Blood Transcript Profiling for the Detection of Neuroendocrine Tumors: Results of a Large Independent Validation Study

Treijen, Mark J C van; Korse, Catharina M.; Leeuwaarde, Rachel S van; Saveur, Lisette J.; Vriens, Menno R.; Verbeek, Wieke H.M.; Tesselaar, Margot E. T.; Valk, Gerlof D.

doi:10.3389/fendo.2018.00740

Cited by 51 publications

(48 citation statements)

References 45 publications

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“…The NETest was 93% positive, whereas single analytes were positive in ∼40%. In 2 other independent studies, a daily clinical practice registry audit (NCT02270567) of NEN [102] and a prospective, university-based study [100] the diagnostic accuracy of the NETest was confirmed to be 95-100%. Physician confidence in using monoanalytes like CgA or pancreastatin was low (accuracy 25-50%).…”

Section: T -Primary Tumourmentioning

confidence: 91%

“…The values are standardised, reproducible and are not influenced by age, gender, ethnicity, fasting or acid suppressive medication [98,99]. The assay has been independently validated [100]. Since the multigene assay captures diverse functional "omic" components of each tumour, the assay provides a broad molecular biological characterisation of tumour behaviour.…”

Section: T -Primary Tumourmentioning

confidence: 99%

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Neuroendocrine Neoplasms of the Small Bowel and Pancreas

et al. 2019

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The traditionally promulgated perspectives of neuroendocrine neoplasms (NEN) as rare, indolent tumours are blunt and have been outdated for the last 2 decades. Clear increments in their incidence over the past decades render them increasingly clinically relevant, and at initial diagnosis many present with nodal and/or distant metastases (notably hepatic). The molecular pathogenesis of these tumours is increasingly yet incompletely understood. Those arising from the small bowel (SB) or pancreas typically occur sporadically; the latter may occur within the context of hereditary tumour predisposition syndromes. NENs can also be associated with endocrinopathy of hormonal hypersecretion. Tangible advances in the development of novel biomarkers, functional imaging modalities and therapy are especially applicable to this sub-set of tumours. The management of SB and pancreatic neuroendocrine tumours (NET) may be challenging, and often comprises a multidisciplinary approach wherein surgical, medical, interventional radiological and radiotherapeu-tic modalities are implemented. This review provides a comprehensive overview of the epidemiology, pathophysiology, diagnosis and treatment of SB and pancreatic NETs. Moreover, we provide an outlook of the future in these tumour types which will include the development of precision oncology frameworks for individualised therapy, multi-analyte predictive biomarkers, artificial intelligence-derived clinical decision support tools and elucidation of the role of the microbiome in NEN development and clinical behaviour.According to SEER version 18, SBNEN and PanNEN incidences are currently estimated at 1.2 and 0.7 per 100,000, respectively [5]. The overall 20-year duration prevalence of all NEN is estimated at 171,321; SBNEN constituting 32,122 patients with 3-fold fewer PanNEN (10,707) [5]. Possible attributable factors for this increase evolving epidemiology include increased use of endoscopy and also improvements in the sensitivity of widely used imaging modalities, leading to increased detection of early-stage, asymptomatic disease [5].The median overall survival (OS) for NEN (irrespective of site and grade) is 9.3 years [5]. For SB (median OS: 14 years), this ranges from 70 months (advanced disease with distant metastases) to 170 months (localised disease) and from 30 months (Grade 3) to 160 months (Grade 1). For pancreas (median OS: 3.6 years): 21 months (advanced) to 235 months (localised disease) and from 15 months (Grade 3) to 140 months (Grade 1) [5].Multivariable analyses have identified that ethnicity, age, differentiation, stage and site all have statistically significant correlations with survival. In general, Caucasian ethnicity, age (< 50 years) and localised, well-differentiated NEN exhibit the best survival. SB tumour patients are approximately 1.5 times more likely to survive longer than those with PanNEN [19]. Many of these correlations are self-evident since they pertain to degree of malignancy, disease duration and patient performance status.OS (median 5-year) app...

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Section: T -Primary Tumourmentioning

confidence: 91%

Section: T -Primary Tumourmentioning

confidence: 99%

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

et al. 2019

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“…Gene expression data are used in the calculation of the NETest score, ranging from 0 to 100 that reflects disease activity. The ULN is 20 [20], scores of 20-40 are associated with low disease activity, 41-79 represent intermediate disease activity and ≥80 reflect high disease activity ( Fig. 1a) [17].…”

