Residual γH2AX foci predict local tumour control after radiotherapy

Abstract

Purpose: Evaluation of micromilieu-dependent quantified γH2AX 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 γH2AX foci) and 24 h (residual γH2AX foci) after exposure to a single dose of 4 Gy. The initial and residual normalised γH2AX 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 γH2AX foci and TCD50 SDclamp and TCD50 fx for 9 HNSCC tumour xenograft models in vivo was found. Residual normalised γH2AX foci showed higher intertumoural variability and their correlation with TCD50 was more robust.

Conclusions: For the first time a significant negative correlation between γH2AX foci and local tumour control after irradiation has been demonstrated. Our results underline the potential of residual γH2AX foci as a predictive biomarker for local tumour control after radiotherapy.

Keywords: Biomarker; DNA repair; Local tumour control; Radiotherapy; Tumour micromilieu; γH2AX.