A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management

Kjell Oberg; Eric Krenning; Anders Sundin; Lisa Bodei; Mark Kidd; Margot Tesselaar; Valentina Ambrosini; Richard P Baum; Matthew Kulke; Marianne Pavel; Jaroslaw Cwikla; Ignat Drozdov; Massimo Falconi; Nicola Fazio; Andrea Frilling; Robert Jensen; Klaus Koopmans; Tiny Korse; Dik J Kwekkeboom; Helmut Maecke; Giovanni Paganelli; Ramon Salazar; Stefano Severi; Jonathan Strosberg; Vikas Prasad; Aldo Scarpa; Ashley Grossman; Annemeik Walenkamp; Mauro Cives; Irene Virgolini; Andreas Kjaer; Irvin M Modlin

doi:10.1530/EC-16-0043

A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management

Kjell Oberg, Eric Krenning, Anders Sundin, Lisa Bodei, Mark Kidd, Margot Tesselaar, Valentina Ambrosini, Richard P Baum, Matthew Kulke, Marianne Pavel, Jaroslaw Cwikla, Ignat Drozdov, Massimo Falconi, Nicola Fazio, Andrea Frilling, Robert Jensen, Klaus Koopmans, Tiny Korse, Dik J Kwekkeboom, Helmut MaeckeGiovanni Paganelli, Ramon Salazar, Stefano Severi, Jonathan Strosberg, Vikas Prasad, Aldo Scarpa, Ashley Grossman, Annemeik Walenkamp, Mauro Cives, Irene Virgolini, Andreas Kjaer, Irvin M Modlin

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Abstract

The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (>75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

Original language	English
Journal	Endocrine Connections
Volume	5
Issue number	5
Pages (from-to)	174-187
Number of pages	14
ISSN	2049-3614
DOIs	https://doi.org/10.1530/EC-16-0043
Publication status	Published - 1 Sept 2016

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Journal Article

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A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease managementFinal published version, 2.32 MBLicence: CC BY-NC

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Oberg, K., Krenning, E., Sundin, A., Bodei, L., Kidd, M., Tesselaar, M., Ambrosini, V., Baum, R. P., Kulke, M., Pavel, M., Cwikla, J., Drozdov, I., Falconi, M., Fazio, N., Frilling, A., Jensen, R., Koopmans, K., Korse, T., Kwekkeboom, D. J., ... Modlin, I. M. (2016). A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management. Endocrine Connections, 5(5), 174-187. https://doi.org/10.1530/EC-16-0043

Oberg, K, Krenning, E, Sundin, A, Bodei, L, Kidd, M, Tesselaar, M, Ambrosini, V, Baum, RP, Kulke, M, Pavel, M, Cwikla, J, Drozdov, I, Falconi, M, Fazio, N, Frilling, A, Jensen, R, Koopmans, K, Korse, T, Kwekkeboom, DJ, Maecke, H, Paganelli, G, Salazar, R, Severi, S, Strosberg, J, Prasad, V, Scarpa, A, Grossman, A, Walenkamp, A, Cives, M, Virgolini, I, Kjaer, A & Modlin, IM 2016, 'A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management', Endocrine Connections, vol. 5, no. 5, pp. 174-187. https://doi.org/10.1530/EC-16-0043

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abstract = "The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (>75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.",

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T2 - imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management

AU - Oberg, Kjell

AU - Krenning, Eric

AU - Sundin, Anders

AU - Bodei, Lisa

AU - Kidd, Mark

AU - Tesselaar, Margot

AU - Ambrosini, Valentina

AU - Baum, Richard P

AU - Kulke, Matthew

AU - Pavel, Marianne

AU - Cwikla, Jaroslaw

AU - Drozdov, Ignat

AU - Falconi, Massimo

AU - Fazio, Nicola

AU - Frilling, Andrea

AU - Jensen, Robert

AU - Koopmans, Klaus

AU - Korse, Tiny

AU - Kwekkeboom, Dik J

AU - Maecke, Helmut

AU - Paganelli, Giovanni

AU - Salazar, Ramon

AU - Severi, Stefano

AU - Strosberg, Jonathan

AU - Prasad, Vikas

AU - Scarpa, Aldo

AU - Grossman, Ashley

AU - Walenkamp, Annemeik

AU - Cives, Mauro

AU - Virgolini, Irene

AU - Kjaer, Andreas

AU - Modlin, Irvin M

PY - 2016/9/1

Y1 - 2016/9/1

N2 - The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (>75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

AB - The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (>75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

KW - Journal Article

U2 - 10.1530/EC-16-0043

DO - 10.1530/EC-16-0043

M3 - Journal article

C2 - 27582247

SN - 2049-3614

VL - 5

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EP - 187

JO - Endocrine Connections

JF - Endocrine Connections

IS - 5

ER -

A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management

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