Palliative resection of primary site in advanced gastroenteropancreatic neuroendocrine tumors improves survivals

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and abstruse neoplasms with increasing incidence and clinical relevance. The National Cancer Data Base was examined to identify GEP-NETcases from 2004 to 2013. In total, 39,454 patients diagnosed with GEP-NET were identified. Median age was 61 years. Majority was female (50.13%), white (79.49%), and had low-grade neoplasms (84.39%). On univariate analysis, age, sex, race, primary site, tumor size, and regional lymph node involvement were associated with tumor grade (P < 0.0001). On multivariate analysis, older age [odds ratio (OR) = 9.57], gender (male, OR = 1.29), and race continued to be associated with high-grade neoplasms. The primary site also remained a significant predictor of tumor grade. High-grade neoplasms were more likely to arise from the esophagus (OR = 317.75), hepatobiliary system (OR = 23.15), colorectum (OR = 14.37), ampulla of Vater (OR = 11.61), and stomach (OR = 7.84) compared with the appendix (OR = 5.41), pancreas (OR = 5.31), and small bowel (referent). The tumor grade for GEP-NETs is highly dependent on the primary site, suggesting different sites may be biologically distinct diseases. A personalized approach to GEP-NET treatment, tailored to the site of origin, is imperative.

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Tumour grade and primary site predict patterns of recurrence and survival in patients with resected gastroenteropancreatic neuroendocrine tumors

The American Journal of Surgery ◽

10.1016/j.amjsurg.2021.03.027 ◽

2021 ◽

Author(s):

Akie Watanabe ◽

Lily Yip ◽

Trevor D. Hamilton ◽

Jonathan M. Loree ◽

Heather C. Stuart

Keyword(s):

Neuroendocrine Tumors ◽

Primary Site ◽

Tumour Grade ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Patterns Of Recurrence

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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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