K Öberg1, A Califano2, J R Strosberg3, S Ma4, U Pape5, L Bodei6, G Kaltsas7, C Toumpanakis8, J R Goldenring9, A Frilling10, S Paulson11. 1. Department of Endocrine Oncology, University Hospital, Uppsala, Sweden. Electronic address: kjell.oberg@medsci.uu.se. 2. Department of Systems Biology, Columbia University, New York, USA. 3. Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, USA. 4. Department of Biostatistics, Yale University, New Haven, USA. 5. Department of Internal Medicine and Gastroenterology, Asklepios Kliniken, Hamburg, Germany. 6. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA. 7. Division of Endocrinology, Department of Pathophysiology, University of Athens, Athens, Greece. 8. Department of Gastroenterology, University College of London, London, UK. 9. Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, USA. 10. Department of Endocrine Surgery, Imperial College London, London, UK. 11. Division of Medical Oncology, Baylor Charles A Sammons Cancer Center, Dallas, USA.
Abstract
BACKGROUND: The lack of an accurate blood biomarker in neuroendocrine tumor (NET) disease has hindered management. The advance of genomic medicine and the development of molecular biomarkers has provided a strategy-liquid biopsy-to facilitate real-time management. We reviewed the role of a blood mRNA-based NET biomarker, the NETest, as an in vitro diagnostic (IVD). PATIENTS AND METHODS: A systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was undertaken. The methodological quality was evaluated using the QUADAS-2 tool. We identified ten original scientific papers that met the inclusion criteria. These were assessed by qualitative analysis and thereafter meta-analysis. Data were pooled and a median [95% confidence interval (CI)] diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) were calculated. For the meta-analysis, a generic inverse variance method was undertaken using the accuracy and area under the curve (AUC) data. RESULTS: The ten studies exhibited moderate to high methodological quality. They evaluated NETest usage both as a diagnostic and as a monitoring tool. The meta-analysis identified the diagnostic accuracy of the NETest to be 95%-96% with a mean DOR of 5 853, +LR of 195, and -LR of 0.06. The NETest was 84.5%-85.5% accurate in differentiating stable disease from progressive disease. As a marker of natural history, the accuracy was 91.5%-97.8%. As an interventional/response biomarker, the accuracy was 93.7%-97.4%. The pooled AUC for the NETest was 0.954 ± 0.005, with a z-statistic of 175.06 (P < 0.001). CONCLUSIONS: The NETest is an accurate biomarker suitable for clinical use in NET disease management. The meta-analysis supports the utility of the NETest as an IVD to establish a diagnosis and monitor therapeutic efficacy. The use of this as a biomarker provides information relevant to NET management consistent with observations regarding utility of liquid biopsies in other oncological disciplines.
BACKGROUND: The lack of an accurate blood biomarker in neuroendocrine tumor (NET) disease has hindered management. The advance of genomic medicine and the development of molecular biomarkers has provided a strategy-liquid biopsy-to facilitate real-time management. We reviewed the role of a blood mRNA-based NET biomarker, the NETest, as an in vitro diagnostic (IVD). PATIENTS AND METHODS: A systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was undertaken. The methodological quality was evaluated using the QUADAS-2 tool. We identified ten original scientific papers that met the inclusion criteria. These were assessed by qualitative analysis and thereafter meta-analysis. Data were pooled and a median [95% confidence interval (CI)] diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) were calculated. For the meta-analysis, a generic inverse variance method was undertaken using the accuracy and area under the curve (AUC) data. RESULTS: The ten studies exhibited moderate to high methodological quality. They evaluated NETest usage both as a diagnostic and as a monitoring tool. The meta-analysis identified the diagnostic accuracy of the NETest to be 95%-96% with a mean DOR of 5 853, +LR of 195, and -LR of 0.06. The NETest was 84.5%-85.5% accurate in differentiating stable disease from progressive disease. As a marker of natural history, the accuracy was 91.5%-97.8%. As an interventional/response biomarker, the accuracy was 93.7%-97.4%. The pooled AUC for the NETest was 0.954 ± 0.005, with a z-statistic of 175.06 (P < 0.001). CONCLUSIONS: The NETest is an accurate biomarker suitable for clinical use in NET disease management. The meta-analysis supports the utility of the NETest as an IVD to establish a diagnosis and monitor therapeutic efficacy. The use of this as a biomarker provides information relevant to NET management consistent with observations regarding utility of liquid biopsies in other oncological disciplines.
Authors: Irvin M Modlin; Mark Kidd; Kjell Oberg; Massimo Falconi; Pier Luigi Filosso; Andrea Frilling; Anna Malczewska; Ronald Salem; Christos Toumpanakis; Faidon-Marios Laskaratos; Stefano Partelli; Matteo Roffinella; Claudia von Arx; Beata Kos Kudla; Lisa Bodei; Ignat A Drozdov; Alexandra Kitz Journal: Ann Surg Oncol Date: 2021-05-18 Impact factor: 5.344
Authors: I M Modlin; M Kidd; M Falconi; P L Filosso; A Frilling; A Malczewska; C Toumpanakis; G Valk; K Pacak; L Bodei; K E Öberg Journal: Ann Oncol Date: 2021-08-11 Impact factor: 51.769
Authors: Catherine G Tran; Scott K Sherman; Aaron T Scott; Po Hien Ear; Chandrikha Chandrasekharan; Andrew M Bellizzi; Joseph S Dillon; Thomas M O'Dorisio; James R Howe Journal: Ann Surg Oncol Date: 2020-07-11 Impact factor: 5.344