scholarly journals How I treat neuroendocrine tumours

ESMO Open ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. e000811
Author(s):  
Barbara Kiesewetter ◽  
Markus Raderer
Keyword(s):  
Neuroendocrine Tumours ◽  
Kinase Inhibitor ◽  
Primary Tumour ◽  
Somatostatin Receptor ◽  
Treatment Strategies ◽  
Somatostatin Analogues ◽  
Receptor Expression ◽  
Minor Role ◽  
Endocrine Activity ◽  
Therapeutic Concepts

Neuroendocrine tumours (NETs) constitute a heterogeneous group of neoplasms characterised by variable endocrine activity and somatostatin receptor expression, with the latter allowing the use of targeted therapeutic concepts. Currently accepted treatment strategies for advanced well-differentiated NET include somatostatin analogues octreotide and lanreotide, peptide receptor radionuclide therapy using radiolabelled somatostatin analogues, mammalian target of Rapamycin inhibitor everolimus, tyrosine kinase inhibitor sunitinib, interferon alpha and classical cytostatic, such as streptozotocin-based and temozolomide-based treatment. Indication, use and approval of these treatments differ based on primary tumour origin, grading and symptomatic burden and require an optimised multidisciplinary cooperation of medical oncologists, endocrinologists and nuclear medicine specialists. Interestingly, hot topics in oncology including immunotherapy and use of next-generation-sequencing techniques currently play a minor role for the treatment of NETs. The recent revision of the WHO classification including the recognition of the novel NET G3 category allows for potentially more tailored treatment strategies in the near future. However, this new entity also poses a therapeutic challenge as only limited data are currently available. The present article aims to provide an overview on our personal treatment concepts for advanced NETs with a focus on tumours of gastroenteropancreatic origin.

scholarly journals Treatment of Advanced Hepatocellular Carcinoma with Somatostatin Analogues: A Review of the Literature

2019 ◽  
Vol 20 (19) ◽  
pp. 4811
Author(s):  
Hendrik Reynaert ◽  
Isabelle Colle
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Current Knowledge ◽  
Primary Liver Cancer ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Receptor Expression ◽  
Surrounding Tissue ◽  
Advanced Hepatocellular Carcinoma

Hepatocellular carcinoma, one of the most dreaded complications of cirrhosis, is a frequent cancer with high mortality. Early primary liver cancer can be treated by surgery or ablation techniques, but advanced hepatocellular carcinoma remains a challenge for clinicians. Most of these patients have underlying cirrhosis, which complicates or even precludes treatment. Therefore, efficacious treatments without major side effects are welcomed. Initial results of treatment of advanced hepatocellular carcinoma with somatostatin analogues were promising, but subsequent trials have resulted in conflicting outcomes. This might be explained by different patient populations, differences in dosage and type of treatment and differences in somatostatin receptor expression in the tumor or surrounding tissue. It has been shown that the expression of somatostatin receptors in the tumor might be of importance to select patients who could benefit from treatment with somatostatin analogues. Moreover, somatostatin receptor expression in hepatocellular carcinoma has been shown to correlate with recurrence, prognosis, and survival. In this review, we will summarize the available data on treatment of primary liver cancer with somatostatin analogues and analyze the current knowledge of somatostatin receptor expression in hepatocellular carcinoma and its possible clinical impact.

Nuclear medicine techniques for the imaging and treatment of neuroendocrine tumours

2011 ◽  
Vol 18 (S1) ◽  
pp. S27-S51 ◽  
Author(s):  
Jaap J M Teunissen ◽  
Dik J Kwekkeboom ◽  
R Valkema ◽  
Eric P Krenning
Keyword(s):  
Nuclear Medicine ◽  
Neuroendocrine Tumours ◽  
Somatostatin Receptor ◽  
Somatostatin Analogues ◽  
Imaging Modalities ◽  
Tumour Regression ◽  
Receptor Subtypes ◽  
Receptor Imaging ◽  
Imaging Method ◽  
Somatostatin Receptor Subtypes

Nuclear medicine plays a pivotal role in the imaging and treatment of neuroendocrine tumours (NETs). Somatostatin receptor scintigraphy (SRS) with [111In-DTPA0]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 [90Y-DOTA0,Tyr3]octreotide and [177Lu-DOTA0,Tyr3]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 [177Lu-DOTA0,Tyr3]octreotate, a survival benefit of several years compared with historical controls has been reported.

scholarly journals Regulation of ghrelin secretion by somatostatin analogs in rats

2005 ◽  
Vol 152 (6) ◽  
pp. 887-894 ◽  
Author(s):  
Antonio P Silva ◽  
Kerstin Bethmann ◽  
Friedrich Raulf ◽  
Herbert A Schmid
Keyword(s):  
Plasma Levels ◽  
Acute Treatment ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Somatostatin Analogues ◽  
Receptor Expression ◽  
Overnight Fasting ◽  
Ghrelin Secretion ◽  
Fasted Rats ◽  
Low Expression

