American Association for Cancer Research, Clinical Cancer Research, 1(22), p. 79-85, 2016
DOI: 10.1158/1078-0432.ccr-15-1008
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Abstract Purpose: 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). Experimental Design: 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. Clin Cancer Res; 22(1); 79–85. ©2015 AACR.