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Insufficiency of peripheral blood as a substitute tissue for detecting EGFR mutations in lung cancer: a meta-analysis

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Abstract

The detection of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer tissues is necessary for effective treatment with EGFR tyrosine kinase inhibitors. However, tumor tissues may not be available in all situations. Studies have evaluated the potential use of serum or plasma for detecting the EGFR mutation status, but the results have been inconclusive. Here, a meta-analysis was performed to determine whether blood samples could serve as substitutes for tissue specimens in detecting the EGFR mutation status. Databases, including PubMed and Embase, were searched for relevant studies published from 2005 to 2013 that included true-positive, false-positive, true-negative, and false-negative values of the EGFR mutation status of the blood compared with tissue specimens. Summary receiver operating characteristic curves were developed to explore the threshold effect. Spearman’s correlation coefficient was calculated to analyze the heterogeneity between studies. Pooled sensitivity and specificity were evaluated using Meta-DiSc version 1.4. Thirteen articles involving 1,591 cases were enrolled, with a pooled sensitivity and specificity of 64.5 % (95 % CI = 0.605–0.683) and 88.5 % (95 % CI = 0.863–0.904), respectively. Heterogeneity among the studies was caused by factors other than threshold effect. The findings were influenced by test method (p = 0.0354). Blood samples had a high specificity and relatively low sensitivity for detecting EGFR mutations compared to tumor tissues. The results of this meta-analysis suggest that peripheral blood is insufficient as a substitute for tumor tissues in detecting EGFR mutations in clinical practice.

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References

  1. Siegel R, Naishadh D, Jemal A (2013) Cancer statistics. CA Cancer J Clin 63:11–30

    Article  PubMed  Google Scholar 

  2. Pao W, Chmielecki J (2010) Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nat Rev Cancer 10:760–774

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Molina JR, Yang P, Cassivi SD et al (2008) Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 83:584–594

    Article  PubMed Central  PubMed  Google Scholar 

  4. Schiller JH, Harrington D, Belani CP et al (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92–98

    Article  CAS  PubMed  Google Scholar 

  5. Scagliotti GV, Selvaggi G, Novello S, et al. The biology of epidermal growth factor receptor in lung cancer. Clin Cancer Res 2004;10:4227 s-4232s.

    Google Scholar 

  6. Fujino S, Enokibori T, Tezuka N et al (1996) A comparison of epidermal growth factor receptor levels and other prognostic parameters in non-small cell lung cancer. Eur J Cancer 32A:2070–2074

    Article  CAS  PubMed  Google Scholar 

  7. Shepherd FA, Rodrigues Pereira J, Ciuleanu T et al (2005) Erlotinib in previously treated non-small cell lung cancer. N Engl J Med 353:123–132

    Article  CAS  PubMed  Google Scholar 

  8. Bell DW, Lynch TJ, Haserlat SM et al (2005) Epidermal growth factor receptor mutations and gene amplification in non-small cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. J Clin Oncol 23:8081–8092

    Article  CAS  PubMed  Google Scholar 

  9. Chen G, Feng J, Zhou C et al (2013) Quality of life (QoL) analyses from OPTIMAL (CTONG-0802), a phase III, randomised, open-label study of first-line erlotinib versus chemotherapy in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). Ann Oncol 24:1615–1622

    Article  CAS  PubMed  Google Scholar 

  10. Rosell R, Carcereny E, Gervais R et al (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13:239–246

    Article  CAS  PubMed  Google Scholar 

  11. Paez JG, Jänne PA, Lee JC et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500

    Article  CAS  PubMed  Google Scholar 

  12. Sequist LV, Martins RG, Spigel D et al (2008) First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations. J Clin Oncol 26:2442–2449

    Article  CAS  PubMed  Google Scholar 

  13. Costa DB, Kobayashi S, Tenen DG et al (2007) Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers. Lung Cancer 58:95–103

    Article  PubMed Central  PubMed  Google Scholar 

  14. Sozzi G, Conte D, Leon M et al (2003) Quantification of free circulating DNA as a diagnostic marker in lung cancer. J Clin Oncol 21:3902–3908

    Article  CAS  PubMed  Google Scholar 

  15. He C, Liu M, Zhou C et al (2009) Detection of epidermal growth factor receptor mutations in plasma by mutant-enriched PCR assay for prediction of the response to gefitinib in patients with non-small-cell lung cancer. Int J Cancer 125:2393–2399

    Article  CAS  PubMed  Google Scholar 

  16. Brevet M, Johnson ML, Azzoli CG et al (2011) Detection of EGFR mutations in plasma DNA from lung cancer patients by mass spectrometry genotyping is predictive of tumor EGFR status and response to EGFR inhibitor. Lung Cancer 73:96–102

