Early Changes in Circulating Tumor Cells Are Associated with Response and Survival Following Treatment of Metastatic Neuroendocrine Neoplasms

Clinical Cancer Research - Tập 22 Số 1 - Trang 79-85 - 2016
Mohid S. Khan1,2,3, Amy A. Kirkwood4, Theodora Tsigani1, Helen L. Lowe1, Robert M. Goldstein1, John A. Hartley1, Martyn Caplin2, Tim Meyer1,5
11UCL Cancer Institute, London, United Kingdom.
22Neuroendocrine Tumour Unit, Department of Gastroenterology, Royal Free Hospital, London, United Kingdom.
33Department of Gastroenterology, University Hospital of Wales, Cardiff & Vale University Hospital Board, Cardiff, United Kingdom.
44Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom.
55Department of Oncology, Royal Free Hospital, London, United Kingdom.

Tóm tắt

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.

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Clinical Cancer Research

Tập 22 Số 1

79-85

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