Identification of primary tumors in patients presenting with metastatic gastroenteropancreatic neuroendocrine tumors

The aim of this study was to explore the possible involvement of the angiopoietin (Ang)-1, -2/Tie-2 system in the development, growth, and metastases evolution of gastroenteropancreatic-neuroendocrine tumors (GEP-NETs). We prospectively examined the serum levels of Tie-2, Ang-1, and Ang-2 by ELISA in 42 patients with proven GEP-NETs and 27 controls. We also determined the expression of the Ang/Tie-2 system in freshly isolated peripheral blood monocytes and in tumor cells from malignant primary tumors and/or liver metastases samples from GEP-NET patients by flow cytometry and/or RT-PCR. Furthermore, the function of the Ang/Tie-2 system in monocytes from controls and patients was assessed by a chemotaxis assay. GEP-NET patients showed enhanced serum levels of soluble form of Tie-2 (sTie-2), Ang-1, and Ang-2 (P<0.05 in all cases), compared to controls. sTie-2 and Ang-2 levels were significantly higher in GEP-NETs with metastases compared to those with no metastases. In addition, a significant correlation was detected between Ang-2 levels and chromogranin A or sTie-2 concentrations or 5-hydroxy-indole acetic acid excretion (r=0.71, r=0.60, and r=0.81 respectively, P<0.01 in all cases). Furthermore, we observed an enhanced expression of Ang-1, Ang-2, and Tie-2 in freshly isolated tumor cells from GEP-NET both by immunohistochemistry and by RT-PCR. Interestingly, an enhanced expression and function of Tie-2 was detected in monocytes from GEP-NET patients. Our data suggest that the Ang/Tie-2 system is involved in the growth and development of metastases of GEP-NETs, and that favors the recruitment of Tie-2+ monocytes to the tumor site, where they can promote inflammation and angiogenesis.

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Localization of Neuroendrocrine Tumors Using Somatostatin Receptor Imaging with Indium-111-Pentetreotide (OctreoScan)

Cancer Control ◽

10.1177/107327489700400105 ◽

1997 ◽

Vol 4 (1) ◽

pp. 1-3 ◽

Cited By ~ 7

Author(s):

E. Christopher Ellison ◽

William J. Schirmer ◽

John O. Olsen ◽

Rodney V. Pozderac ◽

George Hinkle ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Imaging Techniques ◽

Somatostatin Receptor ◽

Somatostatin Receptors ◽

Receptor Imaging ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Primary Tumors ◽

Duodenal Tumor ◽

Computed Tomography Scanning ◽

Indium 111

Background Many imaging methods have been used to detect neuroendocrine tumors of the gastrointestinal system. There is no gold standard for identifying the location of primary tumors and their potential metastases, and most conventional imaging techniques cannot detect tumors less than 1.0 cm in size. Methods The authors have investigated the use of 111In-pentetreotide as an imaging agent for abdominal neuroendocrine tumors. Results The agent is cleared rapidly by the kidneys and is primarily excreted intact with a biologic half-life of six hours. The largest radiation burden is to the spleen and kidneys. A nine-center study conducted in Europe involved 365 patients with gastroenteropancreatic neuroendocrine tumors that were also imaged by other methods. The results of 111In-pentetreotide were in agreement with those obtained by other methods for 79% of tumor locations. An additional 110 tumor localizations were detected that were not seen with conventional methods. The smallest gastrinoma imaged by 111In-pentetreotide was a 4-mm duodenal tumor. Conclusions Scintigraphy with 111In-pentetreotide is effective in visualizing various somatostatin receptors characteristic of neuroendocrine tumors of the gastrointestinal tract. Insulinomas, however, are not well imaged. Concurrent computed tomography scanning is advised to minimize the risk of missing liver metastases.

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Gastroenteropancreatic neuroendocrine tumors: descriptive study in a reference Spanish hospital

Endocrine Abstracts ◽

10.1530/endoabs.32.p564 ◽

2013 ◽

Author(s):

Zayas Beatriz Leon de ◽

Olmo Garcia Maria Isabel del ◽

Agustin Ramos Prol ◽

Antonia Perez Lazaro ◽

Susana Tenes Rodrigo ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Descriptive Study ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Spanish Hospital

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Evaluation of neurofibromatosis type 1 and gastroenteropancreatic neuroendocrine tumors.

