scholarly journals Gastrointestinal neuroendocrine tumors: a role for targeted therapies?

2007 ◽  
Vol 14 (2) ◽  
pp. 207-219 ◽  
Author(s):  
Matthew H Kulke
Keyword(s):  
Neuroendocrine Tumors ◽  
Tumor Regression ◽  
Somatostatin Analogs ◽  
Mammalian Target Of Rapamycin ◽  
Hepatic Metastases ◽  
Clinical Results ◽  
Interferon Α ◽  
Ablative Therapies ◽  
Surgical Debulking ◽  
Endothelial Growth Factor

Traditional therapies have offered patients with advanced gastrointestinal neuroendocrine tumors limited benefit. Selected patients with hepatic metastases may benefit from surgical debulking, embolization, or other ablative therapies. While somatostatin analogs are highly effective in controlling symptoms of hormonal secretion, they are only rarely associated with tumor regression. The clinical benefit associated with the administration of systemic agents such as interferon-α or cytotoxic chemotherapy is less clear, and the widespread use of such regimens has been limited by their relatively modest anti-tumor activity, as well as concerns regarding their potential toxicity. The mixed clinical results seen with these agents in neuroendocrine tumors have led to great interest in the development of novel treatment approaches for patients with advanced disease. Recent clinical studies of novel agents, particularly those targeting the vascular endothelial growth factor pathway and mammalian target of rapamycin, have demonstrated promising activity in patients with advanced neuroendocrine tumors. Ongoing randomized studies should help better define the role these and other targeted agents will play in the future treatment of patients with this disease.

Ablative therapies for liver metastases of digestive endocrine tumours.

2003 ◽  
pp. 463-468 ◽  
Author(s):  
D O'Toole ◽  
F Maire ◽  
P Ruszniewski
Keyword(s):  
Liver Metastases ◽  
Somatostatin Analogs ◽  
Hepatic Metastases ◽  
Vascular Occlusion ◽  
Treatment Method ◽  
Vascular Tumors ◽  
Endocrine Tumors ◽  
Hepatic Ischemia ◽  
Ablative Therapies

Hepatic metastases are frequently encountered in patients with digestive endocrine tumors and their presence plays an important role in quality of life and overall prognosis. Surgery is the treatment method of choice for hepatic metastases but this is frequently impossible due to the extent of disease. Systemic chemotherapy is offered to patients with diffuse and/or progressive liver metastases but results are disappointing especially in patients with metastases of midgut origin. In the latter patients with carcinoid syndrome, somatostatin analogs are frequently initially effective but their efficacy wanes due to disease progression and development of tachyphylaxis. Other therapeutic options in the treatment of hepatic metastases are locoregional strategies where vascular occlusion induces ischemia in these highly vascular tumors using either surgical or radiological techniques. Available methods include surgical ligation of the hepatic artery, transient hepatic ischemia or sequential hepatic arterialization. Trans-catheter arterial chemoembolization has proven effective in terms of long palliation and objective tumor responses. Other treatments aimed at regional destruction either alone or in combination with surgery include radiofrequency ablation and cryotherapy. The latter are usually important adjuncts to surgery and are usually reserved for limited disease.

scholarly journals Small Bowel and Colorectal Carcinoids

2018 ◽  
Vol 31 (05) ◽  
pp. 301-308 ◽  
Author(s):  
Raphael Byrne ◽  
Rodney Pommier
Keyword(s):  
Small Bowel ◽  
Neuroendocrine Tumors ◽  
Cytoreductive Surgery ◽  
Mammalian Target Of Rapamycin ◽  
Arterial Embolization ◽  
Angiogenesis Inhibitors ◽  
Somatostatin Analogues ◽  
Interferon Α ◽  
Peptide Receptor ◽  
Hepatic Arterial Embolization

AbstractNeuroendocrine tumors, or carcinoid tumors, of both the midgut and hindgut are quite rare, but their incidence is increasing. Surgery is the treatment of choice in patients who can tolerate an operation and have operable disease. Options for the treatment of metastatic disease include cytoreductive surgery, somatostatin analogues, interferon α, local liver therapies (hepatic arterial embolization, ablation), chemotherapy, Peptide-Receptor Radionucleotide Radiotherapy, angiogenesis inhibitors, and mammalian target of rapamycin inhibitors.

scholarly journals Treatment of Liver Metastases in Patients with Neuroendocrine Tumors of Gastroesophageal and Pancreatic Origin

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ping Gu ◽  
Jennifer Wu ◽  
Elliot Newman ◽  
Franco Muggia
Keyword(s):  
Liver Metastasis ◽  
Neuroendocrine Tumors ◽  
Somatostatin Analogs ◽  
Hepatic Metastases ◽  
Progression Free Survival ◽  
Therapeutic Options ◽  
Free Survival ◽  
Octreotide Lar ◽  
Pancreatic Net ◽  
Pancreatic Origin

