The Immune-Inflammatory Status of Breast Cancer Patients as a Prognostic Factor for the Development of Acute Radiation-Induced Skin Injury During Adjuvant Radiotherapy

Abstract

Introduction. Adjuvant radiotherapy (RT) is a standard component of treatment for breast cancer (BC). However, acute radiation dermatitis (ARD) remains a frequent complication that impairs treatment tolerance and quality of life. Identification of predictive markers of individual normal tissue radiosensitivity is a major challenge in modern radiation oncology. Increasing attention is focused on baseline immune-inflammatory status prior to RT and the impact of prior chemotherapy (CT), which may alter systemic inflammation and T-cell homeostasis.

Aim. To evaluate the prognostic significance of integrated inflammatory indices (Systemic Inflammatory Response Index, SIRI; Systemic Immune-Inflammation Index, SII; Aggregate Index of Systemic Inflammation, AISI) and T-cell immunity parameters, including the immune regulatory index (IRI; CD4+/CD8+ ratio), in the development of ARD in BC patients undergoing adjuvant RT, including those who received CT.

Materials and Methods. This prospective study included 168 patients with stage I–III BC who received hypofractionated adjuvant RT. Prior to RT initiation, peripheral blood counts were obtained to calculate SIRI, SII, and AISI. T-lymphocyte subpopulations (CD4+, CD8+) were quantified using flow cytometry. RD were assessed clinically. Patients were stratified based on prior CT exposure.

Results. ARD was observed in all patients, with grade II–III reactions occurring in 32.7 % of cases. Baseline hematological and immunological parameters in the overall cohort were within normal reference ranges. The incidence of grade II–III ARD did not differ significantly between patients with and without prior CT (33.3 vs. 35.4 %, p = 0.48). Patients who received CT demonstrated a more pronounced neutrophil-monocyte profile and relative lymphopenia. Within the CT subgroup, patients who developed grade II–III ARD had significantly higher baseline SIRI values compared to those with grade I reactions (median [IQR]: 1.395 [1.024; 1.767] vs. 1.069 [0.9199; 1.218], p = 0.048). Threshold values of SIRI ≥ 1.25 and SII ≥ 540 were associated with a more than threefold increased risk of developing severe ARD. A reduction in the immune regulatory index, driven by a relative predominance of CD8+ cells, was also observed following CT.

Conclusion. Baseline immune-inflammatory profile and T-cell subset composition influence individual skin radiosensitivity in BC patients undergoing RT. Assessment of these parameters may be useful for personalizing adjuvant RT strategies.