Poster Presentation 25th Lorne Cancer Conference 2013

DNA Damage Response in Peripheral Blood Lymphocytes and Out-of-Field Hair Follicles During Radiotherapy of Patients with Non-Small Cell Lung Cancer: A Prospective Clinical Trial (#356)

Shankar Siva 1 2 , Jai Smith 1 , Thomas Devereux 1 , Tomas Kron 1 , Richard A Cox 1 , David L Ball 1 , Michael P MacManus 1 , Pavel Lobachevsky 1 , Olga A Martin 1
  1. Peter MacCallum Cancer Centre, Melbourne East, VIC, Australia
  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia

Introduction and Purpose:- Radiotherapy is the standard of care for locally advanced non-small cell lung carcinoma (NSCLC). At present the interactions between radiation dose, toxicity and systemic responses are poorly understood. The purpose of this study was to monitor DNA damage using the gamma-H2AX assay in tissues inside and outside irradiated volumes of 10 patients with NSCLC.

Materials and Methods:- Radiotherapy was planned to 60 Gy in 30 fractions over 6 weeks, delivered with or without platinum chemotherapy. The number, distribution and kinetics of gamma-H2AX foci were compared with the irradiated volume and treatment factors. Lymphocytes and eyebrow hairs were fixed and 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 and Conclusions:- The irradiated target volume ranged between 87-1137 cm3. We observed the presence of a small subpopulation of lymphocytes with multiple (>5) gamma-H2AX foci at 1-hour post-first fraction. There was a strong correlation between the size of this subpopulation and irradiated volume (r=0.86, 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, observed hair follicle gamma-H2AX foci were similar to baseline at 1-hour post first-fraction, elevated at 24 hrs, generally elevated at 4 weeks but reduced at 3 months. The scattered dose at the eyebrow was recorded at <0.005Gy per fraction and was insufficient to directly induce the observed gamma-H2AX signal. To our knowledge, this is the first report of abscopal DNA damage response in hair follicles associated with radiotherapy in cancer patients.

Disclosures:- Nil relevant disclosures