Radiation-induced lymphopenia: the main aspects to consider in immunotherapy trials for endometrial and cervical cancer patients

Background Although the chemotherapy-induced depletion of circulating white blood cells (WBC) is well recognized, the impact of exclusive radiotherapy (RT) on the different subpopulations of WBC remains unexplored. This may be important for immunotherapy administrated in combination with radiation, especially in malignant tumors usually treated with RT or chemoradiotherapy (CRT), and characterized by a high mutational burden, such as endometrial (EC) or cervical cancer (CC). We aimed to evaluate the impact of RT and CRT on circulating WBC in uterine cancers and its correlation with survival. Material and methods A total of 202 consecutive patients with uterine cancers treated with RT or CRT between 2009 and 2016 in a large European center and with available basal and post-treatment blood tests were retrospectively evaluated. EC and CC patients were analyzed separately. The differences between pre- and post- treatment WBC mean values were evaluated independently in patients treated with CRT and exclusive RT. Two-sided T test for paired samples and Kaplan-Meier curves were applied for analysis (p value < 0.05, SPSS v.23). Results Among EC patients, 29 received CRT and 34 exclusive postoperative RT, while in CC cohort, 105 were treated with CRT and 34 with RT. In both cohorts, CRT affected significantly all WBC subtypes, whereas exclusive RT decreased only lymphocytes population (p = 0.000). Radiation-induced lymphopenia (RIL) had no impact on survival outcomes. Conclusions The selective depletion of lymphocytes after RT was significant in both EC and CC. Our results are of interest for further research on RIL and for design of immunotherapy-based clinical trials.