Residual DNA double strand breaks correlates with excess acute toxicity from radiotherapy

Abstract

Introduction: A high risk for development of severe side effects after radiotherapy may be correlated with high cellular radiosensitivity. To enhance radiation therapy efficiency a fast and reliable in-vitro test is desirable to identify radiosensitive patients. The aim of present study was to identify the mechanism of radiation induced DNA double-strand breaks (DSBs) and DSB repair kinetics on radiosensitivity and normal tissue complications caused by the radiation therapy. Materials and Methods: The study included 50 breast cancer patients. Blood samples (taken before radiotherapy) were irradiated in vitro with 1 and 2 Gy X-rays and The initial level of double-strand breaks (DSB) and repair kinetics analyzed by flow cytometric method of phosphorylation of histone H2A (γ-H2AX-assay) at 30 minutes, 3 and 24 hours. All the patients received similar tangential irradiation of the whole breast and conventional fractionation and acute normal tissue reactions were assessed by Radiation Therapy Oncology Group criteria. Results: In the in-vitro experiment repair kinetic of DSBs after 3 and 24 hours were strongly correlated with the acute skin toxicity score following irradiation (P=0.0007 and P=0.0005 respectively; Pearson's correlation test). This issue could be subject for treatment adjustment. Conclusion: Our findings strongly suggest that the measurement of DSB by performing γ- H2AX flow cytometric analysis has the potential to be developed into a clinically useful predictive assay for distinguishing the overreactors among breast cancer patients prior to the start of radiotherapy. However, further clinical trials are required to validate these biomarkers.