Oxidative-Stress Biomarkers and Pathologic Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal...

Background: Response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) varies considerably, and oxidative stress may modulate radiosensitivity. This study evaluated ischemia-modified albumin (IMA) and thiol-disulfide homeostasis as potential biochemical predictors of pathological tumor regression. Methods: A prospective observational cohort study was conducted to assess pre- and post-treatment oxidative stress biomarkers in patients with LARC receiving capecitabine-based long-course CRT. Serum IMA, native thiol, total thiol, and disulfide levels were quantified spectrophotometrically. Pathologic regression was graded according to the Modified Ryan system as good (TRG 0-1) or poor (TRG 2-3). Receiver operating characteristic (ROC) analyses, Firth-penalized logistic regression, and internal validation using cross-validation, calibration, and decision-curve analyses were performed. Results: Of 38 screened patients, 31 met eligibility criteria and completed CRT, alongside 31 matched healthy controls. Compared with controls, patients had higher baseline disulfide (15.7 ± 5.2 vs. 11.9 ± 3.1 µmol/L; p = 0.012) and IMA levels (0.886 ± 0.062 vs. 0.798 ± 0.048 ABSU; p = 0.006). Poor responders exhibited higher pre-treatment IMA (0.927 ± 0.045 vs. 0.842 ± 0.050 ABSU; p = 0.020) and disulfide levels (18.4 ± 5.2 vs. 13.0 ± 3.8 µmol/L; p = 0.012). Pre-treatment IMA demonstrated the highest predictive accuracy for poor tumor regression (AUC = 0.872; 95% CI 0.751-0.993). In multivariable Firth-penalized logistic regression, elevated baseline IMA was independently associated with poor pathological response (OR = 3.63; 95% CI 1.22-16.20; p = 0.043), whereas negative circumferential resection margin (CRM) status was independently associated with favorable regression (OR = 0.21; 95% CI 0.02-0.71; p = 0.003). The internally validated model demonstrated excellent discrimination (AUC = 0.948; 95% CI 0.866-0.966) and good calibration. Conclusions: Baseline IMA and CRM status were independently associated with pathological response after CRT in LARC. These findings suggest that oxidative-stress biomarkers may have potential value for response stratification; however, the results should be considered exploratory and require external validation in larger independent cohorts before clinical application.