Radiation Induced Lymphopenia is Associated with the Effective Dose to the Circulating Immune Cells (EDIC) for Breast Cancer

Abstract

Radiation induced lymphopenia (RIL) has been reported to associate with treatment outcome in many types of solid cancers, including breast cancer of small series. In this study, we hypothesized that effective dose to circulating immune cells (EDIC) impacts the severity of radiation-induced lymphopenia in breast cancer. Breast cancer patients who received adjuvant radiation were enrolled in this study. Radiation dosimetric factors such as RT fields, RT fractionation schema, use of electron, mean cardiac dose, mean ipsilateral/bilateral lung dose, integral dose of the total body was collected retrospectively. A previously published EDIC model, which considered that the exposure of circulating immune cells as the proportion of blood flow into blood containing organs including lung, heart, and the volume of the exposed area of the total body, were used for this study. The model is expressed as EDIC = 0.12*MLD+0.08*MHD+0.45+0.35*0.85*n451/2*ITD61.8*103, where MLD, MHD, and ITD is the mean lung dose, mean heart dose and integral dose, n is the number of radiation fractions. The post- and pre-radiation lymphocyte ratio was calculated as the end point to predict lymphopenia. Linear regression between the lymphocyte ratio and EDIC was used for the analysis. The lymphocyte ratios were also compared by dividing patients into 3 EDIC groups. T-test was used for the comparison. Between March 2015 to February 2020, a total of 1288 breast cancers patients received radiation in clinical oncology of Hong Kong University Shenzhen Hospital and 735 patients with complete CBC results were included in this study. The lymphocyte ratio decreased linearly with increasing EDIC (R2 = 0.23, p<0.0001). The median lymphocyte ratio was 73.1%, 62.2% and 36.4% respectively, when EDIC was ≤ 0.75Gy, >0.75Gy but ≤1.25Gy, and >1.25Gy. The average EDIC was 75%±21%, 64%±19%, and 41%±23% correspondingly for the 3 EDIC groups (p<0.0001). EDIC is significantly associated with lymphocyte count changes and NCI defined lymphopenia after radiation. EDIC may be used to predict radiation induced lymphopenia and guide radiation plan optimization for breast cancer patients treated with radiotherapy.