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

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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 < 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 < 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 < 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.

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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.

Disclosures

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. 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, and James S. Tomlinson have no disclosures to declare.

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Authors and Affiliations

  1. Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA

    Colin M. Court MD, Jacob S. Ankeny MD, Shonan Sho MD, Paul Winograd MD, Shuang Hou PhD, Mark D. Girgis MD, Vatche G. Agopian MD & James S. Tomlinson MD, PhD

  2. Department of Surgery, Veteran’s Health Administration, Los Angeles, CA, USA

    Colin M. Court MD, Jacob S. Ankeny MD, Shonan Sho MD, Paul Winograd MD & James S. Tomlinson MD, PhD

  3. Department of Molecular, Cellular, and Integrative Physiology, University of California Los Angeles, Los Angeles, CA, USA

    Colin M. Court MD & Thomas G. Graeber PhD

  4. Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA

    Shuang Hou PhD, Min Song MD, Thomas G. Graeber PhD & Hsian-Rong Tseng PhD

  5. Department of Hematology/Oncology, University of California Los Angeles, Los Angeles, CA, USA

    Zev A. Wainberg MD

  6. California NanoSystems Institute (CNSI), University of California Los Angeles, Los Angeles, CA, USA

    James S. Tomlinson MD, PhD

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  1. Colin M. Court MD
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Correspondence to James S. Tomlinson MD, PhD.

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Court, C.M., Ankeny, J.S., Sho, S. et al. Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer. Ann Surg Oncol 25, 1000–1008 (2018). https://doi.org/10.1245/s10434-017-6290-8

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  • DOI: https://doi.org/10.1245/s10434-017-6290-8

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