Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer

Colin M. Court, Jacob S. Ankeny, Shonan Sho, Paul Winograd, Shuang Hou, Min Song, Zev A. Wainberg, Mark D. Girgis, Thomas G. Graeber, Vatche G. Agopian, Hsian Rong Tseng, James S. Tomlinson

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Background: Occult metastatic tumors, below imaging thresholds, are a limitation of staging systems that rely on cross-sectional imaging alone and are a cause of the routine understaging of pancreatic ductal adenocarcinomas (PDACs). We investigated circulating tumor cells (CTCs) as a preoperative predictor of occult metastatic disease and as a prognostic biomarker for PDAC patients. Experimental Design: A total of 126 patients (100 with cancer, 26 with benign disease) were enrolled in our study and CTCs were identified and enumerated from 4 mL of venous blood using the microfluidic NanoVelcro assay. CTC enumeration was correlated with clinicopathologic variables and outcomes following both surgical and systemic therapies. Results: CTCs were identified in 78% of PDAC patients and CTC counts correlated with increasing stage (ρ = 0.42, p OpenSPiltSPi 0.001). Of the 53 patients taken for potentially curative surgery, 13 (24.5%) had occult metastatic disease intraoperatively. Patients with occult disease had significantly more CTCs than patients with local disease only (median 7 vs. 1 CTC, p OpenSPiltSPi 0.0001). At a cut-off of three or more CTCs/4 mL, CTCs correctly identified patients with occult metastatic disease preoperatively (area under the receiver operating characteristic curve 0.82, 95% confidence interval (CI) 0.76–0.98, p OpenSPiltSPi 0.0001). CTCs were a univariate predictor of recurrence-free survival following surgery [hazard ratio (HR) 2.36, 95% CI 1.17–4.78, p = 0.017], as well as an independent predictor of overall survival on multivariate analysis (HR 1.38, 95% CI 1.01–1.88, p = 0.040). Conclusions: CTCs show promise as a prognostic biomarker for PDAC patients at all stages of disease being treated both medically and surgically. Furthermore, CTCs demonstrate potential as a preoperative biomarker for identifying patients at high risk of occult metastatic disease.

Original languageEnglish (US)
Pages (from-to)1000-1008
Number of pages9
JournalAnnals of Surgical Oncology
Volume25
Issue number4
DOIs
StatePublished - Apr 1 2018
Externally publishedYes

Bibliographical note

Funding Information:
ACKNOWLEDGEMENT This work was funded in part by a University of California Los Angeles (UCLA) Jonsson Comprehensive Cancer Center Impact Grant, as well as an award provided by NantOmics. The authors would like to thank Dr. William Isacoff, Dr. Howard Reber, Dr. Joe Hines, and Dr. Timothy Donahue for assistance in obtaining patient samples. The NanoVelcro chips used in this research were supported by research Grant (R33 CA174562 and U01 CA198900) and a Small Business Innovation Research (SBIR) grant (R44 CA180482) from the National Institutes of Health.

Funding Information:
This work was funded in part by a University of California Los Angeles (UCLA) Jonsson Comprehensive Cancer Center Impact Grant, as well as an award provided by NantOmics. The authors would like to thank Dr. William Isacoff, Dr. Howard Reber, Dr. Joe Hines, and Dr. Timothy Donahue for assistance in obtaining patient samples. The NanoVelcro chips used in this research were supported by research Grant (R33 CA174562 and U01 CA198900) and a Small Business Innovation Research (SBIR) grant (R44 CA180482) from the National Institutes of Health. The intellectual property that is associated with this study has been licensed to CytoLumina Technologies Corp. Hsian-Rong Tseng has financial interests in this company, given his roles as one of the company?s co-founders.

Publisher Copyright:
© 2018, Society of Surgical Oncology.

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