Journal
JOURNAL OF CLINICAL ONCOLOGY
Volume 31, Issue 3, Pages 365-372Publisher
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2012.44.2905
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Funding
- University College London (UCL) Experimental Cancer Medicine Centre [C34/A7279]
- IPSEN Fund Clinical Research Fellowship
- UCL Hospitals/UCL National Institute for Health Research Biomedical Research Centre
- Bottoms Up Charity
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Purpose To determine the prognostic significance of circulating tumor cells (CTCs) in patients with neuroendocrine cancer. Patients and Methods In this single-center prospective study, 176 patients with measurable metastatic neuroendocrine tumors (NETs) were recruited. CTCs were measured using a semiautomated technique based on immunomagnetic separation of epithelial cell adhesion molecule-expressing cells. Results Overall, 49% patients had >= one CTC, 42% had >= two CTCs, and 30% had >= five CTCs in 7.5 mL blood. Presence of CTCs was associated with increased burden, increased tumor grade, and elevated serum chromogranin A (CgA). Using a 90-patient training set and 85-patient validation set, we defined a cutoff of < one or > one as the optimal prognostic threshold with respect to progression-free survival (PFS). Applying this threshold, the presence of >= one CTC was associated with worse PFS and overall survival (OS; hazard ratios [HRs], 6.6 and 8.0, respectively; both P < .001). In multivariate analysis, CTCs remained significant when other prognostic markers, grade, tumor burden, and CgA were included. Within grades, presence of CTCs was able to define a poor prognostic subgroup. For grade 1, HRs were 5.0 for PFS (P = .017) and 7.2 for OS (P = .023); for grade 2, HRs were 3.5 for PFS (P = .018) and 5.2 for OS (P = .036). Conclusion CTCs are a promising prognostic marker for patients with NETs and should be assessed in the context of clinical trials with defined tumor subtypes and therapy. J Clin Oncol 31:365-372. (C) 2012 by American Society of Clinical Oncology
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