Predictive value of oxidative DNA damage biomarker (8-hydroxy-2’-deoxyguanosine) for the response to neoadjuvant chemoradiation therapy in locally advanced rectal cancer

Burlaka A.A., Kolesnik O.O., Michailovich Y.I.

Summary. Introduction. Overall, locally advanced rectal cancer (LARC) accounts for 5–22% of all rectal cancers, with sphincter-preserving surgery unachievable in more than 30% of the patients. A promising direction for potential improvement in efficacy of the combined LARC treatment is modification the regimen’s neoadjuvant chemotherapy (NCT), namely the fluoropyrimidine monotherapy replacement on polychemotherapy including capecitabine plus oxaliplatin (CAPOX) regimen. 8-hydroxy-2’-deoxyguanosine (8-oxo-dGuo) is one of the most abundant by-products of oxidatively damaged DNA and the marker for oxidative stress. In repair absence being present in the DNA, 8-oxo-dGuo is capable of causing cell-cycle arrest and apoptosis. 8-oxo-dGuo can accumulate both in nuclear and in mitochondrial DNA, for this very reason it is considered a highly informative marker for the occurrence of malignancies and one of the important markers of tumour response to systemic treatment. Material and methods. Taking into account a neoadjuvant chemoradiation therapy (nCRT) protocol, patients diagnosed with distal LARC were randomized in 1:1 ratio. Patients in the main group (n=57) received radiotherapy (RT) with total radiation dose of 50.4 Gy in 28 sessions (1.8 Gy per session). Simultaneously with RT, our patients were undergoing polychemotherapy (PCT) which included CAPOX regimen (2 cycles). Patients in the comparison group (n=53) were stratified by the total radiation dose of 50.4 Gy (1.8 Gy/daily) inside 28 sessions in combination with concurrent capecitabine-based monochemotherapy (MCT) (2 cycles). Levels of 8-oxo-dGuo were determined in peripheral blood before and after nCRT. Results. The mean value of 8-oxo-dGuо after nCRT significantly exceeded the physiological range, which is an average of 0.23±0.04 nmol/ml•min. The obtained data also showed that there was no significant difference in the level of oxidative DNA damage between the studied groups (3.07±0.08 nmol/ml•min in the main group vs 2.94±0.06 nmol/ml•min in the comparison group). However, the mean blood values of 8-oxo-dGuo in the main and comparison groups after the nCRT completion were 1.96±0.04 nmol/ml•min and 2.72±0.04 nmol/ml•min, respectively (p<0.001). Statistical analysis for determine levels’ reducing 8-oxo-dGuо, in case used of CAPOX-based PCT regimen may be an independent marker in determining the chemo-radiation therapy effectiveness in combined treatment LARC patients (R2=0.465; 95% CI 0.004–0.016, p<0.0001). Conclusions. Our study suggests that assessment of 8-oxo-dGuо levels in neutrophils of peripheral blood patients with LARC can be used as a marker for predicting the pathologic response on nCRT.
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