Objective: Ghrelin is a hormone present in the plasma in two forms: octanoylated and des-octanoylated ghrelin. In pathophysiological conditions such as Prader–Willi syndrome and ghrelinoma, elevated ghrelin plasma levels are associated with pathological obesity. Clinical studies have shown that somatostatin downregulates ghrelin plasma levels in healthy volunteers. The aim of this study was to investigate the effects of two somatostatin analogues, SOM230 and octreotide, on ghrelin secretion in rats. Methods: Ghrelin secretion was either unstimulated or stimulated by overnight fasting. Treatment with SOM230 and octreotide was either acute (s.c. injection 1 h before blood sampling) or prolonged (continuous s.c. infusion via 14-day osmotic minipumps). Results: Acute treatment with octreotide dose-dependently inhibited unstimulated and stimulated secretion of total and active ghrelin. SOM230 (30 μg/kg) inhibited active ghrelin in fasted rats. Lower doses had no effect. After 7 days of treatment, active ghrelin was strongly inhibited by both compounds in fasted animals, with a stronger effect for octreotide. Lower inhibition was achieved in fed rats. After 14 days, the inhibition with octreotide in fasted rats was lower and SOM230 had no effect. Somatostatin receptor expression analysis in the rat glandular stomach revealed a predominant sst1 and sst2 expression, low expression of sst3 and sst4, and hardly detectable sst5 mRNA expression. Conclusions: Somatostatin analogues may be useful for the inhibition of physiologically elevated ghrelin plasma levels. This inhibition appears to be mediated by sst2 receptors in the rat, and desensitizes after 14 days of treatment.

scholarly journals Survival in Patients with Neuroendocrine Tumours of the Small Intestine: Nomogram Validation and Predictors of Survival

2020 ◽  
Vol 9 (8) ◽  
pp. 2502
Author(s):  
Sonja Levy ◽  
Linde M. van Veenendaal ◽  
Catharina M. Korse ◽  
Emilie C.H. Breekveldt ◽  
Wieke H.M. Verbeek ◽  
...  
Keyword(s):  
Small Intestine ◽  
Neuroendocrine Tumours ◽  
Primary Tumour ◽  
Multivariable Analysis ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Risk Groups ◽  
Unknown Primary ◽  
Ki 67 ◽  
Unknown Primary Tumour

Neuroendocrine tumours of the small intestine (SI-NETs) are rare and heterogeneous. There is an unmet need for prognostication of disease course and to aid treatment strategies. A previously developed nomogram based on clinical and tumour characteristics aims to predict disease-specific survival (DSS) in patients with a SI-NET. We aimed to validate the nomogram and identify predictors of survival. Four hundred patients with a grade 1 or 2 SI-NET were included, between January 2000 and June 2016. Predicted 5- and 10-year survival was compared to actual DSS. Multivariable analysis identified predictors for actual DSS. We found that in low-, medium- and high-risk groups 5-year nomogram DSS vs. actual DSS was 0.86 vs. 0.82 (p < 0.001), 0.52 vs. 0.71 (p < 0.001) and 0.26 vs. 0.53 (p < 0.001), respectively. Ten-year nomogram DSS vs. actual DSS was 0.68 vs. 0.69 (p < 0.001), 0.40 vs. 0.50 (p < 0.001) and 0.20 vs. 0.35 (p < 0.001), respectively. Age, WHO-performance score of 2, Ki-67 index ≥10, unknown primary tumour, CgA > 6x ULN and elevated liver tests were identified as independent predictors for a worse DSS. This shows that the nomogram was able to differentiate, but underestimated DSS for patients with a SI-NET. Improvement of prognostication incorporating new emerging biomarkers is necessary to adequately estimate survival.

scholarly journals GEP–NETs UPDATE: Biotherapy for neuroendocrine tumours

2015 ◽  
Vol 172 (1) ◽  
pp. R31-R46 ◽  
Author(s):  
T Alonso-Gordoa ◽  
J Capdevila ◽  
E Grande
Keyword(s):  
Neuroendocrine Tumours ◽  
Symptomatic Relief ◽  
Somatostatin Receptors ◽  
Treatment Strategies ◽  
Mtor Inhibitors ◽  
Somatostatin Analogues ◽  
Antiangiogenic Agents ◽  
Tumour Control ◽  
Control Growth ◽  
Long Time

