scholarly journals Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues

2005 ◽  
Vol 12 (4) ◽  
pp. 683-699 ◽  
Author(s):  
G A Kaltsas ◽  
D Papadogias ◽  
P Makras ◽  
A B Grossman
Keyword(s):  
Neuroendocrine Tumours ◽  
Performance Status ◽  
Somatostatin Receptors ◽  
Tumour Response ◽  
Somatostatin Analogues ◽  
Symptomatic Improvement ◽  
Tumour Regression ◽  
Somatostatin Analogue ◽  
Tumour Mass ◽  
Pancreatic Islet Cell

Neuroendocrine tumours (NETs) constitute a heterogeneous group of tumours that frequently express cell membrane-specific peptide receptors, such as somatostatin receptors (SSTRs), and of which gastroenteropancreatic (GEP), carcinoid and pancreatic islet cell tumours exhibit the highest expression of SSTRs. Radiolabelled receptor-binding somatostatin analogues (octreotide and lanreotide) act as vehicles to guide radioactivity to tissues expressing SSTRs, and can thus be used for their diagnosis and treatment. After the localization of NETs bearing SSTRs with 111In-octreotide (OctreoScan), a number of radioisotopes with different physical properties have been used for their treatment. The administration of high doses of the Auger electron and γ-emitter 111In-diethylenetriaminepenta-acetic acid (DTPA)0,octreotide in patients with metastatic tumours has been associated with considerable symptomatic improvement but relatively few and short-lived objective tumour responses. The use of another radiolabelled somatostatin analogue coupled with 90Y, a pure β-emitter, 90Y-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA)0,Tyr3,octreotide (90Y-DOTATOC, OctreoTher), was associated with 10–30% objective tumour response rates, and appears to be particularly effective in larger tumours. 111In- and 90Y-DOTA-lanreotide has also been used for the treatment of NETs although its therapeutic efficacy is probably inferior to that of octreotide-based radiopharmaceuticals. More recently, treatment with 177Lu-DOTA0,Tyr3octreotate (177Lu-DOTATATE), which has a higher affinity for the SSTR subtype 2, resulted in approximately 30% complete or partial tumour responses; this radiopharmaceutical is particularly effective in smaller tumours. Furthermore, treatment using both 90Y-DOTATOC and 177Lu-DOTA0,Tyr3octreotate seems promising, as the combination of these radiopharmaceuticals could be effective in tumours bearing both small and large lesions. Tumour regression is positively correlated with a high level of uptake on 111In-octreotide scintigraphy, limited tumour mass and good performance status. In general, better responses have been obtained in GEP tumours than other NETs. The side effects of this form of therapy are relatively few and mild, particularly when kidney-protective agents are used. Treatment with radiolabelled somatostatin analogues presents a promising tool for the management of patients with inoperable or disseminated NETs, and particularly GEP tumours.

scholarly journals Unresectable Recurrent Multiple Meningioma: A Case Report with Radiological Response to Somatostatin Analogues

2016 ◽  
Vol 9 (2) ◽  
pp. 520-525 ◽  
Author(s):  
Ana Ortolá Buigues ◽  
Irene Crespo Hernández ◽  
Manuela Jorquera Moya ◽  
Jose Ángel Díaz Pérez
Keyword(s):  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Somatostatin Analogue ◽  
Continuous Administration ◽  
Antiangiogenic Effect ◽  
Neurological Improvement ◽  
Radiological Response ◽  
Multiple Meningioma ◽  
Multiple Recurrences

Medical treatment of meningiomas is reserved for cases in which surgery and radiotherapy have failed. Given that a high percentage of meningiomas express somatostatin receptors, treatment with somatostatin analogues has been proposed. In addition, these medications have been shown to have an antiproliferative and antiangiogenic effect in vitro. To date, very few cases with clinical response and none with radiological response have been described. The case described here is the first to report a radiological response. A 76-year-old Caucasian male was first diagnosed with unresectable meningioma at age 47. The patient experienced multiple recurrences and underwent three surgeries and radiotherapy over the years from the initial diagnosis. Despite treatment, the disease continued its progression. Based on an Octreoscan positive for tumour uptake, therapy with extended-release somatostatin analogues was started. Although no clinical neurological improvement was observed, magnetic resonance imaging scans revealed a discreet but continuous radiological response over time. After >2 years of continuous administration of lanreotide, the patient remains progression free. In highly selected cases, somatostatin analogue treatment for meningioma may be beneficial. Based on our findings, treatment with somatostatin analogues should be maintained longer than previously described before evaluating treatment response.

