Prognostic value of lymphocyte subset levels in hepatocellular carcinoma following conventionally fractionated vs. stereotactic body radiotherapy

Abstract

Aim: The aim of this study was to compare the effects of conventionally fractionated radiotherapy (CFRT) and stereotactic body radiotherapy (SBRT) on peripheral lymphocyte subset levels in patients with hepatocellular carcinoma (HCC), and to assess the association between radiotherapy (RT)-induced lymphopenia and patient prognosis.

Methods: A retrospective analysis was conducted on 137 HCC patients who underwent either CFRT or SBRT between July 2011 and January 2018. Variables were obtained within 1 week before RT, and 1 day and 2 months post-RT, respectively. Peripheral lymphocyte subsets, including CD4+, CD8+, CD19+, and NK cells, were measured using flow cytometry. 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 > 4.5 cm, 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 lymphopenia (< 0.5 × 10⁹/L) occurred in 70.0% of patients following CFRT compared to 23.0% in SBRT patients. Patients who received SBRT exhibited higher total lymphocyte counts and subset levels 1 day and 2 months post-treatment compared to those receiving CFRT (P < 0.05). Logistic regression analysis identified the number of RT fractions as an independent factor for severe lymphopenia. Further analysis revealed that CD19+ B cells were predominantly depleted and recovered more slowly than other populations, whereas CD8+ T cells demonstrated rapid recovery. Among SBRT patients, higher levels of CD4+ and CD8+ T cells post-treatment were associated with longer OS (P < 0.05).

Conclusion: SBRT may induce less severe lymphopenia than CFRT. Decreases in CD4+ and CD8+ T cell levels post-SBRT may independently predict worse OS in HCC patients.

Keywords

Radiotherapy / hepatocellular carcinoma / lymphopenia / overall survival

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