Endocrine Abstracts ◽

10.1530/endoabs.56.p138 ◽

2018 ◽

Author(s):

Juan Carlos Percovich ◽

Jose Atencia ◽

Rogelio Garcia ◽

Marcel Sambo ◽

Montserrat Blanco ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Gastroenteropancreatic Neuroendocrine Tumors

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Down-regulation of the Ataxia Telangiectasia Mutated Gene (ATM) is associated with increased metastatic potential and decreased overal survival in patients diagnosed with gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

Endocrine Abstracts ◽

10.1530/endoabs.63.p447 ◽

2019 ◽

Author(s):

Darko Katalinic ◽

Ivan Aleric ◽

Aleksandar Vcev ◽

Jure Mirat ◽

Lilly Soerensen ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Ataxia Telangiectasia ◽

Metastatic Potential ◽

Ataxia Telangiectasia Mutated ◽

Down Regulation ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Overal Survival

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The state of PRRT and its sequencing amongst current therapeutic options for gastroenteropancreatic neuroendocrine tumors

Neuroendocrinology ◽

10.1159/000516015 ◽

2021 ◽

Author(s):

Lauren M Raymond ◽

Tetiana Korzun ◽

Adel Kardosh ◽

Kenneth J. Kolbeck ◽

Rodney Pommier ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Standard Dose ◽

Peptide Receptor Radionuclide Therapy ◽

Somatostatin Analogues ◽

Tumor Burden ◽

Treatment Modalities ◽

Its Sequencing ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Reduce Tumor Burden ◽

Spectrum Of Patients

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common form of neuroendocrine neoplasia, but there is no current consensus for the sequencing of approved therapies, particularly with respect to peptide receptor radionuclide therapy (PRRT). This comprehensive review evaluates the data supporting approved therapies for GEP-NETs and recommendations for therapeutic sequencing with a focus on how PRRT currently fits within sequencing algorithms. The current recommendations for PRRT sequencing restrict its use to metastatic, inoperable, progressive midgut NETs, however, this may change with emerging data to suggest PRRT might be beneficial as neoadjuvant therapy for inoperable tumors, is more tolerable than other treatment modalities following first-line standard dose somatostatin analogues, and can be used as salvage therapy after disease relapse following prior successful cycles of PRRT. PRRT has also been shown to reduce tumor burden, improve quality of life, and prolong the time to disease progression in a broad spectrum of patients with GEP-NETs. As the various potential benefits of PRRT in GEP-NET therapy continues to expand, it is necessary to review and critically evaluate our treatment algorithms for GEP-NETs.

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Assessment of γ-H2AX and 53BP1 Foci in Peripheral Blood Lymphocytes to Predict Subclinical Hematotoxicity and Response in Somatostatin Receptor-Targeted Radionuclide Therapy for Advanced Gastroenteropancreatic Neuroendocrine Tumors

Cancers ◽

10.3390/cancers13071516 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1516

Author(s):

Thorsten Derlin ◽

Natalia Bogdanova ◽

Fiona Ohlendorf ◽

Dhanya Ramachandran ◽

Rudolf A. Werner ◽

...

Keyword(s):

Treatment Response ◽

Neuroendocrine Tumors ◽

Peripheral Blood ◽

Somatostatin Receptor ◽

Therapy Response ◽

Strand Break ◽

Peripheral Blood Lymphocytes ◽

Radioligand Therapy ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Blood Lymphocytes

Background: We aimed to characterize γ-H2AX and 53BP1 foci formation in patients receiving somatostatin receptor-targeted radioligand therapy, and explored its role for predicting treatment-related hematotoxicity, and treatment response. Methods: A prospective analysis of double-strand break (DSB) markers was performed in 21 patients with advanced gastroenteropancreatic neuroendocrine tumors. γ-H2AX and 53BP1 foci formation were evaluated in peripheral blood lymphocytes (PBLs) at baseline, +1 h and +24 h after administration of 7.4 GBq (177Lu)Lu-DOTA-TATE. Hematotoxicity was evaluated using standard hematology. Therapy response was assessed using (68Ga)Ga-DOTA-TATE PET/CT before enrollment and after 2 cycles of PRRT according to the volumetric modification of RECIST 1.1. Results: DSB marker kinetics were heterogeneous among patients. Subclinical hematotoxicity was associated with γ-H2AX and 53BP1 foci formation (e.g., change in platelet count vs change in γ-H2AX+ cells between baseline and +1 h (r = −0.6080; p = 0.0045). Patients showing early development of new metastases had less γ-H2AX (p = 0.0125) and less 53BP1 foci per cell at +1 h (p = 0.0289), and demonstrated a distinct kinetic pattern with an absence of DSB marker decrease at +24 h (γ-H2AX: p = 0.0025; 53BP1: p = 0.0008). Conclusions: Assessment of γ-H2AX and 53BP1 foci formation in PBLs of patients receiving radioligand therapy may hold promise for predicting subclinical hematotoxicity and early treatment response.

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