Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

L. Tang



Author of

  • +

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
    • +

      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): L. Tang

      • 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.

  • +

    P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      P2.11-043 - Analysis of clinicopathological features for Chinese patients with advanced non-small cell lung cancer harboring EML4-ALK fusion genes (ID 2968)

      09:30 - 09:30  |  Author(s): L. Tang

      • Abstract

      Background
      The echinoderm microtubule-associated protein like-4—anaplastic lymphoma kinase (EML4--ALK) fusion oncogene defines a novel molecular subset of non-small cell lung cancer (NSCLC). Crizotinib (Xalkori) has been approved for patients with locally advanced or metastatic NSCLC that is ALK positive. However, the clinicopathological characteristics of patients with the EML4-ALK gene have not been identified completely.

      Methods
      The clinicopathological characteristics of 200 Chinese patients with advanced NSCLC were analyzed retrospectively．Clinical factors including age, sex, smoking history, pathological type, biopsy method, site of biopsy and interval between biopsy and the identification of EML4-ALK fusions and the status of epidermal growth factor receptor (EGFR) mutation were analyzed to investigate possible correlations with EML4-ALK fusions.

      Results
      Among the 200 patients with NSCLC enrolled, 56 (28.0%) harbored the EML4-ALK gene in this retrospective study. EML4-ALK fusions could not be detected in 22 of 200 patients (11.0%) because of insufficient tissue. The median age was 53 as a whole. The median ages of ALK positive and negative groups were 48 and 55 years, respectively. Patients with the EML4-ALK gene were significantly younger than patients without EML4-ALK (p＜0.001). The detection rate of EML4-ALK rearrangement in patients with tumor or metastatic lymph nodes resection was significantly higher than patients with needle biopsy(p=0.003). If the interval between biopsy and the identification of EML4-ALK fusions was less than 48 months, the detection rate of EML4-ALK rearrangement was significantly higher compared with the interval more than 48months(p=0.020). Among the 200 patients, 103(51.5%) patients had received EGFR mutation detection. Only 1 case harbored both EML4-ALK rearrangement and EGFR mutations. The incidence of EML4-ALK rearrangement in patients with EGFR wide type（42.5%,37/87）was significantly higher than EGFR mutant type（6.3%,1/16）. No significant difference in the distribution of sex, smoking history, pathological type, and site of biopsy(lung tumor compared with metastatic lymph nodes) was observed between ALK positive and negative groups (p = 0.140, 0.103, 0.438 and 0.217, respectively).

      Comparisons of patient characteristics according to genotype
      EML4-ALK gene
      Characteristics Total,n Positive,n Negative,n P value
      56 122
      Age(years)
      Median 53 48 55 ＜0.001
      Range 25-76 25-74 27-76
      Sex
      Male 78 20 58 0.140
      Female 100 36 64
      Smoking history
      Never/light smokers 143 49 94 0.103
      Smokers 35 7 28
      Pathological type
      Adenocarcinoma 161 52 109 0.438
      Non- adenocarcinoma 17 4 13
      Biopsy method
      Tumor and metastatic lymph nodes resection 158 49 109 0.003
      Needle biopsy 20 7 13
      Site of biopsy
      Lung tumor 99 27 72 0.217[$]
      Metastatic lymph nodes 72 26 46
      Pleura 2 1 1
      Others 5 2 3
      Interval between biopsy and the identification of EML4-ALK fusions (months)
      ≤48 167 55 112 0.020
      ＞48 11 1 10
      EGFR mutation(n=103)
      Mutant type 16 1 15 0.005
      Wide type 87 37 50
      $:lung tumor compared with lymph nodes

      Conclusion
      We identified younger age and EGFR wide type as clinicopathological features of patients with advanced NSCLC harboring EML4-ALK fusion genes. The detection rate of EML4-ALK rearrangement was significantly higher in patients with tumor or metastatic lymph nodes resection and the interval less than 48 months between biopsy and the identification of EML4-ALK fusions.