We intended to identify the prognostic factors and the results of interventions on patients with liver metastatic midgut carcinoids. Five institutions that are part of United Kingdom and Ireland neuroendocrine tumour (NET) group took part in this study. Patients were included if they had histology proven NET of midgut origin and liver metastases at the time of the study. Clinical and biochemical data were collected retrospectively from hospital charts, pathology reports, radiology reports and biochemistry records for each patient. Three hundred and sixty patients were included in the study. The median survival from date of diagnosis was 7.69 years (confidence interval (CI) 6.40-8.99) and 5.95 years (CI 5.02-6.88) from date of diagnosis of liver metastases. On univariate analysis, increasing age at diagnosis, increasing urinary hydroxyindole acetic acid levels, increasing plasma chromogranin A levels, high Ki67, high tumour volume and treatment with chemotherapy were identified as factors associated with a significantly poorer outcome. Resection of liver metastases, resection of small bowel primary, treatment with somatostatin analogue therapy and treatment with peptide receptor therapy were associated with improved prognosis. Multivariate analysis revealed that age at diagnosis (P=0.014), Ki67 level (P=0.039) and resection of primary (P=0.015) were independent predictors of survival. This is the largest study to our knowledge looking specifically at the prognosis and clinical course of patients with liver metastatic midgut NETs. For the first time, we have shown that Ki67 and resection of primary are independent predictors of survival for this group of patients.

/pdf/midgut-neuroendocrine-tumours-with-liver-metastases-results-1xe934e1f3.pdf

Midgut neuroendocrine tumours with liver metastases: results of the UKINETS study.

Nuclear medicine plays a pivotal role in the imaging and treatment of neuroendocrine tumours (NETs). Somatostatin receptor scintigraphy (SRS) with [(111)In-DTPA(0)]octreotide has proven its role in the diagnosis and staging of gastroenteropancreatic NETs (GEP-NETs). New techniques in somatostatin receptor imaging include the use of different radiolabelled somatostatin analogues with higher affinity and different affinity profiles to the somatostatin receptor subtypes. Most of these analogues can also be labelled with positron-emitting radionuclides that are being used in positron emission tomography imaging. The latter imaging modality, especially in the combination with computed tomography, is of interest because of encouraging results in terms of improved imaging quality and detection capabilities. Considerable advances have been made in the imaging of NETs, but to find the ideal imaging method with increased sensitivity and better topographic localisation of the primary and metastatic disease remains the ultimate goal of research. This review provides an overview of the currently used imaging modalities and ongoing developments in the imaging of NETs, with the emphasis on nuclear medicine and puts them in perspective of clinical practice. The advantage of SRS over other imaging modalities in GEP-NETs is that it can be used to select patients with sufficient uptake for treatment with radiolabelled somatostatin analogues. Peptide receptor radionuclide therapy (PRRT) is a promising new tool in the management of patients with inoperable or metastasised NETs as it can induce symptomatic improvement with all Indium-111, Yttrium-90 or Lutetium-177-labelled somatostatin analogues. The results that were obtained with [(90)Y-DOTA(0),Tyr(3)]octreotide and [(177)Lu-DOTA(0),Tyr(3)]octreotate are even more encouraging in terms of objective tumour responses with tumour regression and documented prolonged time to progression. In the largest group of patients receiving PRRT, treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate, a survival benefit of several years compared with historical controls has been reported.

/pdf/nuclear-medicine-techniques-for-the-imaging-and-treatment-of-4dz4avu4d9.pdf

Nuclear medicine techniques for the imaging and treatment of neuroendocrine tumours

Radionuclide Therapy in Neuroendocrine Tumours: A Systematic Review

Metaiodobenzylguanidine (MIBG) is structurally similar to the neurotransmitter norepinephrine and specifically targets neuroendocrine cells including some neuroendocrine tumors. Iodine-131 (I-131)-labeled MIBG (I-131 MIBG) therapy for neuroendocrine tumors has been performed for more than a quarter-century. The indications of I-131 MIBG therapy include treatment-resistant neuroblastoma (NB), unresectable or metastatic pheochromocytoma (PC) and paraganglioma (PG), unresectable or metastatic carcinoid tumors, and unresectable or metastatic medullary thyroid cancer (MTC). I-131 MIBG therapy is one of the considerable effective treatments in patients with advanced NB, PC, and PG. On the other hand, I-131 MIBG therapy is an alternative method after more effective novel therapies are used such as radiolabeled somatostatin analogs and tyrosine kinase inhibitors in patients with advanced carcinoid tumors and MTC. No-carrier-aided (NCA) I-131 MIBG has more favorable potential compared to the conventional I-131 MIBG. Astatine-211-labeled meta-astatobenzylguanidine (At-211 MABG) has massive potential in patients with neuroendocrine tumors. Further studies about the therapeutic protocols of I-131 MIBG including NCA I-131 MIBG in the clinical setting and At-211 MABG in both the preclinical and clinical settings are needed.

Current Consensus on I-131 MIBG Therapy.

Backgroundmeta-[131I]Iodobenzylguanidine (131I-MIBG) has been used to treat patients with disseminated neuroendocrine tumours (NET). However, so far there is limited information related to the efficacy of this agent beyond the normal 6-month assessment period. Before we can assume that such treatmen

Long-term efficacy of low activity meta-[131I]iodobenzylguanidine therapy in patients with disseminated neuroendocrine tumours depends on initial response.

The management of metastatic neuroendocrine tumors incorporates multimodal therapy with surgery, biotherapy, and chemotherapy. Tumor-targeted therapies using radiolabeled octreotide and meta-iodobenzylguanidine (mIBG) represent a novel treatment approach. The aim of this study was to evaluate the effectiveness of 131I-mIBG in the treatment of metastatic midgut carcinoid tumors. survival outcomes were assessed for patients treated at two regional cancer centers and then compared. One center used 131I-mIBG routinely in the management of metastatic carcinoid tumors (center A), and the other did not use this modality (center B). Only patients with histologically proven metastatic carcinoid tumor shown, or thought most likely, to be of midgut origin were included in the study. During the period 1980 to 2002, a series of 58 patients from center A with metastatic carcinoid tumor arising from the midgut underwent multimodality therapy with the addition of 131I-mIBG. Their median age was 64 years. The median dose of 131I-mIBG administered was 6751 MBq, and there was an average of 2.8 treatments per patient. During the same period, 58 patients with metastatic carcinoid were treated at center B with similar multimodality therapy without the use of 131I-mIBG therapy. Their median age was 65 years. Survivals at 3 and 5 years were 77% and 63%, respectively (95% CI 47–75), for group A. The 3- and 5-year survivals for group B were 56% and 47% (95% CI 34–59), respectively. The mean follow-up was 6.6 years for group A and 5.0 years for group B. Although retrospective in nature, this study suggests that the addition of 131I-mIBG therapy to the treatment protocol of patients with metastatic midgut carcinoid tumors prolongs survival.

131I-meta-iodobenzylguanidine in the management of metastatic midgut carcinoid tumors.

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131I-meta-iodobenzylguanidine in the management of metastatic midgut carcinoid tumors.