Effects Of Different Radiotherapy Techniques On Peripheral Lymphocyte Subsets In Patients With Hepatocellular Carcinoma

To investigate the prognostic value of radiotherapy (RT) induced lymphopenia for patients with hepatocellular carcinoma (HCC), and to compare the influences of stereotactic body radiation therapy (SBRT), conventionally fractionated RT (CFRT) and hyper-fractionated RT (HFRT) on the levels of total peripheral lymphocyte counts (TPLCs) and lymphocyte sub-populations. The ethics committee approved this study, and informed consents were obtained. A total of 128 HCC patients treated with RT between July 2011 and January 2018 were retrospectively analyzed. Variables were obtained within 1 week before RT, 2 months and 5 months after RT, respectively. The effects of different RT techniques on lymphocyte subsets including CD3+, CD4+, CD8+ T cells, CD19+ B cells, and CD16+56+ NK cells among HCC patients were compared using repeated measures analysis of variance. Univariate and multivariate Cox regression analyses were used to explore the independent prognostic factors for patients’ overall survival (OS). The one-, two- and three-year OS rates were 93.9%, 76.9%, and 62.4%, respectively. Multivariate analysis results revealed that variables including tumor size>3.5cm, tumor necrosis factor-alpha level<5.6 ng/ml and post-treatment TPLC<0.57×109/L were independent factors for inferior OS. The mean TPLCs before RT, 2 months and 5 months after RT were 1.3×109/L, 0.7×109/L and 1.1×109/L, respectively. There showed no significant differences of baseline lymphocyte subset counts among different RT techniques. However, the levels of TPLCs and various lymphocyte sub-populations for patients receiving SBRT were higher than those treated with CFRT and HFRT both at 2 months and 5 months after therapy (P<0.05 for all). Among all the lymphocyte subsets, CD19+ B cells were mostly depleted and recovered much slower than other populations, and this phenomenon was more obvious in CFRT and HFRT (pre- and post-treatment values were 171.7 cells/μl and 93.3 cells/μl, 173.2 cells/μl and 9.0 cells/μl, 165.3 cells/μl and 16.2 cells/μl for SBRT, CFRT and HFRT, respectively). Further analysis demonstrated that there were significant differences in TPLCs and CD8+ T cell counts in patients with OS>2 years versus OS<2 years for SBRT and HFRT (P<0.05 for all). Peripheral lymphopenia after RT might be an independent prognostic factor for worse OS in HCC patients. SBRT lead to less severe lymphocyte depletion than CFRT and HFRT, especially for CD19+ B cells.