title: Early Changes in Circulating Tumor Cells Are Associated with Response and Survival Following Treatment of Metastatic Neuroendocrine Neoplasms.
abstract: OBJECTIVE
  To investigate posttreatment circulating tumor cell (CTC) counts in patients with neuroendocrine neoplasms (NENs) as a predictive biomarker for disease progression and overall survival (OS).
  
  
  METHODS
  Patients with metastatic NENs commencing therapy were prospectively recruited (n = 138). Blood samples were obtained for evaluation of CTCs using the CellSearch platform and for chromogranin A (CgA) at baseline, three to five (median, 4.3) weeks and 10 to 15 (median 13.7) weeks after commencing therapy. Radiologic response and OS data were collected.
  
  
  RESULTS
  There was a significant association between first posttreatment CTC count and progressive disease (PD; P < 0.001). Only 8% of patients with a favorable "CTC response" (0 CTCs at baseline and 0 at first posttreatment time-point; or ≥50% reduction from baseline) had PD compared with 60% in the unfavorable group (<50% reduction or increase). Changes in CTCs were strongly associated with OS (P < 0.001), the best prognostic group being patients with 0 CTCs before and after therapy; followed by those with ≥50% reduction in CTCs [hazard ratio (HR), 3.31]; with those with a <50% reduction or increase in CTCs (HR, 5.07) having the worst outcome. In multivariate analysis, changes in CTCs had the strongest association with OS (HR, 4.13; P = 0.0002). Changes in CgA were not significantly associated with survival.
  
  
  CONCLUSIONS
  Changes in CTCs are associated with response to treatment and OS in metastatic NENs, suggesting CTCs may be useful as surrogate markers to direct clinical decision making.
authors.affiliation: UCL Cancer Institute, London, United Kingdom. Neuroendocrine Tumour Unit, Department of Gastroenterology, Royal Free Hospital, London, United Kingdom. Department of Gastroenterology, University Hospital of Wales, Cardiff & Vale University Hospital Board, Cardiff, United Kingdom.
authors.forename: Mohid S
authors.initials: MS
authors.lastname: Khan
authors.affiliation: Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom.
authors.forename: Amy A
authors.initials: AA
authors.lastname: Kirkwood
authors.affiliation: UCL Cancer Institute, London, United Kingdom.
authors.forename: Theodora
authors.initials: T
authors.lastname: Tsigani
authors.affiliation: UCL Cancer Institute, London, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Lowe
authors.affiliation: UCL Cancer Institute, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Goldstein
authors.affiliation: UCL Cancer Institute, London, United Kingdom.
authors.forename: John A
authors.initials: JA
authors.lastname: Hartley
authors.affiliation: Neuroendocrine Tumour Unit, Department of Gastroenterology, Royal Free Hospital, London, United Kingdom.
authors.forename: Martyn E
authors.initials: ME
authors.lastname: Caplin
authors.affiliation: UCL Cancer Institute, London, United Kingdom. Department of Oncology, Royal Free Hospital, London, United Kingdom. t.meyer@ucl.ac.uk.
authors.forename: Tim
authors.initials: T
authors.lastname: Meyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D053379:Chromogranin A / Q000378:metabolism; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D018358:Neuroendocrine Tumors / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D053379:Chromogranin A