NETest liquid biopsy is diagnostic of lung neuroendocrine tumors and identifies progressive disease

2018 ◽  
Author(s):  
Anna Malczewska ◽  
Beata Kos-Kudla ◽  
Pier-Luigi Filosso ◽  
Harry Aslanian ◽  
Anna Lewczuk ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Liquid Biopsy ◽  
Progressive Disease

scholarly journals Cardio-Metabolic Indices and Metabolic Syndrome as Predictors of Clinical Severity of Gastroenteropancreatic Neuroendocrine Tumors

2021 ◽  
Vol 12 ◽  
Author(s):  
Luigi Barrea ◽  
Giovanna Muscogiuri ◽  
Roberta Modica ◽  
Barbara Altieri ◽  
Gabriella Pugliese ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Liver ◽  
Neuroendocrine Tumors ◽  
Progressive Disease ◽  
Visceral Adiposity ◽  
Clinical Severity ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Alcoholic Fatty Liver ◽  
Cancer Data ◽  
Early Predictors

BackgroundObesity, mainly visceral obesity, and metabolic syndrome (MetS) are major risk factors for the development of type 2 diabetes, cardiovascular diseases, and cancer. Data analyzing the association of obesity and MetS with gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are lacking. Fatty liver index (FLI) is a non-invasive tool for identifying individuals with non-alcoholic fatty liver disease (NAFLD). Visceral adiposity index (VAI) has been suggested as a gender-specific indicator of adipose dysfunction. Both indexes have been proposed as early predictors of MetS. This study aimed to investigate the association of FLI VAI as early predictors of MetS with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).MethodsA cross-sectional, case–control, observational study was carried out at the ENETS Centers of Excellence Multidisciplinary Group for Neuroendocrine Tumors, University “Federico II”. VAI and FLI were calculated.ResultsWe enrolled 109 patients with histologically confirmed G1/G2 GEP-NET (53 M; 57.06 ± 15.96 years), as well as 109 healthy subjects, age, sex- and body mass index-matched. Forty-four GEP-NET patients were G2, of which 21 were with progressive disease, and 27 patients had metastases. GEP-NET patients had a higher value of VAI (p < 0.001) and FLI (p = 0.049) and higher MetS presence (p < 0.001) compared with controls. VAI and FLI values and MetS presence were higher in G2 than in G1 patients (p < 0.001), in patients with progressive disease, and in metastatic vs non-metastatic patients (p < 0.001). In addition, higher values of VAI and FLI and higher MetS presence were significantly correlated with the worst clinical severity of NENs. The cut-off values for the FLI and MetS to predict high grading of GEP-NETs and the presence of metastasis were also provided.ConclusionsThis is the first study investigating an association between VAI and FLI as early predictors of MetS and GEP-NET. Our findings report that the worsening of clinicopathological characteristics in GEP-NET is associated with higher presence of MetS, NAFLD, evaluated by FLI, and visceral adiposity dysfunction, evaluated by VAI. Addressing the clinical evaluation of MetS presence, NAFLD, and visceral adiposity dysfunction might be of crucial relevance to establish targeted preventive and treatment interventions of NEN-related metabolic comorbidities.

scholarly journals Chronotype: what role in the context of gastroenteropancreatic neuroendocrine tumors?

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Luigi Barrea ◽  
Giovanna Muscogiuri ◽  
Gabriella Pugliese ◽  
Roberta Modica ◽  
Daniela Laudisio ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Metabolic Profile ◽  
Progressive Disease ◽  
Biological Rhythms ◽  
Tumor Aggressiveness ◽  
Dark Cycle ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Pathological Characteristics ◽  
Increased Risk ◽  
The Subject

Abstract Background Chronotype is defined as a trait determining the subject circadian preference in behavioral and biological rhythms relative to external light–dark cycle. Although individual differences in chronotype have been associated with an increased risk of developing some types of cancer, no studies have been carried out in gastroenteropancreatic neuroendocrine tumors (GEP-NET). Materials We investigate the differences in chronotype between 109 GEP-NET and 109 healthy subjects, gender-, age-, and BMI-matched; and its correlation with tumor aggressiveness. Results GEP-NET patients have a lower chronotype score (p = 0.035) and a higher percentage of evening chronotype (p = 0.003) than controls. GEP-NET patients with morning chronotype had lower BMI, waist circumference, and higher percentage of MetS (p < 0.001) than evening type. Interestingly, considering the clinical pathological characteristics, patients with the presence of metastasis, grading G2, and in progressive disease presented the lower chronotype score (p = 0.004, p < 0.001, and p = 0.002; respectively) compared to other categories. Chronotype score was negatively associated with anthropometric measurements, metabolic profile, percentage of MetS, and Ki67 index (p < 0.001 for all). Conclusions GEP-NET patients have an unhealthy metabolic profile and present more commonly an evening chronotype. These results support the importance of including the assessment of chronotype in an adjunctive tool for the prevention of metabolic alterations and tumor aggressiveness of GEP-NET.

