Dynamic Lymphocyte Changes Following Transarterial Radioembolization: Association with Normal Liver Dose and Effect on Overall Survival

Abstract

Objective To evaluate the dynamic changes of lymphocytes following transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) and their relationship to normal liver dose (NLD). Materials and Methods A total of 93 patients who underwent 102 treatments were retrospectively reviewed. Absolute lymphocyte counts pretreatment and at 1, 3, 6, and 12 months were evaluated. Kaplan–Meier, Spearman correlation, receiver operating characteristic (ROC) curve, and area under the curve (AUC) analyses were performed. Results The mean absolute lymphocyte count at baseline was 1.25 ± 0.79 10 3 /µL which was significantly greater than 1 (0.71 ± 0.47 10 3 /µL, p <0.0001), 3 (0.79 ± 0.77 10 3 /µL, p =0.0003), and 6 (0.81 ± 0.44 10 3 /µL, p =0.0001) months, but not significantly different than 12 (0.92 ± 0.8 10 3 /µL, p =0.12) months post treatment. There was a modest negative correlation between NLD and lymphocyte count at 1 month (rho= −0.216, p =0.03), which strengthened at 3 months post treatment (rho= −0.342, p =0.008). AUC of ROC analysis between absolute lymphocyte count ≤1 10 3 /µL or >1 10 3 /µL at 1, 3, 6, and 12 months post treatment was 0.625, 0.676, 0.560, and 0.794, respectively. Univariate analysis of overall survival when separating patients by a lymphocyte count of ≤1 10 3 /µL and >1 10 3 /µL demonstrated a significant difference at 1 (HR: 0.56, 95% CI: 0.33–0.95, p =0.03), 3 (HR: 0.41, 95% CI: 0.18–0.94, p =0.035) and 6 (HR: 0.36, 95% CI: 0.17–0.77, p =0.008) months post treatment, but not pretreatment or at 12 months. Conclusion NLD may correlate with lymphocyte depression at 1 and 3 months and lymphopenia may portend a worse overall survival in the post treatment setting.

The immune response of hepatocellular carcinoma after locoregional and systemic therapies: The available combination option for immunotherapy

“…Clinical studies have suggested that higher doses of radiation to the tumor increase the likelihood of inducing a positive immune response (35). A retrospective assessment of the dynamic changes in lymphocytes following TARE of HCC and its association with normal liver dose (NLD) of TARE found a moderate negative association between the NLD and lymphocyte count at 1 month posttreatment that was most significant at 3 months posttreatment (36). In an early prospective clinical study, after TARE, proinflammatory (IL-6 and IL-8) and oxidative stress (malondialdehyde) markers continued to increase, endothelial damage markers (vW factor and PAI-1) and coagulation cascades (factor VIII, PAI-1, and D-dimer) were induced, and a significant increase in factors associated with liver regeneration (FGF-19 and HGF) was observed (36).…”

Liver-Directed Therapy Combined with Systemic Therapy: Current Status and Future Directions

“…To further complicate things, the liver is a complex immune environment, with many lymphocytes present. 92 Therefore, dose to normal liver may affect the ability to prime the immune system, with early data seeming to signal that it may at least correlate with posttreatment lymphocyte counts. 92 However, very little data are available to know what affect this has on specific clonal populations.…”

“…92 Therefore, dose to normal liver may affect the ability to prime the immune system, with early data seeming to signal that it may at least correlate with posttreatment lymphocyte counts. 92 However, very little data are available to know what affect this has on specific clonal populations. These important questions must be further evaluated, and answers should at least attempt to be gathered.…”