Circulating transcript analysis (NETest) in GEP-NETs treated with somatostatin analogs defines therapy

Jarosław B. Ćwikła, Lisa Bodei, Agnieszka Kolasinska-Ćwikła, Artur Sankowski, Irvin M. Modlin, Mark Kidd

Research output: Contribution to journalArticle

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Abstract

Context: Early and precise delineation of therapeutic responses are key issues in neuroendocrine neoplasm/tumor management. Imaging is currently used but exhibits limitations in sensitivity and specificity. The utility of biomarkers is unclear. Objective, Setting, and Design: This prospective cohort study (11mo)sought to determine whether measurements of circulating neuroendocrine tumor transcripts (NETest) predict responses to somatostatin analogs (SSAs). Patients: The test set consisted of 35 SSA-treated gastroenteropancreatic-NETs (RECISTevaluated). The prospective set consisted of 28 SSA-treated Grade 1-Grade 2 GEP-NETs. Intervention(s): Whole blood for transcript analysis (NETest) and plasma for ChromograninA(CgA) (baseline), were collected every 4 weeks (prior to SSA injection). Morphologic (multidetector computed tomography/MRI) and functional imaging (99mTc-[HYNIC, Tyr3]-Octreotide) was undertaken at entry and 6-month intervals until progression (RECIST 1.0). Main Outcome Measure(s): Treatment response. Results: Test set: NETest (≥80%; scale, 0-100%) differentiated stable (SD) and progressive (PD) disease (P25% increase; eight developed PD; four, SD. NETest (P=.002) and grade (P=.054) were the only factors associated with treatment response. Multiple regression analysis established that the NETest could predict disease progression (P=.0002). NETest changes occurred significantly earlier (146 d prior to progression vs 56 d CgA; P <.0001; χ2 = 19) and in more patients (100 vs 57%; P <.02). Conclusions: NETest values (80-100%) were more accurate and occurred at a significantly earlier time point than CgA and predicted SSA treatment response.

Original languageEnglish
Pages (from-to)E1437-E1445
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

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Somatostatin
Neuroendocrine Tumors
Tumors
Multidetector computed tomography
Somatostatin-28
Imaging techniques
Octreotide
Multidetector Computed Tomography
Biomarkers
Therapeutics
Regression analysis
Magnetic resonance imaging
Disease Progression
Blood
Cohort Studies
Regression Analysis
Magnetic Resonance Imaging
Outcome Assessment (Health Care)
Prospective Studies
Plasmas

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Ćwikła, J. B., Bodei, L., Kolasinska-Ćwikła, A., Sankowski, A., Modlin, I. M., & Kidd, M. (2015). Circulating transcript analysis (NETest) in GEP-NETs treated with somatostatin analogs defines therapy. Journal of Clinical Endocrinology and Metabolism, 100(11), E1437-E1445. https://doi.org/10.1210/jc.2015-2792

Circulating transcript analysis (NETest) in GEP-NETs treated with somatostatin analogs defines therapy. / Ćwikła, Jarosław B.; Bodei, Lisa; Kolasinska-Ćwikła, Agnieszka; Sankowski, Artur; Modlin, Irvin M.; Kidd, Mark.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 11, 01.11.2015, p. E1437-E1445.

Research output: Contribution to journalArticle

Ćwikła, JB, Bodei, L, Kolasinska-Ćwikła, A, Sankowski, A, Modlin, IM & Kidd, M 2015, 'Circulating transcript analysis (NETest) in GEP-NETs treated with somatostatin analogs defines therapy', Journal of Clinical Endocrinology and Metabolism, vol. 100, no. 11, pp. E1437-E1445. https://doi.org/10.1210/jc.2015-2792
Ćwikła, Jarosław B. ; Bodei, Lisa ; Kolasinska-Ćwikła, Agnieszka ; Sankowski, Artur ; Modlin, Irvin M. ; Kidd, Mark. / Circulating transcript analysis (NETest) in GEP-NETs treated with somatostatin analogs defines therapy. In: Journal of Clinical Endocrinology and Metabolism. 2015 ; Vol. 100, No. 11. pp. E1437-E1445.
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abstract = "Context: Early and precise delineation of therapeutic responses are key issues in neuroendocrine neoplasm/tumor management. Imaging is currently used but exhibits limitations in sensitivity and specificity. The utility of biomarkers is unclear. Objective, Setting, and Design: This prospective cohort study (11mo)sought to determine whether measurements of circulating neuroendocrine tumor transcripts (NETest) predict responses to somatostatin analogs (SSAs). Patients: The test set consisted of 35 SSA-treated gastroenteropancreatic-NETs (RECISTevaluated). The prospective set consisted of 28 SSA-treated Grade 1-Grade 2 GEP-NETs. Intervention(s): Whole blood for transcript analysis (NETest) and plasma for ChromograninA(CgA) (baseline), were collected every 4 weeks (prior to SSA injection). Morphologic (multidetector computed tomography/MRI) and functional imaging (99mTc-[HYNIC, Tyr3]-Octreotide) was undertaken at entry and 6-month intervals until progression (RECIST 1.0). Main Outcome Measure(s): Treatment response. Results: Test set: NETest (≥80{\%}; scale, 0-100{\%}) differentiated stable (SD) and progressive (PD) disease (P25{\%} increase; eight developed PD; four, SD. NETest (P=.002) and grade (P=.054) were the only factors associated with treatment response. Multiple regression analysis established that the NETest could predict disease progression (P=.0002). NETest changes occurred significantly earlier (146 d prior to progression vs 56 d CgA; P <.0001; χ2 = 19) and in more patients (100 vs 57{\%}; P <.02). Conclusions: NETest values (80-100{\%}) were more accurate and occurred at a significantly earlier time point than CgA and predicted SSA treatment response.",
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