The kinetics of γ-H2AX during radiotherapy of head and neck cancer potentially allow for prediction of severe mucositis
Purpose: The aim of the study was to evaluate the changes in γ-H2AX expression in peripheral blood lymphocytes (PBL) according to severity of radiation-induced mucositis (M) during radiotherapy.
Patients and Method:
50 patients with head and neck cancer treated withradiotherapy (RT) or chemoradiation were included in the study.Blood samples were collected before treatment to measure baseline
γ-H2AX levels for every patient. Second sample was taken 45 minutes after the first RT fraction and then once a week, 45 min after irradiation. In patients treated with chemoradiation the blood sample was taken the day after chemotherapy.
Mucositis was evaluated once a week and reported according to CTCAE v3 and 4 and RTOG/EORTC scales. PBL were analyzed with flow cytometry and level of H2AX phosphorylation (γ-H2AX) at every time point was evaluated.
In 35 patients mild to moderate mucositis was observed. 15 patients developed severe mucositis. No cases of grade 4 mucositis were observed.
The difference in baseline levels of γ-H2AX between groups with mild and severe mucositis was statistically insignificant (p= 0.25). The statistically significant difference in γ-H2AX level was observed in week 7 of treatment (p=0.01). No significant differences in γ-H2AX level were observed neither between group treated with concomitant treatment nor radiotherapy alone. In the analysis of the kinetics of γ-H2AX during treatment, a statistically significant difference (p=0.0088) between groups with mild and severe mucositis was observed. After fourth week of treatment levels of γ-H2AX decreased significantly in the group with severe mucositis and increased in patients with mild side effects. The observed difference was not caused by the decrease in of peripheral lymphocyte count, which was similar in both groups.
Based on presented results, severity of radiation-induced mucositis does not correlate directly with γ-H2AX levels measured in vivoin PBL. Prediction based on γ-H2AX level is not yet possible, either before treatment or early during treatment, but preliminary results indicating significant differences in γ-H2AX kinetics between groups encourage further studies.