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Measurement of circulating tumor cells in squamous cell carcinoma of the head and neck and patient outcomes

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Abstract

Objectives

We report the outcomes of patients with squamous cell carcinoma of the head and neck (HNSCC) whose circulating tumor cells (CTCs) were quantified using surface-enhanced Raman scattering (SERS) nanotechnology.

Methods

SERS tagged with EGF was used to directly measure targeted CTCs. Patient charts were retrospectively reviewed. An optimal cut point for CTCs in 7.5 ml of peripheral blood predictive of for distant metastasis-free survival (DMFS) was identified by maximizing the log-rank statistic. An ROC analysis was also performed.

Results

Of 82 patients, 13 experienced metastatic progression. The optimal cut point for DMFS was 675 CTCs (p = 0.047). For those with distant recurrence (n = 13) versus those without distant recurrence (n = 69), the CTC cut point which results in the largest combined sensitivity and specificity values is also 675 (sensitivity = 69%, specificity = 68%).

Conclusion

Liquid biopsy techniques in HNSCC show promise as a means of identifying patients at greater risk of disease progression.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.

    Article  PubMed  Google Scholar 

  2. Zarbo RJ, Crissman JD. The surgical pathology of head and neck cancer. Semin Oncol. 1988;15(1):10–9.

    CAS  PubMed  Google Scholar 

  3. Jatana KR, Balasubramanian P, Lang JC, et al. Significance of circulating tumor cells in patients with squamous cell carcinoma of the head and neck: initial results. Arch Otolaryngol Head Neck Surg. 2010;136(12):1274–9.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Magnano M, De Stefani A, Lerda W, et al. Prognostic factors of cervical lymph node metastasis in head and neck squamous cell carcinoma. Tumori. 1997;83(6):922–6.

    Article  CAS  PubMed  Google Scholar 

  5. Leemans CR, Tiwari R, Nauta JJ, van der Waal I, Snow GB. Regional lymph node involvement and its significance in the development of distant metastases in head and neck carcinoma. Cancer. 1993;71(2):452–6.

    Article  CAS  PubMed  Google Scholar 

  6. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ashworth T. A case of cancer in which cells similar to those in the tumors were seen in the blood after death. Med J Aust. 1869;14:146–9.

    Google Scholar 

  8. Pantel K, Speicher MR. The biology of circulating tumor cells. Oncogene. 2016;35(10):1216–24.

    Article  CAS  PubMed  Google Scholar 

  9. Cristofanilli M. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. Semin Oncol. 2006;33(3 Suppl 9):S9–14.

    Article  PubMed  Google Scholar 

  10. Cohen SJ, Punt CJ, Iannotti N, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(19):3213–21.

    Article  PubMed  Google Scholar 

  11. Giuliano M, Giordano A, Jackson S, et al. Circulating tumor cells as early predictors of metastatic spread in breast cancer patients with limited metastatic dissemination. Breast Cancer Res. 2014;16(5):440.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Esmaeilsabzali H, Beischlag TV, Cox ME, Parameswaran AM, Park EJ. Detection and isolation of circulating tumor cells: principles and methods. Biotechnol Adv. 2013;31(7):1063–84.

    Article  CAS  PubMed  Google Scholar 

  13. Bednarz-Knoll N, Alix-Panabieres C, Pantel K. Clinical relevance and biology of circulating tumor cells. Breast Cancer Res. 2011;13(6):228.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Alix-Panabieres C, Pantel K. Technologies for detection of circulating tumor cells: facts and vision. Lab Chip. 2014;14(1):57–62.

    Article  CAS  PubMed  Google Scholar 

  15. Budd GT. Let me do more than count the ways: what circulating tumor cells can tell us about the biology of cancer. Mol Pharm. 2009;6(5):1307–10.

    Article  CAS  PubMed  Google Scholar 

  16. Wang X, Qian X, Beitler JJ, et al. Detection of circulating tumor cells in human peripheral blood using surface-enhanced Raman scattering nanoparticles. Can Res. 2011;71(5):1526–32.

