Molecular Genomic Assessment Using a Blood-based mRNA Signature (NETest) is Cost-effective and Predicts Neuroendocrine Tumor Recurrence With 94% Accuracy

Modlin, Irvin M.; Kidd, Mark; Frilling, Andrea; Falconi, Massimo; Filosso, Pier Luigi; Malczewska, Anna; Kitz, Alexandra

doi:10.1097/sla.0000000000005026

Cited by 28 publications

(17 citation statements)

References 37 publications

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“…Follow-up of GEP-NENs requires frequent endoscopy with biopsy and/or CT scanning, which causes physical pain and radiation exposure, and is costly. In the US, using a follow-up strategy with NETest resulted in a 42% saving in cost [ 82 ]. NETest would also be effective in reducing these patients’ burdens.…”

Section: Biomarkersmentioning

confidence: 99%

Update on Epidemiology, Diagnosis, and Biomarkers in Gastroenteropancreatic Neuroendocrine Neoplasms

Takayanagi

Cho

Machida

et al. 2022

Cancers

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Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of malignancies that originate from the diffuse neuroendocrine cell system of the pancreas and gastrointestinal tract and have increasingly increased in number over the decades. GEP-NENs are roughly classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas; it is essential to understand the pathological classification according to the mitotic count and Ki67 proliferation index. In addition, with the advent of molecular-targeted drugs and somatostatin analogs and advances in endoscopic and surgical treatments, the multidisciplinary treatment of GEP-NENs has made great progress. In the management of GEP-NENs, accurate diagnosis is key for the proper selection among these diversified treatment methods. The evaluation of hormone-producing ability, diagnostic imaging, and histological diagnosis is central. Advances in the study of the genetic landscape have led to deeper understanding of tumor biology; it has also become possible to identify druggable mutations and predict therapeutic effects. Liquid biopsy, based on blood mRNA expression for GEP-NENs, has been developed, and is useful not only for early detection but also for assessing minimal residual disease after surgery and prediction of therapeutic effects. This review outlines the updates and future prospects of the epidemiology, diagnosis, and management of GEP-NENs.

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Section: Biomarkersmentioning

confidence: 99%

Update on Epidemiology, Diagnosis, and Biomarkers in Gastroenteropancreatic Neuroendocrine Neoplasms

Takayanagi

Cho

Machida

et al. 2022

Cancers

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“…In NENs, numerous transcriptomic studies have identified differentially expressed genes potentially related to tumorigenesis [ 29 – 31 ], while allowing to stratify NENs in new molecular subgroups, which may help to better understand their heterogeneity [ 32 ]. Moreover, efforts have been made to apply these discoveries to improve NEN diagnosis and prediction prognosis through specific tests such as the NETest [ 33 ], a gene expression assay developed to diagnose NENs based on PCR of blood-isolated RNA samples, which has evolved and is being tested to improve diagnosis and detect residual disease in NENs [ 34 , 35 ]. However, much remains to be known about the different types of RNA species and RNA-related biological processes in NENs.…”

Section: Rna Biology and Surveillancementioning

confidence: 99%

The uprise of RNA biology in neuroendocrine neoplasms: altered splicing and RNA species unveil translational opportunities

