Circulating and disseminated tumor cells in pancreatic cancer and their role in patient prognosis: a systematic review and meta-analysis

David Stephenson, Christopher Nahm _, Terence Chua, Anthony Gill, Anubhav Mittal, Philip de Reuver and Jaswinder Samra

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Oncotarget. 2017; 8:107223-107236. https://doi.org/10.18632/oncotarget.19928

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David Stephenson1, Christopher Nahm1,2, Terence Chua2, Anthony Gill1,3, Anubhav Mittal1,2, Philip de Reuver4 and Jaswinder Samra1,2

1Sydney Medical School, University of Sydney, Camperdown, Sydney, Australia

2Upper GI Surgical Unit, Department of Gastrointestinal Surgery, Royal North Shore Hospital, St. Leonards, Sydney, Australia

3Cancer Diagnosis and Pathology, Kolling Institute, Royal North Shore Hospital, St. Leonards, Sydney, Australia

4Department of Surgery, Radboud University Medical Centre, Nijmegen, The Netherlands

Correspondence to:

Christopher Nahm, email: [email protected]

Keywords: circulating tumor cells, disseminated tumor cells, pancreatic cancer, prognosis

Received: May 30, 2017     Accepted: July 25, 2017     Published: August 04, 2017


Background: Disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) have been postulated to seed metastases and contribute to poorer patient outcomes in many types of solid cancer. To date, no systematic reviews have examined the role of both DTCs and CTCs in pancreatic cancer. We aimed to determine the prognostic value of DTCs/CTCs in pancreatic cancer using a systematic review and meta-analysis.

Materials and Methods: A comprehensive literature search identified studies examining DTCs and CTCs in the bone marrow and blood of pancreatic cancer patients at diagnosis with follow-up to determine disease-free/progression-free survival (DFS/PFS) and overall survival (OS). Statistical analyses were performed to determine the hazard ratio (HR) of DTCs/CTCs on DFS/PFS and OS.

Results: The literature search identified 16 articles meeting the inclusion criteria. The meta-analysis demonstrated statistically significant HR differences in DFS/PFS (HR = 1.93, 95% CI 1.19–3.11, P = 0.007) and OS (HR = 1.84, 95% CI 1.37–2.45, P =< 0.0001), indicating patients with detectable DTCs/CTCs at diagnosis have worse prognoses. Subgroup analyses suggested CTCs in the peripheral blood (HR =2.03) were more indicative of poor OS prognosis than DTCs in the bone marrow (HR = 1.91), although the difference between these was not statistically significant. Positivity of the CellSearch detection method for DTC/CTC had the highest correlation with decreased OS (HR = 2.79) while immunodetection (HR = 1.91) and RT-PCR (HR = 1.25) were less effective in determining prognosis.

Conclusion: The detection of DTCs/CTCs at diagnosis is associated with poorer DFS/PFS and OS in pancreatic cancer.

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