Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
2014-February Volume 31 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
2014-February Volume 31 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Levels of cell-free DNA and plasma KRAS during treatment of advanced NSCLC

  • Authors:
    • Anneli Dowler Nygaard
    • Karen-Lise Garm Spindler
    • Niels Pallisgaard
    • Rikke Fredslund Andersen
    • Anders Jakobsen
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Vejle Hospital, DK-7100 Vejle, Denmark, Department of Clinical Biochemistry, Vejle Hospital, DK-7100 Vejle, Denmark
  • Pages: 969-974
    |
    Published online on: December 6, 2013
       https://doi.org/10.3892/or.2013.2906
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumours in the western world and is associated with a poor prognosis. Biomarkers predicting prognosis and therapeutic effects are highly required, and cell-free DNA (cfDNA) may be a feasible option. Genetic mutations can be analysed in plasma and may increase the scientific use of such measurements. In the present study, we investigated: i) the dynamics of cfDNA and plasma mutated KRAS (pmKRAS) during the treatment of patients with advanced NSCLC; and ii) the prognostic value of baseline cfDNA and pmKRAS. Sixty‑nine patients were included in a prospective biomarker trial. Inclusion criteria included advanced NSCLC, candidate for first-line treatment, no previous cancer within the five years prior to this study. Blood samples were drawn at baseline, day 8 and at progression. Analyses of cfDNA and KRAS mutations in plasma were performed using an in-house qPCR assay. Evaluation of the treatment effect and status at follow-up was performed according to RECIST 1.1. The median levels of cfDNA were significantly higher at progression (9,250 alleles/ml) than at baseline (5,450 alleles/ml). Overall survival and progression-free survival were both significantly shorter in patients with high levels of cfDNA (above the 75th percentile) compared to lower levels. Only few patients harboured KRAS mutations in plasma. Two patients had no KRAS mutations in plasma at baseline, but mutations appeared in the subsequent blood samples. High baseline levels of cfDNA indicate a poor prognosis. The level changes during the treatment course with a significant increase at progression, suggesting a possible predictive value of cfDNA. The plasma KRAS status may change during treatment with potential implications for treatment selection.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Engholm G, Ferlay J, Christensen N, et al: NORDCAN: Cancer Incidence, Mortality, Prevalence and Survival in the Nordic Countries, Version 5.3 (25.04.2013). Association of the Nordic Cancer Registries. Danish Cancer Society. http://www.ancr.nu. Accessed March 2013

2 

Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: GLOBOCAN 2008 v2.0. Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. International Agency for Research on Cancer; Lyon: 2010, http://globocan.iarc.fr. Accessed March 2013

3 

Hirsch FR, Janne PA, Eberhardt WE, et al: Epidermal growth factor receptor inhibition in lung cancer: status 2012. J Thorac Oncol. 8:373–384. 2013.PubMed/NCBI

4 

D’arcangelo M, Wynes MW and Hirsch FR: The role of anaplastic lymphoma kinase inhibitors in the treatment of advanced nonsmall cell lung cancer. Curr Opin Oncol. 25:121–129. 2013.PubMed/NCBI

5 

Sasaki T, Rodig SJ, Chirieac LR and Janne PA: The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer. 46:1773–1780. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Soda M, Choi YL, Enomoto M, et al: Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 448:561–566. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Mok TS: Personalized medicine in lung cancer: what we need to know. Nat Rev Clin Oncol. 8:661–668. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Kuang Y, Rogers A, Yeap BY, et al: Noninvasive detection of EGFR T790M in gefitinib or erlotinib resistant non-small cell lung cancer. Clin Cancer Res. 15:2630–2636. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Stroun M, Maurice P, Vasioukhin V, et al: The origin and mechanism of circulating DNA. Ann NY Acad Sci. 906:161–168. 2000. View Article : Google Scholar : PubMed/NCBI

10 

Catarino R, Coelho A, Araujo A, et al: Circulating DNA: diagnostic tool and predictive marker for overall survival of NSCLC patients. PLoS One. 7:e385592012. View Article : Google Scholar : PubMed/NCBI

11 

Gautschi O, Bigosch C, Huegli B, et al: Circulating deoxyribonucleic acid as prognostic marker in non-small-cell lung cancer patients undergoing chemotherapy. J Clin Oncol. 22:4157–4164. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Nygaard AD, Garm Spindler KL, Pallisgaard N, Andersen RF and Jakobsen A: Quantification of cell free DNA as a prognostic factor in advanced NSCLC. J Can Ther. 4:1–7. 2013.