Blázquez‐Encinas

Moreno-Montilla

García-Vioque

et al. 2022

Rev Endocr Metab Disord

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Neuroendocrine neoplasms (NENs) comprise a highly heterogeneous group of tumors arising from the diffuse neuroendocrine system. NENs mainly originate in gastrointestinal, pancreatic, and pulmonary tissues, and despite being rare, show rising incidence. The molecular mechanisms underlying NEN development are still poorly understood, although recent studies are unveiling their genomic, epigenomic and transcriptomic landscapes. RNA was originally considered as an intermediary between DNA and protein. Today, compelling evidence underscores the regulatory relevance of RNA processing, while new RNA molecules emerge with key functional roles in core cell processes. Indeed, correct functioning of the interrelated complementary processes comprising RNA biology, its processing, transport, and surveillance, is essential to ensure adequate cell homeostasis, and its misfunction is related to cancer at multiple levels. This review is focused on the dysregulation of RNA biology in NENs. In particular, we survey alterations in the splicing process and available information implicating the main RNA species and processes in NENs pathology, including their role as biomarkers, and their functionality and targetability. Understanding how NENs precisely (mis)behave requires a profound knowledge at every layer of their heterogeneity, to help improve NEN management. RNA biology provides a wide spectrum of previously unexplored processes and molecules that open new avenues for NEN detection, classification and treatment. The current molecular biology era is rapidly evolving to facilitate a detailed comprehension of cancer biology and is enabling the arrival of personalized, predictive and precision medicine to rare tumors like NENs. Supplementary Information The online version contains supplementary material available at 10.1007/s11154-022-09771-4.

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“…Furthermore, future research should assess which selection criteria should be applied for induction PRRT. These could also include new potential prognostic factors for recurrence such as loss of ATRX/DAXX, ALT-positivity [49], and α-cell origin [50], as well as predictors of response to PRRT, such as the PRRT predictive quotient [51], or of recurrence, such as the NETest [52,53].…”

Section: Discussionmentioning

confidence: 99%

Induction therapy with 177Lu-DOTATATE procures long-term survival in locally advanced or oligometastatic pancreatic neuroendocrine neoplasm patients

Minczeles

Eijck

Gils

et al. 2022

Eur J Nucl Med Mol Imaging

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Purpose Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE induces objective response in up to 57% of pancreatic neuroendocrine neoplasms (panNENs). Therefore, PRRT may comprise a downstaging option for panNEN patients who are not eligible for upfront curative surgery or are at high risk for recurrence. The aim of this study was to assess the potency of induction PRRT for locally advanced panNENs and to evaluate the effect of surgery after PRRT on overall survival (OS). Methods Retrospective cohort study of panNEN patients treated with induction 177Lu-DOTATATE. Results After PRRT, 26 out of 49 patients underwent pancreatic surgery with curative intent (PRRT + surgery). Partial objective response was obtained in 62% of the PRRT + surgery group versus 26% of the patients not undergoing panNEN surgery (PRRT-only group, p = 0.02). Downstaging in tumour-vessel interface was observed in 38% of all patients with at least one involved vessel. Median OS was 14.7 years (95% CI 5.9–23.6) for the PRRT + surgery group compared to 5.5 years (95% CI 4.5–6.5) for the PRRT-only group (p = 0.003). In the Cox proportional hazards analysis, surgery was not significantly associated with OS after propensity score adjustment with cumulative activity, performance status, tumour size after PRRT, and tumour grade. Median progression-free survival was 5.3 years (95% CI 2.4–8.1) for the PRRT + surgery group and 3.0 years (95% CI 1.6–4.4) for the PRRT-only group (p = 0.02). Conclusion Early administration of PRRT followed by surgery is associated with favourable long-term outcomes in patients with locally advanced or oligometastatic panNEN and can be considered for selected patients with vascular involvement and/or increased risk of recurrence.

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Molecular Genomic Assessment Using a Blood-based mRNA Signature (NETest) is Cost-effective and Predicts Neuroendocrine Tumor Recurrence With 94% Accuracy

Abstract: Supplemental Digital Content is available in the text

Cited by 28 publications

References 37 publications

Update on Epidemiology, Diagnosis, and Biomarkers in Gastroenteropancreatic Neuroendocrine Neoplasms

Update on Epidemiology, Diagnosis, and Biomarkers in Gastroenteropancreatic Neuroendocrine Neoplasms

The uprise of RNA biology in neuroendocrine neoplasms: altered splicing and RNA species unveil translational opportunities

Induction therapy with 177Lu-DOTATATE procures long-term survival in locally advanced or oligometastatic pancreatic neuroendocrine neoplasm patients

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