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• 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

  • 11579

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    P2.06-036 - DNA Damage Response during Curative Radiotherapy of Non-Small Cell Lung Cancer: In-Vivo Biodosimetry with Peripheral Blood Lymphocytes and Systemic Effects Measured in Hair Follicles (ID 2652)

    09:30 - 09:30  |  Author(s): P. Lobachevsky
    • Abstract

    Background
    The interactions between radiation dose, toxicity and systemic responses are poorly understood during radiotherapy of patients with NSCLC). The purpose of this study was to monitor DNA damage using the gamma-H2AX assay in tissues inside and outside irradiated volumes of patients with NSCLC.

    Methods
    This prospective ethics approved study assessed 12 patients receiving radiotherapy was planned to 60 Gy in 30 fractions over 6 weeks. Six patients receive concurrent platinum doublet chemotherapy (chemoRT), and six patients had radiotherapy alone. The number, distribution and kinetics of gamma-H2AX foci were compared with the irradiated volume. Lymphocytes and eyebrow hairs were processed for gamma-H2AX staining and microscopy at each of 5 time-points; baseline, 1 and 24 hours post-first fraction, 4 weeks into radiotherapy, and 3 months after treatment completion.

    Results
    The mean irradiated target volume was 384 cm[3] (range 87-1137 cm[3]). We observed the presence of a small subpopulation of lymphocytes with multiple (>5) gamma-H2AX foci at 1-hour post-first fraction. There was no difference in this subpopulation between patients receiving chemoradiotherapy or radiotherapy alone at baseline (p=0.26) nor at 1-hour (p=0.24) There was a strong correlation between the size of this subpopulation and irradiated volume (r=0.84, p<0.01), indicating direct radiation exposure. This suggests potential utility of the gamma-H2AX assay as a human in-vivo biodosimeter. This subpopulation was not detected at 24 hours due to DNA damage repair. A trend for reduction of this subpopulation and the average number of foci in lymphocytes analysed at 4 weeks of radiotherapy suggests an impaired radiation response after multiple radiotherapy fractions. By contrast, the mean number of observed hair follicle gamma-H2AX foci was not different from baseline to 1-hour post first-fraction (p=0.42), elevated at 24 hrs (p=0.10) and 4 weeks (p=<0.01) but was not different from baseline at 3 months (p=0.31). The scattered dose at the eyebrow was recorded at <0.01 Gy per fraction and was insufficient to directly induce the observed gamma-H2AX signal Figure 1 Figure 1 - a brisk DNA damage response in out-of-field eyebrow hair 24-hours post radiation (gamma-H2AX foci in green)

    Conclusion
    The Gamma-H2AX assay on peripheral blood at 1-hour may be a useful as a human in-vivo biodosimeter. To our knowledge, this study is the first report of abscopal DNA damage response in hair follicles associated with radiotherapy in cancer patients. Further validation of our findings on a larger patient cohort is warranted.