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Z. Chen



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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-003 - Clinical significance of detection of EGFR and KRAS mutations in plasma/pleural effusion in patients with advanced NSCLC (ID 189)

      09:30 - 09:30  |  Author(s): Z. Chen

      • Abstract

      Background
      In this study, we attempted to detect EGFR and KRAS mutations in plasma/pleural effusion of patients with advanced NSCLC by pyrosequencing, to investigate whether plasma and pleural effusion DNA could be used as a substitute for tumor tissues for detecting gene mutations, and to explore the correlation of EGFR/KRAS mutations with the efficacy of the epithelial growth factor receptor-tyrosine kinase inhihitor (EGFR-TKI) as well as their correlation with survival in TKI-treated patients.

      Methods
      Blood, pleural effusion and tumor tissues were obtained from 146, 64 and 63 patients with advanced NSCLC, of whom there were 40 matched tissue and plasma samples, 24 matched tissue and pleural effusion samples. The exons 19, 20 and 21 of EGFR was amplified by mutant-enriched PCR using selective restriction enzyme digestion, and exon 2 of KRAS in plasma were amplified by nested-PCR. Then mutations were detected by pyrosequencing. The association between mutations and the patients’ survival was analyzed using Kaplan-Meier.

      Results
      EGFR mutations were detected in 34.38% tissues (22/64), 24.24% plasma samples (24/96) and 30.16% pleural effusion samples(19/63). KRAS mutations were detected in 4.69% tissues (3/64), 6.16% plasma samples (9/146) and 7.93% pleural effusion samples. No statistical significance was found in EGFR/KRAS mutations between plasma/pleural effusion and tumor tissues (p>0.05). The same EGFR genes were observed in plasma and matched tissue in 34 patients (consistency: 85%).The sensitivity of detecting EGFR mutations is 73.33% and the specificity is 92 %.There was only 1 KRAS mutation detected in the 40 tissues , but no mutation in the matched plasma (consistency: 97.5%). Same EGFR/KRAS genes were observed in 21, 23 pleural effusion and matched tissue respectively (consistency: 87.5%, 95,83%). The sensitivity of detection of EGFR/KRAS mutations is 77.78% and 66.67%. The specificity is 93.33 % and 100%. Significant correlation existed between EGFR mutations in tumor tissue/pleural effusion from patients with advanced NSCLC, and a smoking history, and histopathologic type (p<0.05). Among the 38 TKI-treated patients, the disease control rate (DCR) and objective response rate (ORR) were 90% and 60%, respectively, in patients with EGFR mutation in plasma, and 53.57% and 17.86%, respectively, in patients with wide-type EGFR (DCR, p=0.059; ORR, p=0.019).The DCR and ORR were 66.67% and 33.33%, respectively, in patients with wide-type KRAS in plasma, and 40% and 0%, respectively, in patients with KRAS mutation. Patients with EGFR activating mutations in plasma had a favoring median PFS of 10.5 months, significantly longer than the patients with wild-type EGFR (5.0 months) (p=0.228). The median PFS was 2.5 months for patients with KRAS mutation and 9 months for patients with wild-type KRAS, respectively (p=0.000).

      Conclusion
      A high consistency exists between EGFR/KRAS mutation detection in plasma/pleural effusion and tumor tissues. Plasma/pleural effusion could be used as a substitute for tumor tissues for detecting gene mutations. EGFR and KRAS mutations in plasma are highly associated with the treatment response and prognosis of TKI-treated patients. It is feasible to detect EGFR and KRAS mutations in plasma/pleural effusion by pyrosequencing. The detection sensibility of EGFR mutations can be increased by ME-PCR, facilitating choosing patients for TKI treatment.