Author of

• 11543

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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
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11594

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    P2.06-051 - Clinical significance of pretreatment plasma biomarkers in advanced non-small cell lung cancer patients (ID 1160)

    09:30 - 09:30  |  Author(s): D. Wu
    • Abstract

    Background
    The use of biomarkers for selecting patients with non-small cell lung cancer (NSCLC) for treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is essential for achieving a satisfactory therapeutic outcome. EGFR mutations have been found to be predictive of response to EGFR-TKIs. The aim of this study was to explore whether biomarkers which can be identified in plasma, such as EGFR mutations, circulating free DNA, and levels of expressed cytokines are predictive for response to EGFR-TKIs and patient survival time.

    Methods
    Formalin-fixed and paraffin-embedded biopsies from tumor tissues and paired plasma samples were collected from 134 patients with advanced NSCLC, EGFR mutations in both types of specimens were assessed by an ARMS/Scorpion assay using real-time PCR. Expression levels of transforming growth factor-alpha and beta one (TGF-α and TGF-β1) were assessed using an enzyme-linked immunosorbent assay (ELISA). Concentrations of circulating free DNA were detected in both NSCLC patients and healthy subjects by a colorimetric assay using ultraviolet spectrometry. The clinical significance of EGFR mutations, levels of cytokines, and circulating free DNA was assessed in advanced NSCLC patients treated with EGFR-TKIs.

    Results
    EGFR somatic mutations were detected in the tumors from 68 of 134 (50.7%) advanced NSCLC patients, and EGFR mutations were detected in the plasma samples from 17 (12.7%) NSCLC patients. Also, the concentrations of circulating free DNA were higher in NSCLC patients than in healthy subjects (P<0.01). EGFR-TKI treatment produced significant effects on progression-free survival (PFS) and overall survival (OS) that were related to the presence of EGFR mutations detected in the tumor tissues (P<0.01).Patients with high levels of TGF-β1 showed shorter OS and worse response to EGFR-TKI treatment than patients with low TGF-β1 levels (P<0.01); however, patients with different expression levels of TGF-α showed no difference in either PFS or OS (P>0.05). Multivariate analysis showed that younger age, adenocarcinoma, never smoking and EGFR somatic mutation were associated with a longer PFS time, and adenocarcinoma, never smoking, low performance status (PS) score, EGFR somatic mutation and low levels of TGF-β1 were associated with greater OS (P<0.05).

    Conclusion
    Plasma levels of TGF-β1 may be a marker for predicting response to EGFR-TKIs and survival time in NSCLC patients, and levels of circulating free DNA could be a biomarker for differentiating between NSCLC patients and healthy individuals.