    Article  PubMed Central  PubMed  Google Scholar 

  17. Mack PC, Holland WS, Burich RA et al (2009) EGFR mutations detected in plasma are associated with patient outcomes in erlotinib plus docetaxel-treated non-small cell lung cancer. J Thorac Oncol 4:1466–1472

    Article  PubMed  Google Scholar 

  18. Yung TK, Chan KC, Mok TS et al (2009) Single-molecule detection of epidermal growth factor receptor mutations in plasma by microfluidics digital PCR in non-small cell lung cancer patients. Clin Cancer Res 15:2076–2084

    Article  CAS  PubMed  Google Scholar 

  19. Kimura H, Suminoe M, Kasahara K et al (2007) Evaluation of epidermal growth factor receptor mutation status in serum DNA as a predictor of response to gefitinib (IRESSA). Br J Cancer 97:778–784

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Bai H, Mao L, Wang HS et al (2009) Epidermal growth factor receptor mutations in plasma DNA samples predict tumor response in Chinese patients with stages IIIB to IV non–small-cell lung cancer. J Clin Oncol 27:2653–2659

    Article  CAS  PubMed  Google Scholar 

  21. Kim ST, Sung JS, Jo UH et al (2013) Can mutations of EGFR and KRAS in serum be predictive and prognostic markers in patients with advanced non-small cell lung cancer (NSCLC)? Med Oncol 30:328

    Article  PubMed  Google Scholar 

  22. Huang Z, Wang ZJ, Bai H et al (2012) The detection of EGFR mutation status in plasma is reproducible and can dynamically predict the efficacy of EGFR-TKI. Thoracic Cancer 3:334–340

    Article  Google Scholar 

  23. Zhao X, Han RB, Zhao J et al (2013) Comparison of epidermal growth factor receptor mutation statuses in tissue and plasma in stage I-IV non-small cell lung cancer patients. Respiration 85:119–125

    Article  CAS  PubMed  Google Scholar 

  24. Song GH, Ren J, Zhang LJ et al (2010) Low correspondence of EGFR mutations in tumor tissue and paired serum of non-small-cell lung cancer patients. Chin J Cancer Res 22:27–31

    Article  CAS  Google Scholar 

  25. Ellison G, Zhu G, Moulis A et al (2013) EGFR mutation testing in lung cancer: a review of available methods and their use for analysis of tumour tissue and cytology samples. J Clin Pathol 66:79–89

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Jiang B, Liu F, Yang L et al (2011) Serum detection of epidermal growth factor receptor gene mutations using mutant-enriched sequencing in Chinese patients with advanced non-small cell lung cancer. J Int Med Res 39:1392–1401

    Article  CAS  PubMed  Google Scholar 

  27. Kim ST, Jung HY, Sung JS et al (2013) Can serum be used for analyzing the EGFR mutation status in patients with advanced non-small cell lung cancer? Am J Clin Oncol 36:57–63

    Article  CAS  PubMed  Google Scholar 

  28. Hu C, Liu X, Chen Y et al (2012) Direct serum and tissue assay for EGFR mutation in non-small cell lung cancer by high-resolution melting analysis. Oncol Rep 28:1815–1821

    CAS  PubMed  Google Scholar 

  29. Goto K, Ichinose Y, Ohe Y et al (2012) Epidermal growth factor receptor mutation status in circulating free DNA in serum: from IPASS, a phase III study of gefitinib or carboplatin/paclitaxel in non-small cell lung cancer. J Thorac Oncol 7:115–121

    Article  CAS  PubMed  Google Scholar 

  30. Kimura H, Kasahara K, Kawaishi M et al (2006) Detection of epidermal growth factor receptor mutations in serum as a predictor of the response to gefitinib in patients with non-small-cell lung cancer. Clin Cancer Res 12:3915–3921

    Article  CAS  PubMed  Google Scholar 

  31. Kuang Y, Rogers A, Yeap BY et al (2009) Noninvasive detection of EGFR T790M in gefitinib or erlotinib resistant non-small cell lung cancer. Clin Cancer Res 15:2630–2636

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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The authors declare that they have no conflict of interest.

Funded by

Zhejiang Provincial Traditional Chinese Medicine Foundation for Outstanding Young Talent (no. 2012ZQ005).

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Correspondence to Yongjun Zhang.

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Li, Z., Zhang, Y., Bao, W. et al. Insufficiency of peripheral blood as a substitute tissue for detecting EGFR mutations in lung cancer: a meta-analysis. Targ Oncol 9, 381–388 (2014). https://doi.org/10.1007/s11523-014-0312-2

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  • DOI: https://doi.org/10.1007/s11523-014-0312-2

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