13 

Sirera R, Bremnes RM, Cabrera A, et al: Circulating DNA is a useful prognostic factor in patients with advanced non-small cell lung cancer. J Thorac Oncol. 6:286–290. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Spindler KL, Pallisgaard N, Vogelius I and Jakobsen A: Quantitative cell-free DNA, KRAS, and BRAF mutations in plasma from patients with metastatic colorectal cancer during treatment with cetuximab and irinotecan. Clin Cancer Res. 18:1177–1185. 2012.

15 

van der Drift MA, Hol BE, Klaassen CH, et al: Circulating DNA is a non-invasive prognostic factor for survival in non-small cell lung cancer. Lung Cancer. 68:283–287. 2010.PubMed/NCBI

16 

Nygaard AD, Garm Spindler KL, Pallisgaard N, Andersen RF and Jakobsen A: The prognostic value of KRAS mutated plasma DNA in advanced non-small cell lung cancer. Lung Cancer. 79:312–317. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Punnoose EA, Atwal S, Liu W, et al: Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clin Cancer Res. 18:2391–2401. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Kumar S, Guleria R, Singh V, Bharti AC, Mohan A and Das BC: Plasma DNA level in predicting therapeutic efficacy in advanced nonsmall cell lung cancer. Eur Respir J. 36:885–892. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Therasse P, Arbuck SG, Eisenhauer EA, et al: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 92:205–216. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Steffensen KD, Waldstrom M, Grove A, Lund B, Pallisgard N and Jakobsen A: Improved classification of epithelial ovarian cancer: results of 3 danish cohorts. Int J Gynecol Cancer. 21:1592–1600. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Sozzi G, Conte D, Mariani L, et al: Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients. Cancer Res. 61:4675–4678. 2001.PubMed/NCBI

22 

Kumar S, Guleria R, Singh V, Bharti AC, Mohan A and Das BC: Efficacy of circulating plasma DNA as a diagnostic tool for advanced non-small cell lung cancer and its predictive utility for survival and response to chemotherapy. Lung Cancer. 70:211–217. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Dowler Nygaard A, Spindler KG, Pallisgaard N, Andersen RF and Jakobsen A: Levels of cell-free DNA and plasma KRAS during treatment of advanced NSCLC. Oncol Rep 31: 969-974, 2014.
APA
Dowler Nygaard, A., Spindler, K.G., Pallisgaard, N., Andersen, R.F., & Jakobsen, A. (2014). Levels of cell-free DNA and plasma KRAS during treatment of advanced NSCLC. Oncology Reports, 31, 969-974. https://doi.org/10.3892/or.2013.2906
MLA
Dowler Nygaard, A., Spindler, K. G., Pallisgaard, N., Andersen, R. F., Jakobsen, A."Levels of cell-free DNA and plasma KRAS during treatment of advanced NSCLC". Oncology Reports 31.2 (2014): 969-974.
Chicago
Dowler Nygaard, A., Spindler, K. G., Pallisgaard, N., Andersen, R. F., Jakobsen, A."Levels of cell-free DNA and plasma KRAS during treatment of advanced NSCLC". Oncology Reports 31, no. 2 (2014): 969-974. https://doi.org/10.3892/or.2013.2906
Copy and paste a formatted citation
x
Spandidos Publications style
Dowler Nygaard A, Spindler KG, Pallisgaard N, Andersen RF and Jakobsen A: Levels of cell-free DNA and plasma KRAS during treatment of advanced NSCLC. Oncol Rep 31: 969-974, 2014.
APA
Dowler Nygaard, A., Spindler, K.G., Pallisgaard, N., Andersen, R.F., & Jakobsen, A. (2014). Levels of cell-free DNA and plasma KRAS during treatment of advanced NSCLC. Oncology Reports, 31, 969-974. https://doi.org/10.3892/or.2013.2906
MLA
Dowler Nygaard, A., Spindler, K. G., Pallisgaard, N., Andersen, R. F., Jakobsen, A."Levels of cell-free DNA and plasma KRAS during treatment of advanced NSCLC". Oncology Reports 31.2 (2014): 969-974.
Chicago
Dowler Nygaard, A., Spindler, K. G., Pallisgaard, N., Andersen, R. F., Jakobsen, A."Levels of cell-free DNA and plasma KRAS during treatment of advanced NSCLC". Oncology Reports 31, no. 2 (2014): 969-974. https://doi.org/10.3892/or.2013.2906
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team