Circulating Transcript Analysis (NETest) in GEP-NETs Treated With Somatostatin Analogs Defines Therapy

Ćwikła, Jarosław B.; Bodei, Lisa; Kolasińska-Ćwikła, Agnieszka; Sankowski, A; Modlin, Irvin M.; Kidd, Mark

doi:10.1210/jc.2015-2792

Cited by 111 publications

(117 citation statements)

References 39 publications

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“…Regarding the follow-up phase, recent prospective studies (Cwikla et al 2015, Pavel et al 2017a show that circulating CgA does not represent a valid marker of morphological evolution of disease and has therefore no utility in this setting.…”

Section: Discussionmentioning

confidence: 99%

“…More definite evidence about this issue has emerged in the last 2 years, with 2 prospective reports demonstrating the poor capability of CgA changes in reflecting morphological behavior of NENs. In 2015, Cwikla et al (2015) prospectively analyzed a cohort of 28 non-cured gastroenteropancreatic NENs treated with somatostatin analogues (SSA). Considering an at least 25% increase as cut-off, authors found low concordance, namely 64%, between CgA modifications and tumor slope.…”

Section: Assessment Of Morphological Evolution In Patients With Non-cmentioning

confidence: 99%

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Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

Marotta

Zatelli

Sciammarella³

et al. 2018

Endocrine-Related Cancer

125

104

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Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up and definition of treatment strategy. This review is focused on chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by (a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; (b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA-secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects.

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Section: Discussionmentioning

confidence: 99%

Section: Assessment Of Morphological Evolution In Patients With Non-cmentioning

confidence: 99%

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

Marotta

Zatelli

Sciammarella³

et al. 2018

Endocrine-Related Cancer

125

104

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“…Multianalyte algorithm analysis strategies based upon a 51-gene signature (NETest) have been reported in NETs [24,26,28,29,51,52,53]. This defines the circulating NET ‘fingerprint' [54] and exhibits a higher sensitivity and specificity (98 and 97%, respectively) than secretory markers for identifying neoplasia [25,51].…”

Section: Discussionmentioning

confidence: 99%

“…Details of the PCR methodology, mathematical analysis and validation have been published in detail [24,26,28,29]. The procedure utilizes a 2-step protocol (RNA isolation, cDNA production and PCR) [24,28] from EDTA-collected whole blood [24,28].…”

Section: Methodsmentioning

confidence: 99%

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NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive

et al. 2016

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Background/Aims: A key issue in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is early identification and prediction of disease progression. Clinical evaluation and imaging are limited due to the lack of sensitivity and disease indolence. We assessed the NETest as a predictive and prognostic marker of progression in a long-term follow-up study. Methods: GEP-NETs (n = 34) followed for a median 4 years (2.2-5.4) were evaluated. WHO tumor grade/stage grade 1: n = 17, grade 2: n = 14, grade 3: n = 1 (for 2, no grade was available); 31 (91%) were stage IV. Baseline and longitudinal imaging and blood biomarkers were available in all, and progression was defined per standard clinical protocols (RECIST 1.0). The NETest was measured by quantitative PCR of blood and multianalyte algorithmic analysis (disease activity scaled 0-100% with low <40% and high activity risk cutoffs >80%); chromogranin A (CgA) was measured by radioimmunoassay (normal <150 µg/l); progression-free survival (PFS) was analyzed by Cox proportional-hazard regression and Kaplan-Meier analysis. Results: At baseline, 100% were NETest positive, and CgA was elevated in 50%. The only baseline variable (Cox modeling) associated with PFS was NETest (hazard ratio = 1.022, 95% confidence interval = 1.005-1.04; p < 0.012). Using Kaplan-Meier analyses, the baseline NETest (>80%) was significantly associated (p = 0.01) with disease progression (median PFS 0.68 vs. 2.78 years with <40% levels). The NETest was more informative (96%) than CgA changes (>25%) in consistently predicting disease alterations (40%, p < 2 × 10^-5, χ² = 18). The NETest had an earlier time point change than imaging (1.02 ± 0.15 years). Baseline NETest levels >40% in stable disease were 100% prognostic of disease progression versus CgA (χ² = 5, p < 0.03). Baseline NETest values <40% accurately (100%) predicted stability over 5 years (p = 0.05, χ² = 3.8 vs. CgA). Conclusion: The NETest correlated with a well-differentiated GEP-NET clinical status. The NETest has predictive and prognostic utility for GEP-NETs identifying clinically actionable alterations ∼1 year before image-based evidence of progression.

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Measurement of circulating transcript levels (NETest) to detect disease recurrence and improve follow‐up after curative surgical resection of well‐differentiated pancreatic neuroendocrine tumors

Genc

Jilesen

Dijkum

et al. 2018

Journal of Surgical Oncology

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Circulating Transcript Analysis (NETest) in GEP-NETs Treated With Somatostatin Analogs Defines Therapy

Abstract: NETest values (80-100%) were more accurate and occurred at a significantly earlier time point than CgA and predicted SSA treatment response.

Cited by 111 publications

References 39 publications

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive

Measurement of circulating transcript levels (NETest) to detect disease recurrence and improve follow‐up after curative surgical resection of well‐differentiated pancreatic neuroendocrine tumors

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