Section: Patient Demographics and Follow-upmentioning

confidence: 99%

Evaluation of circulating transcript analysis (NETest) in small intestinal neuroendocrine neoplasms after surgical resection

et al. 2020

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Purpose Surgical resection is the only effective curative strategy for small intestinal neuroendocrine neoplasms (SINENs). Nevertheless, the evaluation of residual disease and prediction of disease recurrence/progression remains a problematic issue. Methods We evaluated 13 SINENs that underwent surgical resection of the primary tumour and/or mesenteric mass. Patients were divided in three groups: (a) Group 1: SINENs that underwent resection with curative intent, (b) Group 2: SINENs treated with resection in the setting of metastatic disease, which remained stable and (c) Group 3: SINENs treated with resection in the setting of metastatic disease, with evidence of any progression at follow-up. NETest and chromogranin A were measured pre-operatively and post-operatively during a 22-month median follow-up period and compared with imaging studies. NETest score <20% was determined as normal, 20-40% low, 41-79% intermediate and ≥80% high score.Results NETest score was raised in all (100%) SINENs pre-operatively. Surgery with curative intent resulted in NETest score reduction from 78.25 ± 15.32 to 25.25 ± 1.75 (p < 0.05). Low NETest scores post-operatively were evident in all cases without clinical evidence of residual disease (Group 1). However, the low disease activity score suggested the presence of microscopic residual disease. In three cases (75%) with stable disease (Group 2) the NETest score was low consistent with indolent disease. In the progressive disease group (Group 3), a high NETest score was present in three cases (60%) and an intermediate NETest score in the remainder (40%). Conclusions Blood NETest scores accurately identified SINENs and were significantly decreased by curative surgery. Monitoring NETest post-operatively may facilitate management by identifying the presence of residual/progressive disease.

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“…42,43 The NETest™ has also been reported to be able to differentiate stable from progressive sporadic gastro-pancreatic NETs and may have the potential to predict prognosis 44 42,43 The NETest™ has also been reported to be able to differentiate stable from progressive sporadic gastro-pancreatic NETs and may have the potential to predict prognosis 44 …”

Section: How Us Eful Are Current B I Omark Er S At Pred Ic Ting Thementioning

confidence: 99%

“…Recently, the NETest™, a multitranscript molecular signature for PCR-based blood analysis, has been developed as a biomarker with independent studies reporting variable diagnostic performance in its ability to detect sporadic gastro-pancreatic NETs. 42,43 The NETest™ has also been reported to be able to differentiate stable from progressive sporadic gastro-pancreatic NETs and may have the potential to predict prognosis 44 ; however, additional studies are required to truly establish the clinical utility of the NETest™ in the non-MEN-1 setting. To date, in patients with MEN-1, there are no published data regarding the performance of the NETest™ in the context of MEN1-associated NF-pNETs.…”

Section: How Us Eful Are Current B I Omark Er S At Pred Ic Ting Thementioning

confidence: 99%

What is the appropriate management of nonfunctioning pancreatic neuroendocrine tumours disclosed on screening in adult patients with multiple endocrine neoplasia type 1?

Challis

Casey

Grossman

et al. 2019

Clinical Endocrinology

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Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumour syndrome characterised by a predisposition to the development of endocrine tumours of the parathyroid glands, pituitary and pancreas: 30%-80% of patients with MEN1 develop pancreatic neuroendocrine tumours (pNETs), with metastatic tumours and/or their sequelae contributing to increased morbidity and early mortality. The optimal management of nonfunctioning (NF) pNETs in MEN1 remains controversial. Whilst pancreatic resection is widely recommended for tumours >2 cm, for smaller tumours (≤2 cm) a well-established consensus guiding the indications for surgical intervention does not exist. Although total pancreatectomy may be curative for some patients, both short-and long-term complications make this an unsatisfactory option for many patients. For small (<2 cm) MEN1 NF-pNETs, some clinicians advocate surveillance based largely on retrospective data that suggest 50%-80% of these lesions are stable over time and infrequently exhibit accelerated growth rates. It is increasingly recognised, however, that NF-pNETs exhibit unpredictable malignant behaviour that is not determined by tumour size alone, thereby prompting other clinicians to advocate surgery for all MEN1 NF-pNETs, irrespective of size. Such uncertainty poses clinical management challenges with regards to the timing and extent of surgery, which is further hindered by the inability to stratify patients based on predicted tumour behaviour. It is therefore critical that future MEN1 research initiatives include: (a) the discovery of biomarkers that better predict tumour behaviour; (b) the evaluation of medical therapies that may delay, or even prevent, the need for pancreatic surgery;and, ultimately, (c) improvement in the quality of life for individuals with MEN1. Here, based on the published literature, we address the Clinical Question, 'What is the management of NF-pNETs disclosed on screening in adult patients with MEN1?'.

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Blood Transcript Profiling for the Detection of Neuroendocrine Tumors: Results of a Large Independent Validation Study

Cited by 51 publications

References 45 publications

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

Evaluation of circulating transcript analysis (NETest) in small intestinal neuroendocrine neoplasms after surgical resection

What is the appropriate management of nonfunctioning pancreatic neuroendocrine tumours disclosed on screening in adult patients with multiple endocrine neoplasia type 1?

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