title: Blood measurement of neuroendocrine gene transcripts defines the effectiveness of operative resection and ablation strategies.
abstract: BACKGROUND
  Surgery is the only curative treatment for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but the prediction of residual disease/recurrence is limited in the absence of optimal biomarkers. We examined whether a blood-based multianalyte neuroendocrine gene transcript assay (NETest) would define tumor cytoreduction and therapeutic efficacy.
  
  
  METHODS
  The NETest is a polymerase chain reaction-based analysis of 51 genes. Disease activity is scaled 0-100%; minimal <14%, low 14-47%, and high >47%. A total of 35 GEP-NETs in 2 groups were evaluated. I: after surgery (R0, n = 15; residual, n = 12); II: nonsurgery (n = 8: embolization with gel-foam alone [bland: n = 3]), transarterial chemoembolization (n = 2), and radiofrequency embolization (n = 3). Measurement (quantitative real-time-polymerase chain reaction) and chromogranin A (CgA; enzyme-linked immunosorbent assay) were undertaken preoperatively and 1 month after treatment.
  
  
  RESULTS
  NETest score was increased in 35 (100%) preoperatively; 14 (40%) had increased CgA (χ(2) = 30, P < 2 × 10(-8)). Resection reduced NETest from 80 ± 5% to 29% ± 5, (P < .0001). CgA decrease was insignificant (14.3 ± 1.6 U/L to 12.2 ± 1.7 U/L). NETest decreases correlated with diminished tumor volume (R(2) = 0.29, P = .03). Cytoreduction significantly reduced NETest from 82 ± 3% to 41% ± 6, P < .0001). CgA was not decreased (21.4 ± 5.5 U/L to 18.4 ± 10.1 U/L). Four (36%) of 11 R0s with increased NETest at 1 month developed positive imaging (sensitivity 100%, specificity 20%). One hundred percent (ablated group) were transcript- and image-positive.
  
  
  CONCLUSIONS
  Blood NET transcripts delineate surgical resection/cytoreduction and facilitate identification of residual disease.
authors.affiliation: Surgery, Emeritus Prof, Yale University School of Medicine, New Haven, CT. Electronic address: imodlin@optonline.net.
authors.forename: Irvin M
authors.initials: IM
authors.lastname: Modlin
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Frilling
authors.affiliation: Department of Surgery, Yale University School of Medicine, New Haven, CT.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Salem
authors.affiliation: Wren Laboratories, Branford, CT.
authors.forename: Daniele
authors.initials: D
authors.lastname: Alaimo
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Drymousis
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Harpreet S
authors.initials: HS
authors.lastname: Wasan
authors.affiliation: Wren Laboratories, Branford, CT.
authors.forename: Stephen
authors.initials: S
authors.lastname: Callahan
authors.affiliation: Department of Colorectal Surgery, St Mark's Hospital, London, UK.
authors.forename: Omar
authors.initials: O
authors.lastname: Faiz
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Lei
authors.initials: L
authors.lastname: Weng
authors.affiliation: Wren Laboratories, Branford, CT.
authors.forename: Nancy
authors.initials: N
authors.lastname: Teixeira
authors.affiliation: Wren Laboratories, Branford, CT.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bodei
authors.affiliation: Wren Laboratories, Branford, CT.
authors.forename: Ignat
authors.initials: I
authors.lastname: Drozdov
authors.affiliation: Wren Laboratories, Branford, CT.
authors.forename: Mark
authors.initials: M
authors.lastname: Kidd
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D065426:Cytoreduction Surgical Procedures; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007414:Intestinal Neoplasms / Q000097:blood* / Q000235:genetics / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000235:genetics; D018358:Neuroendocrine Tumors / Q000097:blood* / Q000235:genetics / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000235:genetics / Q000601:surgery; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000097:blood* / Q000235:genetics / Q000601:surgery; D014158:Transcription, Genetic
chemical_list: D014408:Biomarkers, Tumor