Radiation induced lymphopenia during PRRT: Incidence, course, predictive factors, and association with overall survival.

Abstract

INTRODUCTION: Radiation induced lymphopenia (RIL) is a predictive factor for overall survival in external beam radiotherapy (EBRT). Since both peptide receptor radionuclide therapy (PRRT) and EBRT utilize radiation for treatment effect, RIL could also be a factor in PRRT. AIM: The aim of this study was (1) to determine the incidence of radiation induced lymphopenia during PRRT (2) identify factors that predict lymphopenia during PRRT, and (3) determine the association of lymphopenia during PRRT on overall survival. METHODS: All patients undergoing PRRT between 2015 and 2023 were included in this retrospective study. PRRT consisted of four cycles of 7.4 GBq of [177Lu]Lu-HA-DOTATATE. Hematological assessment was performed at baseline and both three and six weeks after every cycle of PRRT. Uptake of [177Lu]Lu-HA-DOTATATE was measured on the post-therapy SPECT/CT after 24 h after the first cycle of therapy. Binary logistic regression was used to identify factor predicting lymphopenia and cox regression was used to determine the association between severe grade 3–4 lymphopenia and overall survival. RESULTS: A total of 211 patients were included in the study, of which 45.5% developed grade 1–2 lymphopenia and 45.4% developed grade 3–4 lymphopenia. Overall survival was 56 months [95%CI 39–73 months] for patients with grade 0–2 lymphopenia compared to 39 months [95%CI 33–45 months] in the group with grade 3–4 lymphopenia (p = 0.016). Grade 3–4 lymphopenia was a risk factor for worse overall survival compared to grade 0–2 lymphopenia (HR1.68, 95%CI 1.09–2.58, p = 0.018). The total number of cycles of PRRT and baseline lymphocytes counts were risk factors for the development of grade 3–4 lymphopenia (p < 0.001). CONCLUSION: Radiation induced lymphopenia occurs in the majority of patients during PRRT, with 47% developing severe grade 3–4 lymphopenia. The development of severe RIL is associated with worse overall survival and can be partially predicted by baseline lymphocyte levels and the number of cycles of PRRT. Further research is needed in the relationship between lymphocyte radiation dose and lymphopenia and possible strategies to prevent severe lymphopenia from occurring.