Jarosław B Ćwikła1, Lisa Bodei1, Agnieszka Kolasinska-Ćwikła1, Artur Sankowski1, Irvin M Modlin1, Mark Kidd1. 1. Department of Radiology, Faculty of Medical Sciences (J.Ć.), University of Warmia and Mazury, Olsztyn 10-558, Poland; Division of Nuclear Medicine (L.B.), European Institute of Oncology, Milan 20141, Italy; Department of Oncology (A.K.-Ć.), Maria Skłodowska-Curie Memorial Cancer Center, Institute of Oncology, Warsaw 44-101, Poland; Department of Radiology (A.S.), Hospital Ministry of Internal Affairs, Warsaw 02-507, Poland; Keewaydin Consulting, Inc. (I.M.M.), Woodbridge, Connecticut 06525; and Wren Laboratories (M.K.), Branford, Connecticut 06405.
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 (11 mo) 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 Chromogranin A (CgA) (baseline), were collected every 4 weeks (prior to SSA injection). Morphologic (multidetector computed tomography/MRI) and functional imaging ((99m)Tc-[HYNIC, Tyr(3)]-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 (P < .0001). Prospective set: 28 patients (26/28 SD) undergoing standard SSA. Grading: 12 G1, 16 G2. SSA Response: progression-free survival: 315 days: 14 (50%) SD, 14 (50%) PD. NETest: Twenty had elevated (≥80%) values; 14 developed PD; six, SD. CgA: Twelve of 28 exhibited elevated baseline values and/or subsequent >25% 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; χ(2) = 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.
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 (11 mo) 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 Chromogranin A (CgA) (baseline), were collected every 4 weeks (prior to SSA injection). Morphologic (multidetector computed tomography/MRI) and functional imaging ((99m)Tc-[HYNIC,Tyr(3)]-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 (P < .0001). Prospective set: 28 patients (26/28 SD) undergoing standard SSA. Grading: 12 G1, 16 G2. SSA Response: progression-free survival: 315 days: 14 (50%) SD, 14 (50%) PD. NETest: Twenty had elevated (≥80%) values; 14 developed PD; six, SD. CgA: Twelve of 28 exhibited elevated baseline values and/or subsequent >25% 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; χ(2) = 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.
Authors: Georgios Kyriakopoulos; Vasiliki Mavroeidi; Eleftherios Chatzellis; Gregory A Kaltsas; Krystallenia I Alexandraki Journal: Ann Transl Med Date: 2018-06
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: L Bodei; M Kidd; I M Modlin; S Severi; I Drozdov; S Nicolini; D J Kwekkeboom; E P Krenning; R P Baum; G Paganelli Journal: Eur J Nucl Med Mol Imaging Date: 2015-11-23 Impact factor: 9.236