Residual γH2AX foci predict local tumour control after radiotherapy

Purpose: Evaluation of micromilieu-dependent quantified gamma H2AX foci as a potential predictive biomarker in well-oxygenated tumour areas in 9 HNSCC xenograft models in vivo. Materials & methods: GammaH2AX foci were quantified in perfused tumour areas 30 min (initial gamma H2AX foci) and 24 h (residual gamma H2AX foci) after exposure to a single dose of 4 Gy. The initial and residual normalised gamma H2AX foci were correlated with TCD50 after single dose irradiation under clamped blood flow (SDclamp) or a fractionated irradiation setting under ambient blood flow (fx). Results: A significant negative correlation between initial and residual normalised gamma H2AX foci and TCD50 SDclamp and TCD50 fx for 9 HNSCC tumour xenograft models in vivo was found. Residual normalised gamma H2AX foci showed higher intertumoural variability and their correlation with TCD50 was more robust. Conclusions: For the first time a significant negative correlation between gamma H2AX foci and local tumour control after irradiation has been demonstrated. Our results underline the potential of residual gamma H2AX foci as a predictive biomarker for local tumour control after radiotherapy. (C) 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 108 (2013) 434-439