scholarly journals NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease

2019 ◽  
Vol 108 (3) ◽  
pp. 219-231 ◽  
Author(s):  
Anna Malczewska ◽  
Kjell Oberg ◽  
Lisa Bodei ◽  
Harry Aslanian ◽  
Anna Lewczuk ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Progressive Disease ◽  
Tumor Tissue ◽  
Disease Status ◽  
Large Cell ◽  
Clinical Progression ◽  
Lung Cancers ◽  
Recist 1.1 ◽  
Blinded Study ◽  
Matched Tissue

Background: There are no effective biomarkers for the management of bronchopulmonary carcinoids (BPC). We examined the utility of a neuroendocrine multigene transcript “liquid biopsy” (NETest) in BPC for diagnosis and monitoring of the disease status. Aim: To independently validate the utility of the NETest in diagnosis and management of BPC in a multicenter, multinational, blinded study. Material and Methods: The study cohorts assessed were BPC (n = 99), healthy controls (n = 102), other lung neoplasia (n = 101) including adenocarcinomas (ACC) (n = 41), squamous cell carcinomas (SCC) (n = 37), small-cell lung cancer (SCLC) (n = 16), large-cell neuroendocrine carcinoma (LCNEC) (n = 7), and idiopathic pulmonary fibrosis (IPF) (n = 50). BPC were histologically classified as typical (TC) (n = 62) and atypical carcinoids (AC) (n = 37). BPC disease status determination was based on imaging and RECIST 1.1. NETest diagnostic metrics and disease status accuracy were evaluated. The upper limit of normal (NETest) was 20. Twenty matched tissue-blood pairs were also evaluated. Data are means ± SD. Results: NETest levels were significantly increased in BPC (45 ± 25) versus controls (9 ± 8; p < 0.0001). The area under the ROC curve was 0.96 ± 0.01. Accuracy, sensitivity, and specificity were: 92, 84, and 100%. NETest was also elevated in SCLC (42 ± 32) and LCNEC (28 ± 7). NETest accurately distinguished progressive (61 ± 26) from stable disease (35.5 ± 18; p < 0.0001). In BPC, NETest levels were elevated in metastatic disease irrespective of histology (AC: p < 0.02; TC: p = 0.0006). In nonendocrine lung cancers, ACC (18 ± 21) and SCC (12 ± 11) and benign disease (IPF) (18 ± 25) levels were significantly lower compared to BPC level (p < 0.001). Significant correlations were evident between paired tumor and blood samples for BPC (R: 0.83, p < 0.0001) and SCLC (R: 0.68) but not for SCC and ACC (R: 0.25–0.31). Conclusions: Elevated ­NETest levels are indicative of lung neuroendocrine neoplasia. NETest levels correlate with tumor tissue and imaging and accurately define clinical progression.

scholarly journals Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study

2012 ◽  
Vol 19 (5) ◽  
pp. 657-666 ◽  
Author(s):  
Larry K Kvols ◽  
Kjell E Oberg ◽  
Thomas M O'Dorisio ◽  
Pharis Mohideen ◽  
Wouter W de Herder ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Carcinoid Syndrome ◽  
Progressive Disease ◽  
Symptom Control ◽  
Receptor Subtype ◽  
Open Label ◽  
Octreotide Lar ◽  
Common Drug ◽  
High Binding Affinity

Pasireotide (SOM230) is a novel multireceptor-targeted somatostatin (sst) analog with high binding affinity for sst receptor subtype 1, 2, 3 (sst1,2,3) and sst5. Because of this binding profile, pasireotide may offer symptom control in patients with neuroendocrine tumors (NETs) and carcinoid syndrome no longer responsive to octreotide LAR. This was a phase II, open-label, multicenter study of pasireotide in patients with advanced NET whose symptoms of carcinoid syndrome (diarrhea/flushing) were inadequately controlled by octreotide LAR. Patients received s.c. pasireotide 150 μg twice daily (bid), escalated to a maximum dose of 1200 μg bid until a clinical response was achieved. Forty-four patients were evaluated for efficacy and 45 for tolerability. Pasireotide 600–900 μg s.c. bid effectively controlled the symptoms of diarrhea and flushing in 27% of patients. Evaluation of tumor response in 23 patients showed 13 with stable disease and ten with progressive disease at study end. The most common drug-related adverse events were nausea (27%), abdominal pain (20%), weight loss (20%), and hyperglycemia (16%) and most were of mild or moderate severity. Pasireotide 600–900 μg s.c. bid was effective and generally well tolerated in controlling the symptoms of carcinoid syndrome in 27% of patients with advanced NET refractory or resistant to octreotide LAR therapy.

