Blood Molecular Genomic Analysis Predicts the Disease Course of Gastroenteropancreatic Neuroendocrine Tumor Patients: A Validation Study of the Predictive Value of the NETest®

Treijen, Mark J C van; Zee, Dennis van der; Heeres, Birthe C.; Staal, Femke C.R.; Vriens, Menno R.; Saveur, Lisette J.; Verbeek, Wieke H.M.; Korse, Catharina M.; Maas, Monique; Valk, Gerlof D.; Tesselaar, Margot E.T.

doi:10.1159/000509091

Cited by 24 publications

(22 citation statements)

References 37 publications

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“…As confirmation, 70% of patients with low tumor activity in the watchful waiting group and 64% of patients with low tumor activity in the treatment group had SD after 24 months. Finally, considering the 33 patients without evidence of disease at baseline, no patients with negative NETest (<20%) developed recurrence; moreover, the median value of NETest in patients who remain free of disease at follow-up was 27% compared to 53% in patients with recurrence [45].…”

Section: Resultsmentioning

confidence: 99%

NETest: A Systematic Review Focusing on the Prognostic and Predictive Role

et al. 2021

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The NETest is a standardized and reproducible liquid biopsy for neuroendocrine tumors (NETs). It evaluates the expression of 51 NET genes by real-time polymerase chain reaction, providing an accurate molecular profile of the neoplasm. Diagnostic utility of NETest has been widely demonstrated, while its role in predicting prognosis and treatment response is less studied. This systematic review aims to collect and discuss the available evidence on the prognostic and predictive role of NETest, trying to answer 3 questions, frequently raised in clinical practice. Is NETest able to differentiate stable from progressive disease? Increased NETest levels (at least >40%) correlate with disease progression. Is NETest able to predict tumor progression and tumor response to treatment? Some studies demonstrated that the baseline NETest score >33–40% could predict tumor progression. Moreover, NETest performed after treatment (as peptide receptor radionuclide therapy) could predict treatment response also before radiological findings, since the decrease or stability of NETest score predicts tumor response to treatment. Is NETest able to evaluate tumor recurrence risk after surgery? NETest can predict surgical treatment outcome detecting minimal residual disease after radical surgery, which is characterized by a lower but positive NETest score (20–40%), while a higher score (>33–40%) is associated with nonradical surgery. In conclusion, in addition to its demonstrated diagnostic role, this systematic review highlights the efficacy of NETest to assess disease status at the moment of the NETest execution and to predict tumor recurrence after surgery. The efficacy for other applications should be proven by additional studies.

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Section: Resultsmentioning

confidence: 99%

NETest: A Systematic Review Focusing on the Prognostic and Predictive Role

et al. 2021

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“…Others have discussed that a change of CgA (of 25-20%) might be a better prognostic predictor than a single measurement, however this needs further validation [47,48]. Currently, there is a debate on the prognostic potential of CgA, since even in patients with metastatic disease, CgA is often within the normal range [29]. This suggests there might be room for improvement to decide the optimal threshold.…”

Section: Discussionmentioning

confidence: 99%

“…Recent advances in identifying (molecular) prognostic factors and the development of liquid biopsies such as CTC, or circulating tumour transcripts (the NETest ® ), appear to be a valuable addition for individualized prognostication [31,54]. Prognostic studies often focussed either solely on clinical and tumour characteristics [3,4,7,10] or the sole predictive value of a biomarker alone (subsequently abandoning the use of clinical and tumour characteristics) [29,53,55]. Our study confirms the prognostic potential of a nomogram based on clinical and tumour characteristics while underlining the need for improvement.…”

Section: Discussionmentioning

confidence: 99%

“…In several malignancies, liquid biopsies were able to predict prognosis [25][26][27][28]. In neuroendocrine tumours, both CTC and circulating tumour transcripts showed promising results for monitoring disease [29][30][31]. For instance, the presence of ≥one CTC in blood samples of 178 patients with NETs was shown to be independently associated with worse overall-and progression-free survival [30].…”

Section: Introductionmentioning

confidence: 99%

“…For instance, the presence of ≥one CTC in blood samples of 178 patients with NETs was shown to be independently associated with worse overall-and progression-free survival [30]. In a recent study of 152 patients with GEP-NETs, circulating tumour transcripts (NETest ® ), using a cut-off of 33%, have been shown to be the strongest predictor for disease progression [29]. Yet, often in these studies the value of clinical and tumour characteristics is underappreciated.…”

