I M Modlin1, M Kidd2, L Bodei3, I Drozdov2, H Aslanian4. 1. 1] Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA [2] Wren Laboratories, Branford, Connecticut, USA. 2. Wren Laboratories, Branford, Connecticut, USA. 3. Division of Nuclear Medicine, European Institute of Oncology (IEO), Milan, Italy. 4. Section of Digestive Diseases, Yale University, New Haven, Connecticut, USA.
Abstract
OBJECTIVES: Current monoanalyte blood-based biomarkers for the diagnosis and follow-up of neuroendocrine tumors (NETs) do not achieve satisfactory metrics of sensitivity and specificity. We report the sensitivity and selectivity of the PCR-based test, the NETest, to detect tumors with reference to other benign and malignant gastrointestinal diseases. METHODS: A total of 179 cases (gastrointestinal tumors: n=81; pancreatic disease: n=98) were prospectively collected and assessed using the NETest or chromogranin A (CgA) to determine metrics for detecting small intestinal and pancreatic NETs. RESULTS: For intestinal carcinoids, the accuracy of the NETest was 93% (all NETs positive and 3 (12%) colorectal tumors were positive). CgA was positive in 80%, but 29% (n=7) of colorectal cancers were CgA positive. For pancreatic disease, the NETest accuracy was 94% (96% NETs positive, 2 (6%) of intraductal papillary mucinous neoplasms (IPMNs) were positive). The accuracy of CgA was 56% (29% of pancreatic NETs were CgA positive). Overall, the NETest was significantly more sensitive than CgA for the detection of small intestinal (area under the curve 0.98 vs. 0.75 P<0.0001) and pancreatic NETs (0.94 vs. 0.52, P<0.0001). NETest scores were elevated (P<0.05) in extensive disease and were more accurate (76-80%) than CgA levels (20-32%). The metrics of the multianalyte NETest met the performance criteria proposed by the National Institutes of Health for biomarkers, whereas CgA measurement did not. CONCLUSIONS: This study demonstrates that a blood-based multianalyte NET gene transcript measurement of well-differentiated small intestinal and pancreatic neuroendocrine tumor disease is sensitive and specific and outperforms the current monoanalyte diagnostic strategy of plasma CgA measurement.
OBJECTIVES: Current monoanalyte blood-based biomarkers for the diagnosis and follow-up of neuroendocrine tumors (NETs) do not achieve satisfactory metrics of sensitivity and specificity. We report the sensitivity and selectivity of the PCR-based test, the NETest, to detect tumors with reference to other benign and malignant gastrointestinal diseases. METHODS: A total of 179 cases (gastrointestinal tumors: n=81; pancreatic disease: n=98) were prospectively collected and assessed using the NETest or chromogranin A (CgA) to determine metrics for detecting small intestinal and pancreatic NETs. RESULTS: For intestinal carcinoids, the accuracy of the NETest was 93% (all NETs positive and 3 (12%) colorectal tumors were positive). CgA was positive in 80%, but 29% (n=7) of colorectal cancers were CgA positive. For pancreatic disease, the NETest accuracy was 94% (96% NETs positive, 2 (6%) of intraductal papillary mucinous neoplasms (IPMNs) were positive). The accuracy of CgA was 56% (29% of pancreatic NETs were CgA positive). Overall, the NETest was significantly more sensitive than CgA for the detection of small intestinal (area under the curve 0.98 vs. 0.75 P<0.0001) and pancreatic NETs (0.94 vs. 0.52, P<0.0001). NETest scores were elevated (P<0.05) in extensive disease and were more accurate (76-80%) than CgA levels (20-32%). The metrics of the multianalyte NETest met the performance criteria proposed by the National Institutes of Health for biomarkers, whereas CgA measurement did not. CONCLUSIONS: This study demonstrates that a blood-based multianalyte NET gene transcript measurement of well-differentiated small intestinal and pancreatic neuroendocrine tumor disease is sensitive and specific and outperforms the current monoanalyte diagnostic strategy of plasma CgA measurement.
Authors: P Scott Eastman; William C Manning; Ferhan Qureshi; Douglas Haney; Guy Cavet; Claire Alexander; Lyndal K Hesterberg Journal: J Pharm Biomed Anal Date: 2012-06-12 Impact factor: 3.935
Authors: G B Turner; B T Johnston; D R McCance; A McGinty; R G P Watson; C C Patterson; J E S Ardill Journal: Gut Date: 2006-03-23 Impact factor: 23.059
Authors: Eric Liu; Scott Paulson; Anthony Gulati; Jon Freudman; William Grosh; Sheldon Kafer; Prasanna C Wickremesinghe; Ronald R Salem; Lisa Bodei Journal: Oncologist Date: 2018-08-29
Authors: Kendall J Keck; Patrick Breheny; Terry A Braun; Benjamin Darbro; Guiying Li; Joseph S Dillon; Andrew M Bellizzi; Thomas M O'Dorisio; James R Howe Journal: Surgery Date: 2017-11-16 Impact factor: 3.982
Authors: Magnus Kjellman; Ulrich Knigge; Staffan Welin; Espen Thiis-Evensen; Henning Gronbaek; Camilla Schalin-Jäntti; Halfdan Sorbye; Maiken Thyregod Joergensen; Viktor Johanson; Saara Metso; Helge Waldum; Jon Arne Søreide; Tapani Ebeling; Fredrik Lindberg; Kalle Landerholm; Goran Wallin; Farhad Salem; Maria Del Pilar Schneider; Roger Belusa Journal: Neuroendocrinology Date: 2020-07-28 Impact factor: 4.914
Authors: Ashley Kieran Clift; Mark Kidd; Lisa Bodei; Christos Toumpanakis; Richard P Baum; Kjell Oberg; Irvin M Modlin; Andrea Frilling Journal: Neuroendocrinology Date: 2019-09-27 Impact factor: 5.135