Baseline γH2AX foci, 53BP1 values and late morbidity after definitive radio-chemotherapy in head and neck carcinoma patients

Abstract

Purpose: Can double strand breaks in peripheral lymphocytes measured as baseline γH2AX and 53BP1 values be used as a signal for reduced DNA repair capacity and an increased late radiation morbidity? Methods and materials: Of 357 patients, homogenously treated with a definitive radio-chemotherapy, 11 patients without any relevant comorbidity concerning baseline DNA double strand breaks, a follow up of more than 3.5 years and different levels of late morbidity were selected. γH2AX and 53BP1 foci were analyzed, using the fully automated AKLIDES ® system (Medipan). For foci detection, images of different z-planes throughout the nucleus were obtained. For further evaluation mean focus number/cell as well as percentage of γH2AX/ 53BP1 focus-positive cells were used. Results: Patients with late toxicity levels 0°, I° and III° showed median numbers of γH2AX foci per peripheral mononuclear cell of 0.26, 0.34 and 0.73 respectively. The corresponding median values of 53BP1 foci per cell were 0.13, 0.06 and 0.40, respectively and concordant percentages of γH2AX positive cells for the 3 different late toxicity groups were 10.85, 14.30 and 30.67 as well as of 53BP1 positive cells 8.5, 5.7 and 25.37, respectively. Despite the wide interindividual range of all values, patients with severe late morbidity showed increased values for γH2AX as well as 53BP1 foci compared to the other groups, whereas no differences between groups with no or mild toxicity were seen. Conclusions: The determination of baseline γH2AX foci in peripheral blood mononuclear cells could be suited as a marker for late morbidity after definitive radio-chemotherapy of head and neck carcinoma. Blood sampling at the time of treatment i.e. moment of origin of the late effect should be more effective rather than a retrospective study. To address this question a prospective trial with a larger cohort of patients and a long term follow up is needed.