The Quest for Circulating Biomarkers in Neuroendocrine Neoplasms: a Clinical Perspective

Mariën, Laura; Islam, Odeta; Chhajlani, Siddharth; Lybaert, Willem; Peeters, Marc; Van Camp, Guy; Op de Beeck, Ken; Vandamme, Timon

doi:10.1007/s11864-023-01147-3

Cited by 4 publications

(3 citation statements)

References 107 publications

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“…In addition, drugs such as diazepam and phenobarbital may lead to a false-positive result [ 67 ]. Moreover, false positives can be observed due to malabsorption and celiac disease, while renal insufficiency can, in turn, lead to false negatives [ 68 ]. False-negative results have also been reported in patients on medications such as levodopa, methyldopa, acetylsalicylic acid, adrenocorticotrophic hormone (ACTH), and phenothiazines.…”

Section: Specific Circulating Hormonesmentioning

confidence: 99%

“…False-negative results have also been reported in patients on medications such as levodopa, methyldopa, acetylsalicylic acid, adrenocorticotrophic hormone (ACTH), and phenothiazines. 5-HIAA showed a high specificity of ∼100% but low sensitivity (~35%) due to diverse expression in individuals [ 68 ].…”

Section: Specific Circulating Hormonesmentioning

confidence: 99%

“…The majority of VIPomas are located in the pancreas (75%), and patients can present with VIP-producing neuroblastoma, ganglioneuroblastoma, ganglioneuroma, pheochromocytoma, and paraganglioma, or neoplasms of the retroperitoneum and mediastinum [ 81 ]. Assessment of VIP levels is often sufficient to diagnose a patient with VIPoma since elevated VIP levels (>60 pmol/L) achieve a specificity of 100% [ 68 ].…”

Section: Specific Circulating Hormonesmentioning

confidence: 99%

See 2 more Smart Citations

Biochemical Markers for Neuroendocrine Tumors: Traditional Circulating Markers and Recent Development—A Comprehensive Review

Franchina,

Cavalcoli,

Falco

et al. 2024

Diagnostics

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Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms presenting unique challenges in diagnosis and management. Traditional markers such as chromogranin A (CgA), pancreatic polypeptide (PP), and neuron-specific enolase (NSE) have limitations in terms of specificity and sensitivity. Specific circulating markers such as serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and various gastrointestinal hormones such as gastrin, glucagon, somatostatin, and vasoactive intestinal peptide (VIP) have a role in identifying functional NENs. Recent advances in molecular and biochemical markers, also accounting for novel genomic and proteomic markers, have significantly improved the landscape for the diagnosis and monitoring of NENs. This review discusses these developments, focusing on both traditional markers such as CgA and NSE, as well as specific hormones like gastrin, insulin, somatostatin, glucagon, and VIP. Additionally, it covers emerging genomic and proteomic markers that are shaping current research. The clinical applicability of these markers is highlighted, and their role in improving diagnostic accuracy, predicting surgical outcomes, and monitoring response to treatment is demonstrated. The review also highlights the need for further research, including validation of these markers in larger studies, development of standardized assays, and integration with imaging techniques. The evolving field of biochemical markers holds promise for improving patient outcomes in the treatment of NENs, although challenges in standardization and validation remain.

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Section: Specific Circulating Hormonesmentioning

confidence: 99%

Section: Specific Circulating Hormonesmentioning

confidence: 99%

Section: Specific Circulating Hormonesmentioning

confidence: 99%

See 1 more Smart Citation

Biochemical Markers for Neuroendocrine Tumors: Traditional Circulating Markers and Recent Development—A Comprehensive Review

Franchina,

Cavalcoli,

Falco

et al. 2024

Diagnostics

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Improvements and future perspective in diagnostic tools for neuroendocrine neoplasms

Massironi,

Franchina,

Ippolito

et al. 2024

Expert Review of Endocrinology & Metabolism

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NETest in advanced high‐grade gastroenteropancreatic neuroendocrine neoplasms

Sorbye,

Hjortland,

Vestermark

et al. 2024

J Neuroendocrinology

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Molecular blood biomarkers are lacking for high‐grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN). To histologically distinguish between neuroendocrine carcinoma (NEC), neuroendocrine tumors G3 (NET G3), adenocarcinoma and MINEN is often challenging. The mRNA‐based NETest has diagnostic, prognostic and predictive value in neuroendocrine tumors G1‐2 but has not been studied in HG GEP‐NEN. Patients with advanced HG GEP‐NEN were prospectively included in an observational study. A blood sample was collected before the start of chemotherapy and pseudonymised before NETest was performed. NETest results are expressed as an activity index (NETest score) from 0 to 100. The normal score cut‐off is 20. Histological sections were pseudonymised before centralized pathological re‐evaluation. Samples from 60 patients were evaluable with the NETest. Main primary tumor sites were colon (14), rectum (12), pancreas (11) and esophagus (7). Re‐classification: 30 NEC, 12 NET G3, 3 HG‐NEN ambiguous morphology, 8 MiNEN, 3 adenocarcinomas with neuroendocrine differentiation (ADNE), 3 adenocarcinomas and 1 NET G2. Elevated NETest (>20) was seen in 38/45 (84%) HG GEP‐NEN, all 17 large‐cell NEC (100%), 11/13 (85%) small‐cell NEC, all ambiguous cases and 7/12 (64%) NET G3. NETest was elevated in 5/8 (63%) MiNEN, 2/3 ADNE, however not in 3 adenocarcinomas. Median survival was 10.2 months (9.6–10.8 95%CI) for evaluable HG GEP‐NEN treated with palliative chemotherapy (n = 39), and survival was significantly shorter in patients with NETest >60 with an OS of only 6.5 months. This is the first study to evaluate use of the NETest in advanced HG GEP‐NEN. The NETest was almost always elevated in GEP‐NEC and in all large‐cell NEC. The NETest was also frequently elevated in NET G3 and MiNEN, however cases were limited. Baseline NETest was not predictive for benefit of chemotherapy, however a NETest >60 was prognostic with a shorter survival for patients receiving chemotherapy.

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The Quest for Circulating Biomarkers in Neuroendocrine Neoplasms: a Clinical Perspective

Cited by 4 publications

References 107 publications

Biochemical Markers for Neuroendocrine Tumors: Traditional Circulating Markers and Recent Development—A Comprehensive Review

Biochemical Markers for Neuroendocrine Tumors: Traditional Circulating Markers and Recent Development—A Comprehensive Review

Improvements and future perspective in diagnostic tools for neuroendocrine neoplasms

NETest in advanced high‐grade gastroenteropancreatic neuroendocrine neoplasms

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