Changing of gamma-H2AX in peripheral blood mononuclear cells during concurrent chemoradiation in locally advanced rectal cancer patients: a potential response predictor

Background: The most detrimental effect of DNA damage from radiation is DNA double-strand breaks, making it critical to identify reliable biomarkers for treatment response in cancer therapy. Gamma-H2AX (gamma-H2AX), a marker of DNA double-strand breaks, was evaluated in this study as a potential biomarker for treatment response in locally advanced rectal cancer patients undergoing preoperative concurrent chemoradiation (CCRT). Methods: Thirty patients with locally advanced rectal cancer received preoperative CCRT. Peripheral blood mononuclear cells (PBMCs) were collected at five time points: baseline, 24 hours after the first radiation fraction, mid-treatment, end of treatment, and six weeks post-CCRT. gamma-H2AX levels were measured in these samples. MRI was used to assess treatment response based on magnetic resonance tumor regression grade (mrTRG). Patients were classified as responders or non-responders based on mrTRG. T-test and repeated measures analysis of variance (ANOVA) evaluated dynamic changes in gamma-H2AX levels, and a multilevel linear regression model analyzed the relationship between gamma-H2AX levels and treatment response. Results: Nineteen out of thirty patients (63.33%) were classified as responders. Significant dynamic changes in gamma-H2AX levels were observed between non-responders and responders (P=0.01). The multilevel linear regression model showed a trend towards increased gamma-H2AX levels in responders [1.17, 95% confidence interval (CI): -0.02 to 2.34, P=0.053]. Significant differences in gamma-H2AX levels were observed from baseline to mid-treatment, end of treatment, and six weeks post-CCRT. Pathologic complete response (pCR) after CCRT was associated with significantly higher gamma-H2AX ratios compared to those without pCR (P=0.04). However, no significant difference was identified in the multilevel linear regression model. Conclusions:gamma-H2AX may have potential as a biomarker for treatment response in locally advanced rectal cancer patients undergoing preoperative CCRT, although further validation is required