The adoption of neoadjuvant concurrent chemoradiotherapy (CCRT) has reshaped the therapeutic landscape, but response prediction remains challenging. This study investigates the interaction between pre-CCRT carcinoembryonic antigen (CEA) and post-CCRT hemoglobin (Hb) levels in predicting the response of locally advanced rectal cancer (LARC) to CCRT. Retrospective data from 93 rectal cancer patients receiving neoadjuvant CCRT were analyzed. Univariate analyses assessed clinical factors associated with tumor regression grade (TRG) and T-stage outcomes. Machine learning identified predictive biomarkers. Interaction effects between CEA and Hb were explored through subgroup analyses. Post-CCRT Hb varied between pre-CCRT CEA groups. The interaction between pre-CCRT CEA and post-CCRT Hb influenced TRG. Males with normal pre-CCRT CEA and anemia showed better treatment responses. Females with elevated pre-CCRT CEA and post-CCRT anemia exhibited poorer responses. The interaction effect between them was significant, indicating that their relationship with TRG was not additive. Inflammatory biomarkers, WBC, neutrophil count, and post-CCRT platelet level correlated with CCRT response. Contrasting with previous findings, anemia was a predictor of better treatment response in males with normal pre-CCRT CEA. The interaction between pre-CCRT CEA and post-CCRT Hb levels predicts the response of LARC to CCRT. CEA, Hb, and sex should be considered when assessing treatment response. Inflammatory biomarkers contribute to response prediction. Understanding these complex relationships can enhance personalized treatment approaches in rectal cancer patients.
Keywords: CCRT; CEA; Hb; LARC; TRG; interaction; predictive biomarkers; treatment response.