Well-to-moderately differentiated neuroendocrine tumors of gastroesophageal and pancreatic origin (GEP-NETs) with liver metastasis are a heterogeneous group of malignancies for which a range of therapeutic options have been employed. Surgical resection of hepatic metastases or hepatic artery embolization may be beneficial in patients with hepatic-predominant metastatic disease. Patients with “carcinoid” syndrome and syndromes associated with functional pancreatic NET (PNET) can be effectively treated with somatostatin analogs. On the other hand, the efficacy of systemic chemotherapy for these patients is limited. A placebo-controlled, double-blind, prospective, and randomized study showed that octreotide LAR improves progression-free survival in patients with advanced midgut functional “carcinoids.” In patients with advanced pancreatic NET, randomized, placebo-controlled studies have recently demonstrated that treatment with the tyrosine kinase inhibitor sunitinib or with mTOR inhibitor everolimus is associated with improved progression-free survival. Based on these studies, octreotide LAR, sunitinib, or everolimus are now considered as first-line therapeutic options in patients with advanced NET. Future studies will likely further define the role of these agents in patients with carcinoid liver metastasis and pancreatic NET liver metastasis.

scholarly journals Somatostatin receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors

2010 ◽  
Vol 17 (1) ◽  
pp. R53-R73 ◽  
Author(s):  
Dik J Kwekkeboom ◽  
Boen L Kam ◽  
Martijn van Essen ◽  
Jaap J M Teunissen ◽  
Casper H J van Eijck ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Pet Imaging ◽  
Tumor Regression ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Receptor Subtype ◽  
Receptor Imaging ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Pet Tracer ◽  
First Choice

Somatostatin receptor imaging (SRI) with [111In-DTPA0]octreotide has proven its role in the diagnosis and staging of gastroenteropancreatic neuroendocrine tumors (GEPNETs). Newer radiolabeled somatostatin analogs which can be used in positron emission tomography (PET) imaging, and which have a higher affinity for the somatostatin receptor, especially receptor subtype-2, have been developed. It would be desirable, however, if one radiolabeled analog became the new standard for PET imaging, because the current application of a multitude of analogs implies a fragmented knowledge on the interpretation of the images that are obtained in clinical practice. In our view, the most likely candidates for such a universal PET tracer for SRI are [68Ga-DOTA0,Tyr3]octreotate or [68Ga-DOTA0,Tyr3]octreotide. Treatment with radiolabeled somatostatin analogs is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumors. Symptomatic improvement may occur with all 111In-, 90Y-, or 177Lu-labeled somatostatin analogs that have been used for peptide receptor radionuclide therapy (PRRT). The results that were obtained with [90Y-DOTA0,Tyr3]octreotide and [177Lu-DOTA0,Tyr3]octreotate are very encouraging in terms of tumor regression. Also, if kidney protective agents are used, the side effects of this therapy are few and mild, and the median duration of the therapy response for these radiopharmaceuticals is 30 and 40 months respectively. The patients' self-assessed quality of life increases significantly after treatment with [177Lu-DOTA0,Tyr3]octreotate. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with [177Lu-DOTA0,Tyr3]octreotate. These data compare favorably with the limited number of alternative treatment approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable GEPNETs.

Gynecologic Cancer InterGroup (GCIG) Consensus Review for Carcinoid Tumors of the Ovary

2014 ◽  
Vol 24 (Supp 3) ◽  
pp. S35-S41 ◽  
Author(s):  
Nicholas Simon Reed ◽  
Eva Gomez-Garcia ◽  
Dolores Gallardo-Rincon ◽  
Brigitte Barrette ◽  
Klaus Baumann ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Case Reports ◽  
Gynecologic Cancer ◽  
Somatostatin Analogs ◽  
Mammalian Target Of Rapamycin ◽  
International Studies ◽  
New Developments ◽  
Small Series ◽  
Localized Disease ◽  
Level I

AbstractNeuroendocrine tumors (NETs) are a heterogeneous group of neoplasms most commonly occurring in the gastrointestinal tract or the lungs. More frequent are gastrointestinal tumors, but over the past 30 years, there have been a number of small series or anecdotal case reports on ovarian NETs. Neuroendocrine tumors in the gynecologic tract are uncommon and account for about 2% of all gynecologic malignancies but may also be metastatic from other sites. They require a multimodality therapeutic approach determined by the extent of disease and the primary organ of involvement. Pathological diagnosis is critical to guide therapy. Surgery is the cornerstone of treatment for localized disease. There have been many new developments for treatment of advanced NETs including somatostatin analogs, hepatic artery embolization, chemotherapy, interferons, mammalian target of rapamycin inhibitors and radiolabeled somatostatin analogs. Given the rarity and lack of level I evidence, this is by nature more of a guidance and recommendation for management of these rare tumors until we can mount international studies.

scholarly journals Treatments for patients with advanced neuroendocrine tumors: a network meta-analysis

2019 ◽  
Vol 11 ◽  
pp. 175883591985367 ◽  
Author(s):  
Tingting Liu ◽  
Jiehao Liao ◽  
Jun Dang ◽  
Guang Li
Keyword(s):  
Neuroendocrine Tumors ◽  
Meta Analysis ◽  
Somatostatin Analogs ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Interferon Α ◽  
Serious Adverse Events ◽  
Scientific Meetings ◽  
Well Differentiated

