Defining disease status in gastroenteropancreatic neuroendocrine tumors: Choi-criteria or RECIST?

Introduction Current monoanalyte biomarkers are ineffective in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). NETest, a novel multianalyte signature, provides molecular information relevant to disease biology. Aim(s) Independently validate NETest to diagnose GEP-NETs and identify progression in a tertiary referral center. Materials and methods Cohorts are 67 pancreatic NETs (PNETs), 44 small intestine NETs (SINETs) and 63 controls. Well-differentiated (WD) PNETs, n = 62, SINETs, all (n = 44). Disease extent assessment at blood draw: anatomical (n = 110) CT (n = 106), MRI (n = 7) and/or functional 68Ga-SSA-PET/CT (n = 69) or 18F-FDG-PET/CT (n = 8). Image-positive disease (IPD) was defined as either CT/MRI or 68Ga-SSA-PET/CT/18F-FDG-PET/CT-positive. Both CT/MRI and 68Ga-SSA-PET/CT negative diagnosis in WD-NETs was considered image-negative disease (IND). NETest (normal: 20): PCR (spotted plates). Data: mean ± SD. Results Diagnosis NETest was significantly increased in NETs (n = 111; 26 ± 21) vs controls (8 ± 4, p < 0.0001). Seventy-five (42 PNET, 33 SINET) were image positive. Eleven (8 PNET, 3 SINET; all WD) were IND. In IPD, NETest was significantly higher (36 ± 22) vs IND (8 ± 7, P < 0.0001). NETest accuracy, sensitivity and specificity are 97, 99 and 95%, respectively Concordance with imaging NETest was 92% (101/110) concordant with anatomical imaging, 94% (65/69) with 68Ga-SSA-PET/CT and 96% (65/68) dual modality (CT/MRI and 68Ga-SSA-PET/CT). In 70 CT/MRI positive, NETest was elevated in all (37 ± 22). In 40 CT/MRI negative, NETest was normal (11 ± 10) in 31. In 56 68Ga-SSA-PET/CT positive, NETest was elevated (36 ± 22) in 55. In 13 68Ga-SSA-PET/CT negative, NETest was normal (9 ± 8) in ten. Disease status NETest was significantly higher in progressive (61 ± 26; n = 11) vs stable disease (29 ± 14; n = 64; P < 0.0001) (RECIST 1.1). Conclusion NETest is an effective diagnostic for PNETs and SINETs. Elevated NETest is as effective as imaging in diagnosis and accurately identifies progression.

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Impact of Nutritional Status on Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) Aggressiveness

Nutrients ◽

10.3390/nu10121854 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1854 ◽

Cited By ~ 23

Author(s):

Luigi Barrea ◽

Barbara Altieri ◽

Giovanna Muscogiuri ◽

Daniela Laudisio ◽

Giuseppe Annunziata ◽

...

Keyword(s):

Nutritional Status ◽

Neuroendocrine Tumors ◽

Dietary Assessment ◽

Bioelectrical Impedance ◽

Disease Status ◽

Impedance Analysis ◽

Tumor Aggressiveness ◽

Anthropometric Parameters ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Cross Sectional

Neuroendocrine tumors (NETs) are rare neoplasms mostly originating from the gastroenteropancreatic tract (GEP-NETs). Data regarding nutritional status in GEP-NET patients are limited. The aim of the study was to investigate the nutritional status and adherence to the Mediterranean Diet (MD) in GEP-NET patients and to correlate them with tumor aggressiveness. A cross-sectional case-control observational study was conducted enrolling 83 patients with well-differentiated G1/G2 GEP-NETs after resection, as well as 83 healthy subjects, age, sex and body mass index-matched. Nutritional status was assessed by evaluating with Bioelectrical Impedance analysis and its phase angle (PhA), adherence to the MD according to PREDIMED score, dietary assessment, anthropometric parameters, and clinico-pathological characteristics. GEP-NET patients consumed less frequently vegetables, fruits, wine, fish/seafood, nuts, and more frequently red/processed meats, butter, cream, margarine, and soda drinks than controls. Patients with more aggressive disease presented a lower adherence to MD according to PREDIMED categories in comparison to G1, localized and free/stable disease status. A smaller PhA value and a lower PREDIMED score were significantly correlated with G2 tumor, metastases, and progressive disease. To the best of our knowledge, this is the first study reporting an association between nutritional status and tumor aggressiveness in a selected group of GEP-NETs. Moreover, higher intakes of food of MD, may represent a potential tool for prevention of tumor aggressiveness. Thus, a skilled nutritionist should be an integral part of the multidisciplinary management of GEP-NET patients.

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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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