[111In-DTPA-D-Phe1]Octreotide scintigraphy in patients with carcinoid tumours: the predictive value for somatostatin analogue treatment

1994 ◽  
Vol 131 (6) ◽  
pp. 577-581 ◽  
Author(s):  
Eva Tiensuu Janson ◽  
Jan-Erik Westlin ◽  
Barbro Eriksson ◽  
Håkan Ahlström ◽  
Sten Nilsson ◽  
...  
Keyword(s):  
Predictive Value ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
University Hospital ◽  
Somatostatin Analogue ◽  
Carcinoid Tumours ◽  
Malignant Carcinoid ◽  
Receptor Scintigraphy ◽  
Octreotide Scintigraphy

Tiensuu Janson E, Westlin J-E, Eriksson B, Ahlström H, Nilsson S, Öberg K. [111In-DTPA-D-Phe1]Octrotide scintigraphy in patients with carcinoid tumours: the predictive value for somatostatin analogue treatment. Eur J Endocrinol 1994:131:577–81. ISSN 0804–4643 This study was performed to evaluate whether the presence or absence of somatostatin receptors in malignant carcinoid tumours detected by [111In-DTPA-D-Phe1]octreotide scintigraphy can be used to predict response to somatostatin analogue treatment. Thirty patients were investigated, 28 with midgut carcinoid tumours and two with foregut carcinoid tumours. Twenty-seven patients showed pathological uptake in tumour lesions at scintigraphy: of these, 22 responded to somatostatin analogue treatment using octreotide, somatuline or octastatin, while five patients failed to respond. None of the three patients displaying negative scintigraphic investigations responded to treatment with somatostatin analogues. These results show a good correlation between the somatostatin receptor status and the patients' ability to respond to somatostatin analogue treatment (p = 0.014). We conclude that somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]octreotide can be used to select patients with malignant carcinoid tumours suitable for somatostatin analogue treatment and exclude those that will not benefit from such medication. Eva Tiensuu Janson, Dept of Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden

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 Antitumour Effects of Somatostatin Analogues in the Treatment of Neuroendocrine Tumours

2012 ◽  
Vol 08 (03) ◽  
pp. 156
Author(s):  
Diogo Assed Bastos ◽  
Brenda Gumz ◽  
Frederico Costa ◽  
◽  
◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Antitumour Activity ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Antiangiogenic Activity ◽  
Tumour Shrinkage ◽  
Phosphotyrosine Phosphatases ◽  
Antitumour Effects

Neuroendocrine tumours (NETs) are rare and heterogeneous neoplasms that can present with functional syndromes due to the hypersecretion of peptides. Somatostatin analogues (SSAs) have been used since the 1980s for the treatment of neuroendocrine tumours, with the aim of controlling the symptoms of functioning tumours and improving patients’ quality of life. Data from preclinical studies offer evidence of both direct and indirect mechanisms by which SSAs can exert antitumour effects. The activation of somatostatin receptors by SSAs leads to the activation of phosphotyrosine phosphatases, which control downstream apoptotic and antiproliferation signalling pathways. Also, the suppression of secretion of several growth factors and inhibition of antiangiogenic activity by SSAs indirectly inhibits tumour cell proliferationin vitro. Previous uncontrolled studies had shown tumour shrinkage and disappearance in response to the SSA octreotide. Recent results from the randomised and placebo-controlled PROMID trial have demonstrated that octreotide has antitumour activity in patients with metastatic mid-gut NETs. This article examines recent data providing evidence of the antitumour activity of somatostatin analogues.

Resistant Paediatric Somatotropinomas due to AIP Mutations: Role of Pegvisomant

2018 ◽  
Vol 90 (3) ◽  
pp. 196-202 ◽  
Author(s):  
Kriti Joshi ◽  
Adrian F. Daly ◽  
Albert Beckers ◽  
Margaret Zacharin
Keyword(s):  
Combined Therapy ◽  
Somatostatin Analogues ◽  
Somatostatin Analogue ◽  
Tumour Mass ◽  
Residual Tumour ◽  
Control Disease ◽  
Long Acting ◽  
Analogue Octreotide

