Circulating Transcript Analysis (NETest) in GEP-NETs Treated With Somatostatin Analogs Defines Therapy.
BACKGROUND
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).


METHODS
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.


METHODS
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).


METHODS
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.
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.
Jarosław B
JB
Ćwikła
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.
Lisa
L
Bodei
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.
Agnieszka
A
Kolasinska-Ćwikła
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.
Artur
A
Sankowski
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.
Irvin M
IM
Modlin
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.
Mark
M
Kidd
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D053379:Chromogranin A / Q000097:blood; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004067:Digestive System Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015282:Octreotide / Q000627:therapeutic use*; D011446:Prospective Studies; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; C506150:CHGA protein, human; D053379:Chromogranin A; D013004:Somatostatin; C517782:pasireotide; D015282:Octreotide