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

Author:

Oberg Kjell1,Krenning Eric2,Sundin Anders1,Bodei Lisa3,Kidd Mark4,Tesselaar Margot5,Ambrosini Valentina6,Baum Richard P7,Kulke Matthew8,Pavel Marianne9,Cwikla Jaroslaw10,Drozdov Ignat4,Falconi Massimo11,Fazio Nicola12,Frilling Andrea13,Jensen Robert14,Koopmans Klaus15,Korse Tiny5,Kwekkeboom Dik2,Maecke Helmut16,Paganelli Giovanni17,Salazar Ramon18,Severi Stefano17,Strosberg Jonathan19,Prasad Vikas9,Scarpa Aldo20,Grossman Ashley21,Walenkamp Annemeik22,Cives Mauro19,Virgolini Irene23,Kjaer Andreas24,Modlin Irvin M25

Affiliation:

1. 1Uppsala UniversityUppsala, Sweden

2. 2Erasmus Medical CenterRotterdam, Netherlands

3. 3Memorial Sloan Kettering Cancer CenterNew York, New York, USA

4. 4Wren LaboratoriesBranford, Connecticut, USA

5. 5Netherlands Cancer InstituteAmsterdam, Netherlands

6. 6University of BolognaBologna, Italy

7. 7Zentralklinik Bad BerkaBad Berka, Germany

8. 8Dana Farber Cancer InstituteBoston, Massachusetts, USA

9. 9Charite HospitalBerlin, Germany

10. 10University of Warmia and MazuryOlsztyn, Poland

11. 11Ospedale San RaffaeleMilan, Italy

12. 12IEO (European Institute of Oncology)Milan, Italy

13. 13Imperial College LondonLondon, UK

14. 14National Institutes of HealthBethesda, Maryland, USA

15. 15Martini ZiekenhuisGroningen, Netherlands

16. 16University Hospital FreiburgFreiburg, Germany

17. 17Instituto Scientifico Romagnolo per lo Studio e la Cura dei TumoriMeldola, Italy

18. 18Instituto Catala d’OncologiaBarcelona, Spain

19. 19H. Lee Moffitt Cancer CenterTampa, Florida, USA

20. 20University of VeronaVerona, Italy

21. 21Univeristy of OxfordOxford, UK

22. 22University of GroningenGroningen, Netherlands

23. 23Medical University InnsbruckInnsbruck, Austria

24. 24Copenhagen UniversityCopenhagen, Denmark

25. 25Yale UniversityNew Haven, Connecticut, USA

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.

Publisher

Bioscientifica

Subject

Endocrinology,Endocrinology, Diabetes and Metabolism,Internal Medicine

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