Background: Somatotropinomas are rare in childhood and frequently associated with genetic mutations. AIP mutations are found in 20–25% cases and cause aggressive somatotropinomas, often resistant to somatostatin analogues. Aims: To assess responses to multimodal therapy including pegvisomant in 2 children with sporadic somatotropinomas due to AIP mutations. Case Description: We report 2 children, a boy aged 13 and a girl aged 10, with rapid growth, visual impairment, and growth hormone hypersecretion. Magnetic resonance imaging confirmed a pituitary macroadenoma with parasellar extension in both. Despite multiple surgical attempts to debulk tumour mass, residual tumour persisted. Genetic analysis showed two different AIP mutations (patient 1: c.562delC [p.Arg188Glyfs*8]; patient 2: c.140_ 163del24 [p.Gly47_Arg54del8]). They were initially treated with a long-acting somatostatin analogue (octreotide LAR 30 mg/month) and cabergoline as a dopamine agonist, with the later addition of pegvisomant titrated up to 20 mg/day and with radiotherapy for long-term control. Somatostatin analogue was ceased due to patient intolerance and lack of control. Patient 1 had normalization of insulin-like growth factor-1 (IGF-1) after 5 months of combined therapy with pegvisomant and cabergoline. For patient 2, normalization of IGF-1 was achieved after 2 months of cabergoline and pegvisomant. Conclusion: AIP-associated tumours can be resistant to management with somatostatin analogues. Pegvisomant can safely be used, to normalize IGF-1 levels and help control disease.

Antitumour Effects of Somatostatin Analogues in the Treatment of Neuroendocrine Tumours

2010 ◽  
Vol 8 (2) ◽  
pp. 94
Author(s):  
Diogo Assed Bastos ◽  
Brenda Gumz ◽  
Frederico Costa ◽  
◽  
◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Antitumour Activity ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Antiangiogenic Activity ◽  
Tumour Shrinkage ◽  
Phosphotyrosine Phosphatases ◽  
Antitumour Effects

Neuroendocrine tumours (NETs) are rare and heterogeneous neoplasms that can present with functional syndromes due to the hypersecretion of peptides. Somatostatin analogues (SSAs) have been used since the 1980s for the treatment of neuroendocrine tumours, with the aim of controlling the symptoms of functioning tumours and improving patients’ quality of life. Data from preclinical studies offer evidence of both direct and indirect mechanisms by which SSAs can exert antitumour effects. The activation of somatostatin receptors by SSAs leads to the activation of phosphotyrosine phosphatases, which control downstream apoptotic and antiproliferation signalling pathways. Also, the suppression of secretion of several growth factors and inhibition of antiangiogenic activity by SSAs indirectly inhibits tumour cell proliferationin vitro. Previous uncontrolled studies had shown tumour shrinkage and disappearance in response to the SSA octreotide. Recent results from the randomised and placebo-controlled PROMID trial have demonstrated that octreotide has antitumour activity in patients with metastatic mid-gut NETs. This article examines recent data providing evidence of the antitumour activity of somatostatin analogues.

Impact of VEGF and CgA as new predictive tools in management of elderly hormone-refractory prostate cancer (HRPC) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16070-e16070
Author(s):  
I. Carreca ◽  
F. Bellomo ◽  
S. Burgio ◽  
P. D'Alia ◽  
D. Piazza ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Response ◽  
Clinical Benefit ◽  
Tumour Response ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Biochemical Response ◽  
Somatostatin Analogue ◽  
Hormone Refractory ◽  
Pre Treatment

e16070 Background: Prostate cancer is one of the most frequent malignancy in men of the Western countries. The identification of new predictive factors of drug activity is crucial for elderly cancer patients, who need a particular selection according to prediction of efficacy and safety by pre-treatment parameters. Several prostate cancers show focal neuroendocrine (NE) spots and CgA seems to be associated to NE phenotype both in tissue and in circulation. VEGF expression in NE cells is corelated with clinical characteristics and disease-specific survival. Somatostatin analogues induce a decrease in plasma CgA and could have also anti-angiogenic activity by inhibition of VEGF, bFGF and GH/IGF-I axis. Methods: elderly patients, median age 75 (range: 65–83), were selected for hormone-refractory disease, previously treated with CAB. Serum PSA and plasmatic CgA and VEGF were evaluated in all pts at baseline (T0) and at 4 months (T4) and 8 months (T8) after therapy. Pts were treated with docetaxel 75 mg/m2 every 3 weeks for 6 cycles and octreotide acetate 20 mg administered intramuscularly every 4 weeks until progression. Clinical and biochemical response, progression- free survival and toxicity were also evaluated. A correlation of basal CgA and VEGF with biochemical response, clinical response and clinical benefit was also investigated. Results: Median duration of follow-up was 18 months (range: 8–32). Patients evaluable for response were 22. PSA response rate (RR) was observed in 10/22 (45%); clinical objective RR was 33% (7/22). Clinical benefit was observed in 19/22 pts (86%). Only mild toxicities was observed in both groups. CgA and VEGF were both strongly reduced after therapy. Lower CgA values correlated with clinical benefit, lower VEGF values also correlated with biochemical and clinical response. Conclusions: This combination treatment showed a good toxicity profile. The most relevant data in this study refer to the role of serum CgA and VEGF levels, for prediction of tumour response. If these findings were confirmed, it could be sufficient to measure these markers levels for identification of those HRPC patients who have more probability of obtaining clinical benefit from a docetaxel-based treatment in combination with a somatostatin analogue. No significant financial relationships to disclose.