Background: It remains unknown which is the most effective regimen among the available therapies for advanced well-differentiated neuroendocrine tumors (NETs). We performed a network meta-analysis to address this important issue. Methods: PubMed, Embase, Web of Science, Cochrane Library, and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Progression-free survival (PFS) data was the primary outcome of interest, and overall survival (OS) and serious adverse events (SAEs) were the secondary outcomes of interests, reported as hazard ratio (HR), or odds ratio (OR) and 95% confidence intervals (CIs). Results: Included in the meta-analysis were 21 eligible articles reporting 15 RCTs with a total of 2922 patients randomized to receive 11 treatments. Peptide receptor radionuclide therapy (PRRT) showed significant PFS advantage over somatostatin analogs (SSA) (HR = 0.21, 95% CI: 0.11–0.41), everolimus (HR = 0.25, 95% CI: 0.11–0.53), sunitinib (HR = 0.29, 95% CI: 0.10–0.82), everolimus+SSA (HR = 0.26, 95% CI: 0.12–0.54), and everolimus+bevacizumab (HR = 0.31, 95% CI: 0.11–0.82). OS findings were not significantly different between treatments. In terms of treatment rankings of PFS, PRRT had the highest probability (96%) of being the most effective treatment, followed by SSA+bevacizumab (86%) and SSA+interferon-α (IFN-α) (78%). As for toxicity, risk of SAEs was similar between the three treatments. Based on the benefit–risk ratio, PRRT, SSA+bevacizumab, and SSA+IFN-α seemed to be the best, second-, and third-best treatment, respectively. Conclusions: PRRT is likely to be the most preferable treatment for patients with advanced well-differentiated NETs. SSA+bevacizumab and SSA+IFN-α also seem to be more effective regimens with limited risk of SAEs.

Long-term outcome after transarterial chemoembolization of hepatic metastases from neuroendocrine tumors

2013 ◽  
Author(s):  
Sanja Ognjanovic ◽  
Milan Petakov ◽  
Tatjana Isailovic ◽  
Valentina Elezovic ◽  
Djuro Macut ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Transarterial Chemoembolization ◽  
Hepatic Metastases ◽  
Term Outcome ◽  
Long Term Outcome

scholarly journals Mammalian target of rapamycin signaling activation patterns in neuroendocrine tumors of the lung

2010 ◽  
Vol 17 (4) ◽  
pp. 977-987 ◽  
Author(s):  
Luisella Righi ◽  
Marco Volante ◽  
Ida Rapa ◽  
Veronica Tavaglione ◽  
Frediano Inzani ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Differential Sensitivity ◽  
Initiation Factor ◽  
Target Of Rapamycin ◽  
Low Grade ◽  
Mtor Inhibition ◽  
Signaling Activation ◽  
Activation Status

Among alternative therapeutic strategies in clinically aggressive neuroendocrine tumors (NETs) of the lung, promising results have been obtained in experimental clinical trials with mammalian target of rapamycin (mTOR) inhibitors, though in the absence of a proven mTOR signaling activation status. This study analyzed the expression of phosphorylated mTOR (p-mTOR) and its major targets, the ribosomal p70S6-kinase (S6K) and the eukaryotic initiation factor 4E-binding protein 1 (4EBP1) in a large series of 218 surgically resected, malignant lung NETs, including 24 metastasizing typical carcinoids, 73 atypical carcinoids, 60 large cell neuroendocrine carcinomas (LCNECs), and 61 small cell carcinomas (SCLCs). By immunohistochemistry, low-to-intermediate-grade tumors as compared with high-grade tumors showed higher levels of p-mTOR and phosphorylated S6K (p-S6K) (P<0.001), at variance with phosphorylated 4EBP1 (p-4EBP1), which was mainly expressed in LCNECs and SCLCs (P<0.001). The activated status of mTOR pathway was proved by the strong correlation of p-mTOR with p-S6K and somatostatin receptor(s). Western blot analysis of NET tumor samples confirmed such findings, and differential sensitivity to mTOR inhibition according to mTOR pathway activation characteristics was determined in two lung carcinoid cell lines in vitro. None of the investigated molecules had an impact on survival. However, in low-grade tumors, low p-mTOR expression correlated with lymph node metastases (P=0.016), recurrent disease, and survival (P=0.005). In conclusion, these data demonstrate a differential mTOR activation status in the spectrum of pulmonary NETs, possibly suggesting that mTOR pathway profiling might play a predictive role in candidate patients for mTOR-targeted therapies.

Treatment experience of hepatic metastases from neuroendocrine tumors using transarterial chemoembolization

2020 ◽  
pp. 109-111
Author(s):  
V.S. Trifanov ◽  
E.N. Kolesnikov ◽  
A.V. Snezhko ◽  
M.N. Chernyak ◽  
A.L. Bazaev ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Transarterial Chemoembolization ◽  
Hepatic Metastases ◽  
Treatment Experience
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