    Article  CAS  Google Scholar 

  17. Joosse SA, Gorges TM, Pantel K. Biology, detection, and clinical implications of circulating tumor cells. EMBO Mol Med. 2015;7(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  18. Kneipp K, Kneipp H, Itzkan I, Dasari RR, Feld MS. Ultrasensitive chemical analysis by Raman spectroscopy. Chem Rev. 1999;99(10):2957–76.

    Article  CAS  PubMed  Google Scholar 

  19. Contal C, O’Quigley J. An application of changepoint methods in studying the effect of age on survival in breast cancer. Comput Stat Data Anal. 1999;30(3):253–70.

    Article  Google Scholar 

  20. Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer. 2008;8(5):329–40.

    Article  CAS  PubMed  Google Scholar 

  21. Cohen SJ, Punt CJ, Iannotti N, et al. Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer. Ann Oncol. 2009;20(7):1223–9.

    Article  CAS  PubMed  Google Scholar 

  22. Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351(8):781–91.

    Article  CAS  PubMed  Google Scholar 

  23. Moreno JG, Croce CM, Fischer R, et al. Detection of hematogenous micrometastasis in patients with prostate cancer. Can Res. 1992;52(21):6110–2.

    CAS  Google Scholar 

  24. Heitzer E, Auer M, Ulz P, Geigl JB, Speicher MR. Circulating tumor cells and DNA as liquid biopsies. Genome Med. 2013;5(8):73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Maheswaran S, Sequist LV, Nagrath S, et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med. 2008;359(4):366–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Haber DA, Velculescu VE. Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA. Cancer Discov. 2014;4(6):650–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Perakis S, Speicher MR. Emerging concepts in liquid biopsies. BMC Med. 2017;15(1):75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dawson SJ, Tsui DW, Murtaza M, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368(13):1199–209.

    Article  CAS  PubMed  Google Scholar 

  29. Sausen M, Leary RJ, Jones S, et al. Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma. Nat Genet. 2013;45(1):12–7.

    Article  CAS  PubMed  Google Scholar 

  30. Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra224.

    Article  CAS  Google Scholar 

  31. Beddowes E, Sammut SJ, Gao M, Caldas C. Predicting treatment resistance and relapse through circulating DNA. Breast. 2017;34:S31–5.

    Article  PubMed  Google Scholar 

  32. Grandis JR, Tweardy DJ. Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Can Res. 1993;53(15):3579–84.

    CAS  Google Scholar 

Download references

Funding

Research reported in this publication was supported in part by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Author notes

  1. T. M. Morgan, X. Wang, and X. Qian contributed equally.

Authors and Affiliations

  1. Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, 1365 Clifton Road NE, Atlanta, GA, 30322, USA

    T. M. Morgan, R. J. Cassidy & J. J. Beitler

  2. Winship Cancer Institute, Emory University, Atlanta, GA, USA

    T. M. Morgan, X. Wang, X. Qian, J. M. Switchenko, S. Nie, R. J. Cassidy, D. M. Shin & J. J. Beitler

  3. Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA

    X. Wang & D. M. Shin

  4. Department of Biomedical Engineering and Chemistry, Emory University, Atlanta, GA, USA

    X. Qian & S. Nie

  5. Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA

    J. M. Switchenko

  6. Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA

    K. R. Patel

Authors
  1. T. M. Morgan
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  2. X. Wang
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Corresponding author

Correspondence to T. M. Morgan.

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Conflicts of interest

The authors declare they have no conflicts of interest.

Research involving human participants and/or animals

This study was approved by our institutional review board and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

This research was presented in abstract form at the annual meeting of the American Radium Society; May 6–9, 2017; Colorado Springs, Colorado.

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Morgan, T.M., Wang, X., Qian, X. et al. Measurement of circulating tumor cells in squamous cell carcinoma of the head and neck and patient outcomes. Clin Transl Oncol 21, 342–347 (2019). https://doi.org/10.1007/s12094-018-1930-4

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  • DOI: https://doi.org/10.1007/s12094-018-1930-4

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