Section: Introductionmentioning

confidence: 99%

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Survival in Patients with Neuroendocrine Tumours of the Small Intestine: Nomogram Validation and Predictors of Survival

Levy

Veenendaal

Korse

et al. 2020

JCM

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Neuroendocrine tumours of the small intestine (SI-NETs) are rare and heterogeneous. There is an unmet need for prognostication of disease course and to aid treatment strategies. A previously developed nomogram based on clinical and tumour characteristics aims to predict disease-specific survival (DSS) in patients with a SI-NET. We aimed to validate the nomogram and identify predictors of survival. Four hundred patients with a grade 1 or 2 SI-NET were included, between January 2000 and June 2016. Predicted 5- and 10-year survival was compared to actual DSS. Multivariable analysis identified predictors for actual DSS. We found that in low-, medium- and high-risk groups 5-year nomogram DSS vs. actual DSS was 0.86 vs. 0.82 (p < 0.001), 0.52 vs. 0.71 (p < 0.001) and 0.26 vs. 0.53 (p < 0.001), respectively. Ten-year nomogram DSS vs. actual DSS was 0.68 vs. 0.69 (p < 0.001), 0.40 vs. 0.50 (p < 0.001) and 0.20 vs. 0.35 (p < 0.001), respectively. Age, WHO-performance score of 2, Ki-67 index ≥10, unknown primary tumour, CgA > 6x ULN and elevated liver tests were identified as independent predictors for a worse DSS. This shows that the nomogram was able to differentiate, but underestimated DSS for patients with a SI-NET. Improvement of prognostication incorporating new emerging biomarkers is necessary to adequately estimate survival.

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Biomarkers to Inform Prognosis and Treatment for Unresectable or Metastatic GEP-NENs

Loree,

Chan,

Lim

et al. 2024

JAMA Oncol

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ImportanceEvidence-based treatment decisions for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) require individualized patient-centered decision-making that accounts for patient and cancer characteristics.ObjectiveTo create an accessible guidance document to educate clinicians and patients on biomarkers informing prognosis and treatment in unresectable or metastatic GEP-NENs.MethodsA multidisciplinary panel in-person workshop was convened to define methods. English language articles published from January 2016 to January 2023 in PubMed (MEDLINE) and relevant conference abstracts were reviewed to investigate prognostic and treatment-informing features in unresectable or metastatic GEP-NENs. Data from included studies were used to form evidence-based recommendations. Quality of evidence and strength of recommendations were determined using the Grading of Recommendations, Assessment, Development and Evaluations framework. Consensus was reached via electronic survey following a modified Delphi method.FindingsA total of 131 publications were identified, including 8 systematic reviews and meta-analyses, 6 randomized clinical trials, 29 prospective studies, and 88 retrospective cohort studies. After 2 rounds of surveys, 24 recommendations and 5 good clinical practice statements were developed, with full consensus among panelists. Recommendations focused on tumor and functional imaging characteristics, blood-based biomarkers, and carcinoid heart disease. A single strong recommendation was made for symptomatic carcinoid syndrome informing treatment in midgut neuroendocrine tumors. Conditional recommendations were made to use grade, morphology, primary site, and urinary 5-hydroxyindoleacetic levels to inform treatment. The guidance document was endorsed by the Commonwealth Neuroendocrine Tumour Collaboration and the North American Neuroendocrine Tumor Society.Conclusions and RelevanceThe study results suggest that select factors have sufficient evidence to inform care in GEP-NENs, but the evidence for most biomarkers is weak. This article may help guide management and identify gaps for future research to advance personalized medicine and improve outcomes for patients with GEP-NENs.

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Blood Molecular Genomic Analysis Predicts the Disease Course of Gastroenteropancreatic Neuroendocrine Tumor Patients: A Validation Study of the Predictive Value of the NETest®

Cited by 24 publications

References 37 publications

NETest: A Systematic Review Focusing on the Prognostic and Predictive Role

NETest: A Systematic Review Focusing on the Prognostic and Predictive Role

Survival in Patients with Neuroendocrine Tumours of the Small Intestine: Nomogram Validation and Predictors of Survival

Biomarkers to Inform Prognosis and Treatment for Unresectable or Metastatic GEP-NENs

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