanreotide Autogel). Where there is positive 123I-mIBG uptake, we use targetted radiotherapy with 131I-mIBG, usually giving 200 mCi every 6 months to a total dose of 1000–1200 mCi, although we are now trialling larger doses of 300–500 mCi at brief intervals. Our data suggest that complete responses are very rare, but partial tumour responses associated with symptomatic improvement are frequently seen, and survival is probably prolonged. The scanning agent 111In-octreotide can be used for therapy due to the secondary production of Auger electrons, but high doses need to be used, adverse effects are common and objective responses are very few. More recently, 90Y-octreotide has been shown to be safe and effective in some cases, particularly gastrinomas and metastatic insulinomas, while therapy with 177Lu-octreotate shows tumoural responsivity in ˜30% of patients with stabilisation of previously-progressive tumours in ˜60%, especially smaller tumours or metastases. It is possible that combination therapy with radionuclides of varying penetration will be even more effective. It is important to maintain the patients' quality of life, and use other measures such as nutritional support, adequate analgesia, localised radiotherapy where appropriate, and niacin supplementation in patients with the carcinoid syndrome. Finally, the involvement of a multi-disciplinary team in a centre with extensive experience offers the patient the best outcome.