Author of

• 14490

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  P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Biology, Pathology, and Molecular Testing
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 14580

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    P2.04-090 - Changes in Circulating Epidermal Growth Factor Receptor (EGFR) during Radiotherapy in Non-Small Cell Lung Cancer (NSCLC) Patients (ID 2436)

    09:30 - 09:30  |  Author(s): N. Maihle
    • Abstract

    Background:
    Epidermal growth factor receptor (EGFR) is overexpressed in a variety of malignant tumors including lung cancer. A circulating isoform of EGFR has been detected in the blood of lung cancer patients. Previous reports suggest that low baseline plasma EGFR concentrations are associated with reduced survival in patients with stage IV non-small cell lung cancer (NSCLC) post-chemotherapy. The goal of the present study was to determine whether: 1) plasma EGFR concentrations change during- and/or after radiotherapy, 2) the changes are associated with overall survival (OS) in stage I-III NSCLC following radiation treatment.
    
    Methods:
    Patients enrolled in prospective studies in which platelet poor plasma samples had been collected were eligible. All patients received radiation-based treatment. Patient age, gender, ECOG score, clinical stage, pathology, smoking history, chemotherapy and radiotherapy were all included in this analysis. Blood samples were collected pre-radiotherapy (pre-), during radiotherapy (2 weeks) (2w), during radiotherapy (4 weeks) (4w) and post-radiotherapy (more than 4 weeks post-radiotherapy). Plasma EGFR concentrations were measured using a commercial enzyme-linked immunoassay kit (BosterBio Inc., Pleasanton, CA) that detects the extracellular domain of EGFR. The primary endpoint was OS.
    
    Results:
    183 patients with median age of 66, 143 male and 40 female, were included in this study. The median OS was 15.5 months (95% confidence interval [CI]: 20.8-27.3). The mean plasma concentration of EGFR was 35.6 ng/ml for pre- (n=116, 95% CI: 33.9-37.4); 22.4 ng/ml for 2w (n=114, 95% CI: 20.8-24.0); 34.5 ng/ml for 4w (n=114, 95% CI: 31.4-37.7); and 45.0 ng/ml for post (n=114, 95% CI: 40.1-49.9). The plasma level at 2w was significantly lower than pre-levels (p < 0.01). The plasma EGFR level at 4w was significantly higher than at 2w (p < 0.01), though it was not significantly different from that of pre-RT levels. There is a significant increase in EGFR levels in post-RT treated patients (p < 0.01). Post-treatment levels are above all other points observed in cancer patients, including at baseline and during-RT. However, no significant correlation between the levels of EGFR and OS, or between the ratio 2w/pre or post/pre and OS were observed. Kaplan-Meier survival analysis showed pre- EGFR concentrations [22.2 months (95% CI: 6.8-37.7) versus 23.5 months (95% CI: 14.1-32.9) (p = 0.527)] and fold changes of 2w/pre- [24.5 months (95% CI: 11.2-35.9) versus 23.7 months (95% CI: 12.2-42.3) (p=0.928)] respectively.
    
    Conclusion:
    In parallel with previous reports for the treatment of NSCLC patients with gefitinib, RT results in a decrease in EGFR plasma concentrations shortly after therapy (2 weeks), but an increase relative to baseline levels by 4 weeks, followed by a further increase (to above baseline levels) by 3 months post-treatment. In patients treated with gefitinib, this increase correlated with worse response to therapy. Here there does not appear to be a correlation between increased plasma EGFR levels and OS following RT. The biologic mechanism(s) underlying these observations, and their clinical implications warrant further study.