3654 - Impact of Radiotherapy on Lymphocyte Subpopulations and Their Prognostic Value in Lung Cancer Patients
Presenter(s)
J. Wang1, D. Liu2, K. Weng3, Q. Lei1, Y. Long1, W. Zhou4, and Y. Wu1; 1Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, China, 2Radiation Oncology Centre, Chongqing University Cancer Hospital, Chongqing, China, 3Department of Radiation Oncology, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Cancer Hospital, Chongqing, China, 4Radiation Oncology Center, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, China
Purpose/Objective(s): Radiotherapy (RT) is a cornerstone of lung cancer treatment, yet its systemic impact on host immune function remains incompletely characterized. This study aims to quantify changes in specific lymphocyte subpopulations following thoracic RT and to evaluate the prognostic significance of baseline and post-treatment immune markers for progression-free survival (PFS) and overall survival (OS).
Materials/Methods: We retrospectively analyzed 325 lung cancer patients treated with definitive or palliative RT between 2012 and 2022. Peripheral blood lymphocyte subsets, including CD4+, CD8+, total T cells, B cells, and NK cells, along with derived ratios, were assessed via flow cytometry at baseline and post-RT (median 30 days after completion). Clinical characteristics, treatment parameters, and survival outcomes were extracted from electronic medical records. Survival analysis was performed using the Kaplan-Meier method with log-rank tests. Paired t-tests were utilized to compare pre- and post-RT lymphocyte values.
Results:
The median age of the cohort was 63 years (range: 35–85 years). Histological subtypes included squamous cell carcinoma (39.7%), adenocarcinoma (38.5%), and others (21.8%). Disease stage distribution comprised Stage III (50.8%) and Stage IV (39.4%). The median RT dose was 59 Gy (range: 8–77 Gy) delivered in 30 fractions. Post-RT analysis revealed significant reductions in all measured lymphocyte subpopulations (all p < 0.001). Specifically, total lymphocyte counts decreased by 33.9%, dropping from a median of 1,369 cells/µL at baseline to 905 cells/µL post-treatment. CD4+ T cells exhibited the most pronounced decline of 46.6% (from 545 to 291 cells/µL), followed by B cells which decreased by 50.6% (from 130 to 64 cells/µL). CD8+ T cells and NK cells decreased by 16.5% (from 380 to 317 cells/µL) and 25.6% (from 252 to 188 cells/µL), respectively. Regarding relative proportions, the percentage of CD4+ cells significantly decreased from 40.3% to 33.2% (p < 0.001), whereas the percentage of CD8+ cells increased from 27.6% to 34.1% (p < 0.001). Consequently, the median CD4/CD8 ratio inverted, declining from 1.51 at baseline to 0.98 post-RT. With a median follow-up of 791 days, the median PFS was 510 days (event rate: 85.8%), and the median OS was 791 days (event rate: 60.6%).Conclusion: Thoracic radiotherapy induces profound systemic immunosuppression, characterized by a preferential depletion of CD4+ T cells and B cells, leading to an inversion of the CD4/CD8 ratio. Baseline immune status, particularly the CD4/CD8 ratio, serves as an independent prognostic factor for PFS in lung cancer patients. These findings suggest that pre-treatment immune profiling may aid in risk stratification. Future prospective trials should investigate strategies to mitigate RT-induced lymphopenia and preserve immune function.