Prognostic Value of Lymphocyte Subset Levels in Hepatocellular Carcinoma Following Conventionally Fractionated vs. Stereotactic Body Radiotherapy

Background and aim: Radiotherapy (RT)-induced lymphopenia is associated with poor prognosis. This study aimed to compare the effects of conventionally fractionated radiotherapy (CFRT) and stereotactic body radiotherapy (SBRT) on lymphocyte subpopulations in hepatocellular carcinoma (HCC) patients and to evaluate the prognostic value of lymphocyte subset levels. Materials and Methods A retrospective analysis was conducted on 137 HCC patients who underwent CFRT or SBRT between July 2011 and January 2018. Variables were obtained within 1 week before RT, and at 1 day and 2 months post-RT, respectively. Univariate and multivariate Cox regression analyses were conducted to investigate independent prognostic factors for overall survival (OS). Results The one-year and two-year OS rates were 80.0% and 55.0%, respectively. Multivariate analysis identified tumor size > 4.5cm, multiple tumors, and post-RT CD4 + T cell count < 231/µL and CD8 + T cell count < 179/µL as independent factors associated with inferior OS in HCC patients. Severe RT-induced lymphopenia (< 0.5*10^ ⁹ /L) occurred in 70.0% of patients following CFRT compared to 23.0% in SBRT patients. Patients receiving SBRT exhibited higher total lymophocyte counts and subset levels at 1 day and 2 months post-treatment compared to those receiving CFRT (P < 0.05). Further analysis revealed that CD19 + B cells were predominantly depleted and recovered more slowly than other populations while CD8 + T cells demonstrated rapid recovery. In the SBRT group, patients with OS > 2 years exhibited higher levels of CD4 + T cell and CD8 + T cell counts compared to those with OS < 2 years (P < 0.05). Conclusion SBRT induced less severe lymphopenia than CFRT. Peripheral lymphopenia of CD4 + and CD8 + T cells post-SBRT may independently predict survival for HCC patients.