Sixty-eight consecutive cases of neuroendocrine tumor treated with somatostatin analogues: A 20-year single-center experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14707-e14707
Author(s):  
Theodoros Savvoukidis ◽  
Silke Cameron ◽  
Giuliano Ramadori
Keyword(s):  
Small Bowel ◽  
Neuroendocrine Tumours ◽  
Somatostatin Analogues ◽  
Observation Time ◽  
The Body ◽  
Tumour Mass ◽  
Good Tolerability ◽  
Single Center Experience ◽  
Duration Of Response ◽  
Long Acting

e14707 Background: Neuroendocrine tumours (NET) arise from enterochromaffine and related cells found in epithelial organs throughout the body. Hormone related symptoms in neuroendocrine tumours are well treated with somatostatin analogues. Previous experience has demonstrated some antiproliferative activity of somatostatin analogues in the treatment of NET. Methods: In the last 20 years 68 patients with histologically proven NET were treated: primaries in small bowel (27), pancreas (17), rectum (9), appendix (5), lung (4), unknown (3), extra- adrenal abdominal paragangliomas (2) and stomach (1). The mean age of first diagnosis was 56 years. All of them received somatostatin analogues in long acting depot administration (or combination interferon/somatostatin analogues) for a minimum period of two months and a maximum of 139 months. Somatostatin therapy was started in patients with endocrine-active tumours immediately after the diagnosis and in patients with endocrine-inactive tumours after an observation time of 3 months without therapy if progress was observed. Tumor size was assessed every 3 months after begin of therapy. Results: Best responses were a stable disease in 46 of 68 patients (68%) and a partial remission in 2 (3%). Twenty of 68 patients (29%) showed progress. The responses achieved were in small bowel 20/27; pancreas 14/17; rectum 7/9; appendix 4/5 and lung 3/4. The median duration of response was 34 months. Conclusions: Our results document that treatment with somatostatin analogues prolongs time to progression in NET. Stabilisation of tumour mass itself is a relevant outcome for patients with NET. The benefit of somatostin analogues is indipendent to use of chemotherapy. Because of its efficacy and the good tolerability somatostatin analogues can be considered a first line treatment option.

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 Recent advances in radiological and radionuclide imaging and therapy of neuroendocrine tumours

2004 ◽  
Vol 151 (1) ◽  
pp. 15-27 ◽  
Author(s):  
G Kaltsas ◽  
A Rockall ◽  
D Papadogias ◽  
R Reznek ◽  
AB Grossman
Keyword(s):  
Chromaffin Cell ◽  
Neuroendocrine Tumours ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Therapeutic Modality ◽  
Response To Treatment ◽  
Helical Computed Tomography ◽  
Positron Emission ◽  
Octreotide Therapy ◽  
Magnetic Resonance Imaging Mri

Neuroendocrine tumours (NETs) constitute a heterogeneous group of tumours that are able to express cell membrane neuroamine uptake mechanisms and/or specific receptors, such as somatostatin receptors, which can be of great value in the localization and treatment of these tumours. Scintigraphy with (111)In-pentetreotide has become one of the most important imaging investigations in the initial identification and staging of gastro-enteropancreatic (GEP) tumours, whereas helical computed tomography (CT), magnetic resonance imaging (MRI), endoscopic and/or peri-operative ultrasonography are used for the precise localization of GEPs and in monitoring their response to treatment. Scintigraphy with (123)I-MIBG (meta-iodobenzylguanidine) is sensitive in the identification of chromaffin cell tumours, although scintigraphy with (111)In-pentetreotide may also have a role in the localization of malignant chromaffin cell tumours and medullary thyroid carcinoma; for further localization and monitoring of the response to treatment both CT and MRI are used with high diagnostic accuracy. More recently, positron emission tomography (PET) scanning is being increasingly used for the localization of NETs, particularly when other imaging modalities have failed, although its precise role and utility remain to be defined. Surgery is still the usual initial therapeutic, and only curative, modality of choice; however, the majority of NETs will require further treatment with somatostatin analogues and/or interferon; chemotherapy may be used for progressive and highly aggressive NETs, but its role has not been clearly defined. For those NETs that demonstrate uptake to a diagnostic scan with (123)I-MIBG or (111)In-octreotide, therapy with radionuclides such as (131)I-MIBG or (111)In/(90)Y-octreotide or other isotopes, presents a further evolving therapeutic modality.

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