How Does Lymphocyte Depletion Affect Rectal Cancer Radiotherapy Outcomes?

Background Pelvic radiotherapy for rectal cancer inevitably exposes substantial volumes of hematopoietic bone marrow, which are highly susceptible to radiation-induced damage. This leads to lymphopenia, with implications for both immune function and tumor control. The impact of lymphocyte depletion during treatment, particularly its correlation with pathological response, local control, and overall survival, remains an area of active research. Methods In this study, we analyzed lymphocyte variations during radiotherapy for rectal cancer and their relationship to treatment outcomes. Delta lymphocyte count was used as a marker for radiation-induced lymphopenia (RIL), defined as the difference between the highest and lowest lymphocyte levels during treatment. A cohort of rectal cancer patients receiving pelvic radiotherapy was followed to assess the relationship between radiation-induced lymphopenia and progression-free survival, pathological response, and treatment-related toxicity, including mucositis, dermatitis, and xerostomia. Results A total of 97 patients were included, with a median age of 69 years. Tumors were mostly located less than 5 cm from the anal margin (53.4%). The majority had T3-T4 disease (59.7%), and 80.4% had clinically positive lymph nodes. Treatment included external radiotherapy (mean dose 50.2 Gy) and chemotherapy, with 92.8% receiving 3D radiotherapy. The median follow-up was 72 months. The incidence of grade 3-4 lymphopenia was 25.21%, with a mean delta lymphopenia (ΔL) of 350.6 cells. The Tumor Regression Grade (TRG) score showed 61.2% had a response of >1. Higher radiation doses (>25 Gy) were associated with greater reductions in lymphocyte counts (Spearman correlation = 0.45, p=0.03). Kaplan-Meier analysis revealed better progression-free survival for patients with ΔL ≤300 cells (HR=0.65, p=0.0013). Multivariate analysis confirmed that ΔL was a significant predictor of progression-free survival (HR=0.68, p=0.012), with larger ΔL values linked to poorer survival. Conclusion Delta lymphocyte count serves as a reliable biomarker for radiation-induced immune suppression and is predictive of pathological response and survival outcomes in rectal cancer patients undergoing pelvic radiotherapy. Our findings underscore the importance of considering immune preservation in radiotherapy planning. Tailored interventions, such as marrow-sparing techniques and immunomodulatory strategies, could potentially improve treatment efficacy and reduce toxicities.