Abstract
<title>Abstract</title> <p>Background: Lung cancer is a global threat. Radiotherapy plus immunotherapy is standard for advanced disease, but radiation‑induced lymphopenia (RIL) may weaken antitumor immunity and compromise survival. This study aimed to characterize the dynamic changes in absolute lymphocyte count from before radiotherapy through peripheral blood lymphocyte recovery in patients with advanced lung cancer, and to evaluate their influence on survival outcomes. Methods A retrospective analysis was conducted on 132 patients with advanced lung cancer who received thoracic radiotherapy combined with immunotherapy between June 2022 and December 2025. Dynamic changes in ALC before, during, and at 1 month after radiotherapy, the time to ALC recovery, and the occurrence of lymphopenia were analyzed. Univariable and multivariable linear regression were used to identify factors influencing nadir ALC and ALC at 1 month after radiotherapy. Cox regression was performed to assess the association of ALC with overall survival and progression-free survival. Results The median age was 65 years, and the median follow-up was 32.0 months. During radiotherapy, the median nadir ALC fell to 575 cells/µL; lymphopenia developed in 81.9% of patients, and severe (grade ≥ 3) lymphopenia occurred in 40.5%. At 1 month after radiotherapy, the ALC partially recovered to 870 cells/µL, with a median recovery time of 64 days; 12% of patients had not recovered by 2 years. Multivariable analysis identified radiotherapy technique and baseline ALC as independent determinants of the nadir ALC, with stereotactic body radiotherapy and a higher baseline ALC being protective factors. The median OS was 18 months. Nadir ALC and time to ALC recovery were independent risk factors for OS. Conclusions Patients with advanced lung cancer receiving thoracic radiotherapy and immunotherapy experience a high incidence of radiation-induced lymphopenia. Nadir ALC and time to ALC recovery are independent adverse prognostic factors for OS. Dynamic ALC monitoring may aid prognostic stratification, and the development of lymphocyte-sparing radiotherapy strategies has the potential to improve survival outcomes.</p>