scholarly journals The NETest liquid biopsy is diagnostic for gastric neuroendocrine tumors: observations on the blood-based identification of microscopic and macroscopic residual disease

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
A. Malczewska ◽  
A. Procner ◽  
A. Walter ◽  
K. Kusnierz ◽  
W. Zajecki ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Liquid Biopsy ◽  
Residual Disease

scholarly journals The clinical applications of a multigene liquid biopsy (NETest) in neuroendocrine tumors

2020 ◽  
Vol 65 (1) ◽  
pp. 18-29 ◽  
Author(s):  
Anna Malczewska ◽  
Beata Kos-Kudła ◽  
Mark Kidd ◽  
Ignat Drozdov ◽  
Lisa Bodei ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Liquid Biopsy ◽  
Clinical Applications

A multi-transcript blood signature for detection and assessment of gut neuroendocrine tumors.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 216-216 ◽  
Author(s):  
Mark S. Kidd ◽  
Daniele Alaimo ◽  
Stephen Callahan ◽  
Nancy Smith Texeira ◽  
Ignat Drozdov ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Stable Disease ◽  
Treatment Efficacy ◽  
Progressive Disease ◽  
Performance Metrics ◽  
Treatment Options ◽  
High Sensitivity ◽  
Similar Efficacy ◽  
Metastatic Lesions

216 Background: Gut neuroendocrine tumors (NETs or “carcinoids”) are difficult to manage since they present with advanced disease and limited treatment options are available. Imaging is relatively insensitive in identifying treatment efficacy and the current biomarker, a neurosecretory peptide, Chromogranin A (CgA), has limited value. There is a lack of specific blood biomarker tests both to detect tumors and measure treatment responsiveness. We report the utility of a 51 marker peripheral blood signature (NETest) in comparison to CgA. Methods: The signature was validated using a 2-step qPCR method for detecting NETs in two sets (n=115; n=120) and for measuring treatment responses in a third set (n=133, including complete remission: n=4, clinically stable disease: n=82 and non-responders/clinically progressive disease: n=47). Comparison with CgA (DAKO-ELISA) was undertaken. The confounding effects of PPIs, age, sex and race were also determined for the PCR test. Results: The PCR NETest detected NETs with high sensitivity (85-98%) and specificity (93-97%). It identified pancreatic and gastrointestinal NETs with similar efficacy (>85%) as well as metastatic and non-metastatic lesions. NETest score was significantly reduced (p<0.004) following surgery or RFA and significantly higher in clinically progressive disease compared to stable disease (5.8±0.3 versus 0.6±0.1, p<0.002). The performance metrics for differentiating stable and progressive disease were sensitivity: 91% and specificity: 91%. The score was robust (reproducibility: Coefficient of Variation<2%).Long-term PPI use (>1yr), did not alter the NETest values, neither did age, sex or ethnicity. The PCR score was significantly (p<0.0005) more accurate than CgA for identifying NETs and was elevated in 91% of NETs when CgA was normal. Conclusions: This study demonstrates that a multi (51)-gene NET panel is both sensitive and specific for detecting NETs and is capable of differentiating clinically stable from progressive disease. The test is robust and significantly more sensitive and specific (accurate) than CgA. The NETest thus facilitates both accurate disease detection, and disease progress thereby permitting assessment of treatment efficacy.

Validation of the NETest liquid biopsy as a diagnostic for gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

2018 ◽  
Author(s):  
Anna Malczewska ◽  
Beata Kos-Kudla ◽  
Magdalena Witkowska ◽  
Agata Walter ◽  
Karolina Makulik ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Liquid Biopsy ◽  
Gastroenteropancreatic Neuroendocrine Tumors

scholarly journals 1252P Liquid biopsy to track KRAS G12C mutation at progressive disease in patients with advanced non-small cell lung cancer (NSCLC)

2021 ◽  
Vol 32 ◽  
pp. S983
Author(s):  
G. De Renzi ◽  
C. Nicolazzo ◽  
S. Pisegna ◽  
F. Belardinilli ◽  
I. Bottillo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Progressive Disease ◽  
Small Cell ◽  
Small Cell Lung

An Open-Label, Phase II Study Evaluating the Safety and Efficacy of PTK787/ZK222584 in Patients With Metastatic Neuroendocrine Tumors That Have Evidence of Progressive Disease or an Increase in Disease Related Syndrome Symptoms

Pancreas ◽  
2010 ◽  
Vol 39 (2) ◽  
pp. 271
Author(s):  
Lowell B. Anthony ◽  
Maria M. Chester ◽  
Bernard J. Brown ◽  
Stacy L. Michael ◽  
Jacky R. Seward ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Phase
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