Neuroendocrine tumours (NETs) represent a less frequent and heterogeneous group of tumours, which has experienced, in recent years, a significant increase in effective therapeutic possibilities overcoming the disappointing results from chemotherapy. Initial improvements in treatment strategies came from somatostatin analogues (SSAs) that have widely demonstrated a significant improvement in symptomatic relief and tumour control growth by a complex mechanism of action over cell survival, angiogenesis and immunomodulation. Recent investigations have pointed out novel SSAs with a wider binding profile (pasireotide), chimeric molecules against somatostatin receptors and dopamine receptors and the combination with targeted agents, such as mTOR inhibitors or antiangiogenic agents. Immunotherapy is the second cornerstone in NET treatment and has been represented with interferon alpha for a long time, with a demonstrated activity on tumour and clinical response. Its less manageable adverse events have limited its usage. However, different checkpoints in immune system regulation have been effectively targeted in different solid tumours, and novel approaches are currently arising in NETs. In conclusion, biotherapy remains an active treatment strategy for initial approach in patients with NETs. Further investigation on patients' selection, molecular profiles, treatment sequence or combination and optimisation of current and novel biotherapy agents is required.

scholarly journals Well-differentiated gastroenteropancreatic G3 NET: findings from a large single centre cohort

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
K. Lithgow ◽  
H. Venkataraman ◽  
S. Hughes ◽  
H. Shah ◽  
J. Kemp-Blake ◽  
...  
Keyword(s):  
Primary Tumour ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Treatment Strategies ◽  
Biological Behavior ◽  
Queen Elizabeth Hospital ◽  
Neuroendocrine Neoplasms ◽  
Single Centre ◽  
Net G3 ◽  
Well Differentiated

AbstractNeuroendocrine neoplasms are known to have heterogeneous biological behavior. G3 neuroendocrine tumours (NET G3) are characterized by well-differentiated morphology and Ki67 > 20%. The prognosis of this disease is understood to be intermediate between NET G2 and neuroendocrine carcinoma (NEC). Clinical management of NET G3 is challenging due to limited data to inform treatment strategies. We describe clinical characteristics, treatment, and outcomes in a large single centre cohort of patients with gastroenteropancreatic NET G3. Data was reviewed from 26 cases managed at Queen Elizabeth Hospital, Birmingham, UK, from 2012 to 2019. Most commonly the site of the primary tumour was unknown and majority of cases with identifiable primaries originated in the GI tract. Majority of cases demonstrated somatostatin receptor avidity. Median Ki67 was 30%, and most cases had stage IV disease at diagnosis. Treatment options included surgery, somatostatin analogs (SSA), and chemotherapy with either platinum-based or temozolomide-based regimens. Estimated progression free survival was 4 months following initiation of SSA and 3 months following initiation of chemotherapy. Disease control was observed following treatment in 5/11 patients treated with chemotherapy. Estimated median survival was 19 months; estimated 1 year survival was 60% and estimated 2 year survival was 13%. NET G3 is a heterogeneous group of tumours and patients which commonly have advanced disease at presentation. Prognosis is typically poor, though select cases may respond to treatment with SSA and/or chemotherapy. Further study is needed to compare efficacy of different treatment strategies for this disease.

Detection rate of unknown primary tumour by using somatostatin receptor PET/CT in patients with metastatic neuroendocrine tumours: a meta-analysis

Endocrine ◽  
2019 ◽  
Vol 64 (3) ◽  
pp. 456-468 ◽  
Author(s):  
Sara De Dosso ◽  
Giorgio Treglia ◽  
Mariarosa Pascale ◽  
Adriana Tamburello ◽  
Prasanna Santhanam ◽  
...  
Keyword(s):  
Detection Rate ◽  
Neuroendocrine Tumours ◽  
Meta Analysis ◽  
Primary Tumour ◽  
Somatostatin Receptor ◽  
Unknown Primary ◽  
Unknown Primary Tumour ◽  
Pet Ct

scholarly journals Better way to image and manage Neuroendocrine Tumours: Role of 68Gallium DOTA-Peptide PET-CT scan

2018 ◽  
Vol 20 (2) ◽  
pp. 136
Author(s):  
Shankar Kumar Dey
Keyword(s):  
Molecular Imaging ◽  
Ct Scan ◽  
Significant Role ◽  
Neuroendocrine Tumours ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Pet Ct ◽  
Receptor Scintigraphy ◽  
Pet Ct Scan

<p>Neuroendocrine tumours (NETs) are special entity of neoplasms arising from nervous and endocrine systems and involving variety of organs. Over expression of somatostatin receptors is an unique characteristic of these tumours. This allows molecular imaging to play a significant role in evaluation of NETs using somatostatin analogues. <sup>111</sup> In Pentetreotide scintigraphy has been playing a significant role as molecular imaging of choice to locate the primary tumor, evaluate extent of disease and plan for surgical management. Recently <sup>68 </sup>Ga labelled peptides have emerged as promising PET tracers for scintigraphy of these tumours. Several recent studies have demonstrated the superiority of <sup>68</sup>Ga DOTA- Peptide PET-CT scan with a number of advantages over conventional somatostatin receptor scintigraphy.</p><p>Bangladesh J. Nuclear Med. 20(2): 136-142, July 2017</p>

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