Radiation-induced lymphopenia: A data compilation to unveil relevant factors and mitigation strategies.

Purpose: Radiation-induced lymphopenia (RIL) is a common complication of radiation therapy (RT) that can undermine antitumor immunity and diminish the efficacy of immunotherapy. While RIL is a known predictor of poor outcomes, its underlying mechanisms and key determinants remain poorly characterized. Materials and Methods: We systematically compiled and quantitatively analyzed published data on absolute lymphocyte count (ALC) dynamics during and after RT. A total of 142 ALC curves from 52 publications were digitized and integrated into a standardized database. This database encompasses various RT modalities, including therapy with X-rays or charged particles, as well as extracorporeal irradiation of blood (ECIB). Results: Analysis revealed consistent lymphocyte depletion during treatment. By the end of RT, median ALCs declined to 24% (range: 1.5-78%) of baseline for intracorporeal exposure and 10% (range: 1-60%) for ECIB. Recovery was incomplete and cancer-type-dependent, reaching only a median of 55% (range: 33-90%) of baseline within one year. We identified baseline ALC, planning target volume (PTV), and dosimetric parameters as key predictors of severe lymphopenia. A low rate of lymphocyte depletion during treatment was frequently associated with impaired long-term recovery. Particle therapy was associated with an average 11% higher end-of-treatment ALC compared to photon therapy, underscoring the lymphocyte-sparing benefit of reduced integral dose. Conclusions: This work establishes a comprehensive, quantitative foundation for understanding RIL. The developed ALC database supports mechanistic investigation and enables model-based approaches to predict lymphocyte dynamics, guiding the design of lymphocyte-sparing treatment strategies, including particle therapy.