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 (γ-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. γ-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. -test and repeated measures analysis of variance (ANOVA) evaluated dynamic changes in γ-H2AX levels, and a multilevel linear regression model analyzed the relationship between γ-H2AX levels and treatment response.

RESULTS

Nineteen out of thirty patients (63.33%) were classified as responders. Significant dynamic changes in γ-H2AX levels were observed between non-responders and responders (P=0.01). The multilevel linear regression model showed a trend towards increased γ-H2AX levels in responders [1.17, 95% confidence interval (CI): -0.02 to 2.34, P=0.053]. Significant differences in γ-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 γ-H2AX ratios compared to those without pCR (P=0.04). However, no significant difference was identified in the multilevel linear regression model.

CONCLUSIONS

γ-H2AX may have potential as a biomarker for treatment response in locally advanced rectal cancer patients undergoing preoperative CCRT, although further validation is required.