Comprehensive Analysis of Lymphocyte Loss Kinetics in Patients Treated with Focal Fractionated Radiation Therapy

e14191 Background: Radiation (RT)-induced lymphopenia (RIL) is associated with worse survival in patients with solid tumors as well as lower response rates to checkpoint inhibitors. This analysis aimed to model the kinetics of lymphocyte depletion during RT to assist in predicting RIL risk. Methods: This registry-based study included 419 patients who received either total body irradiation (TBI; n = 30), stereotactic body RT (SBRT; n = 73), or conventional chemoradiation (CRT; n = 316). For each patient, serial absolute lymphocyte counts (ALCs) were plotted against RT fraction number. The initial 3 weeks of treatment for conventionally irradiated patients and the entirety of treatment for SBRT and TBI patients were fit to exponential decay in the form ALC(x) = ae-bx. From those fits, percent per fraction loss in ALC (PFLAC) was calculated as PFLAC = (1 – e-b)*100, and multivariable regression was performed to find its significant predictors. Results: Curves were well fitted by exponential decay for all RT techniques (median linearized R2 0.98, 0.93, and 0.97 for patients treated with TBI, SBRT, and CRT, respectively). In CRT patients, apparent ALC loss rate slowed after week 3, potentially due to lymphocyte repopulation or other factors. TBI and SBRT patients completed RT before the end of the exponential decay phase, and their ALC loss rates remained unchanged throughout RT. Initial PFLAC varied significantly with treatment technique. Mean PFLAC was 35.5%, 24.3%, and 10.77% for patients treated with TBI, SBRT, and CRT, respectively (p < 0.001). Significant predictors of PFLAC varied by site and included field size, dose per fraction, mean spleen dose, chemotherapy backbone, and age. In pancreas cancer patients, gemcitabine was associated with a higher PFLAC (mean = 10.7) than 5-FU (mean = 8.3) after adjustment for covariates (p < 0.001). Finally, total % ALC loss during RT was highly correlated with PFLAC (p < 0.001). Conclusions: Lymphocyte depletion kinetics during the initial phase of fractionated RT are characterized by pure exponential decay. Initial PFLAC is strongly correlated with RT planning parameters and predicts total % ALC loss. The highest ALC loss rates were associated with RT-only regimens, implying that concurrent chemotherapy is not solely responsible for lymphopenia in patients receiving CRT. This work may also assist in selecting patients for adaptive RT approaches to mitigate RIL risk.