In Patients Treated by Selective Internal Radiotherapy, Cellular In Vitro Immune Function Is Predictive of Survival

SIMPLE SUMMARY: To treat malignant liver tumors, the liver can be irradiated locally with the injection of radioactive microparticles, by a therapy called selective internal radiotherapy. We could previously show that this treatment is correlated with an impaired immune function of white blood cells. As the liver is a well-perfused organ, we assume that during their passage through the liver, white blood cells become irradiated, which leads to this functional impairment. In the current study, we observed in 25 patients treated with selective internal radiotherapy that a higher degree of immunosuppression was predictive of a 2-to-3.5-times shorter survival. We assessed the immune function radioactively by a cell proliferation assay, after stimulation with four microbial antigens. ABSTRACT: In patients with liver malignancies, the cellular immune function was impaired in vitro after selective internal radiotherapy (SIRT). Because immunosuppression varied substantially, in the current study, we investigated in 25 SIRT patients followed up for ten years whether the lymphocyte function was correlated with survival. Peripheral blood mononuclear cells were stimulated with four microbial antigens (tuberculin, tetanus toxoid, Candida albicans and CMV) before therapy and at four time points thereafter, and lymphocyte proliferation was determined by H3-thymidine uptake. The median sum of the responses to these four antigens decreased from 39,464 counts per minute (CPM) increment (range 1080–204,512) before therapy to a minimum of 700 CPM increment on day 7 after therapy (0–93,187, p < 0.0001). At all five time points, the median survival in patients with weaker responses was 2- to 3.5-fold shorter (p < 0.05). On day 7, the median survival in patients with responses below and above the cutoff of a 2 CPM increment was 185 and 523 days, respectively (χ(2) = 9.4, p = 0.002). In conclusion, lymphocyte function could be a new predictor of treatment outcome after SIRT.