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Publications (2)10.88 Total impact

  • Article: Potential clinical significance of a plasma-based KRAS mutation analysis in patients with advanced non-small cell lung cancer.
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    ABSTRACT: Non-small cell lung cancer (NSCLC) with KRAS mutation may be resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). This study aims to evaluate a plasma-based KRAS mutation analysis and the clinical significance of plasma KRAS mutation as a predictive marker for tumor resistance to EGFR-TKIs in patients with NSCLC. DNA extracted from plasma and matched tumor tissues were obtained from 273 patients with advanced stage NSCLC. Patients were followed up prospectively for treatment outcomes. KRAS mutations in codon 12 and 13 were detected using PCR-restriction fragment length polymorphism. Mutations in plasma and matched tumors were compared. Associations between KRAS mutation status and patients' clinical outcomes were analyzed. KRAS mutation was found in 35 (12.8%) plasma samples and 30 (11.0%) matched tumor tissues. The consistency of KRAS mutations between plasma and tumors is 76.7% (23 of 30; kappa = 0.668; P < 0.001). Among 120 patients who received EGFR-TKI treatment, the response rate was only 5.3% (1 of 19) for patients with plasma KRAS mutation compared with 29.7% for patients with no KRAS mutation in plasma DNA (P = 0.024). The median progression-free survival time of patients with plasma KRAS mutation was 2.5 months compared with 8.8 months for patients with wild-type KRAS (P < 0.001). KRAS mutation in plasma DNA correlates with the mutation status in the matched tumor tissues of patients with NSCLC. Plasma KRAS mutation status is associated with a poor tumor response to EGFR-TKIs in NSCLC patients and may be used as a predictive marker in selecting patients for such treatment.
    Clinical Cancer Research 02/2010; 16(4):1324-30. · 7.74 Impact Factor
  • Article: EGFR mutations are associated with prognosis but not with the response to front-line chemotherapy in the Chinese patients with advanced non-small cell lung cancer.
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    ABSTRACT: The study aimed to investigate associations of tumor tissue EGFR mutations with response to the front-line chemotherapy and prognosis in advanced non-small cell lung cancer (NSCLC) patients. EGFR genotypes of 145 chemotherapy-naive patients with Stage IIIB and IV NSCLC were examined by using denaturing high-performance liquid chromatography (DHPLC). All patients received the front-line chemotherapy. There were 69 patients who received gefitinib therapy (32 as second-line and 37 as third-line therapy). About 37.9% (55/145) of the patients was detected to have EGFR mutations in their tumor tissue DNA. The response rate (RR, complete response plus partial response) to the chemotherapy for mutated EGFR carriers was 34.5% (19/55), similar to 33.3% (30/90) for wild-type EGFR carriers (P=0.881). The patients with EGFR mutations had increased median survival time and 1- and 2-year survival rate than those with wild-type EGFR (23 vs 16 months, 86.38% vs 62.64%, 38.78% vs 27.16%, P=0.0273). Among Stage IV NSCLC patients, mutated EGFR carriers had a longer progression-free survival (PFS) than wild-type EGFR carriers (5 vs 3 months, P=0.040). Cox multivariate regression analysis showed that response to the front-line chemotherapy (RR vs PD) and EGFR mutation were independent prognostic factors (HR=0.461, 95% CI: 0.271-0.783, P=0.0042; HR=0.598, 95% CI: 0.372-0.961, P=0.0335, respectively) for patients with advanced NSCLC. We conclude that EGFR mutations in the Chinese patients with advanced NSCLC were not associated with response to the front-line chemotherapy, but Stage IV NSCLC patients with mutated EGFR had a longer PFS after the front-line chemotherapy. EGFR mutation is an independent prognostic factor for Chinese advanced NSCLC.
    Lung cancer (Amsterdam, Netherlands) 06/2009; 67(3):343-7. · 3.14 Impact Factor