Inflammatory markers and long term hematotoxicity of holmium-166-radioembolization in liver-dominant metastatic neuroendocrine tumors after initial peptide receptor radionuclide therapy

Abstract

Purpose: In patients with neuroendocrine tumor liver metastases, additional tumor reduction can be achieved by sequential treatment with [166Ho]-radioembolization after peptide receptor radionuclide therapy (PRRT). The aim of this study was to analyze hematotoxicity profiles, (i.e. lymphocyte and neutrophile toxicity) and the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and thrombocyte-to-lymphocyte ratio (TLR). Methods: All patients included in the prospective HEPAR PLuS study were included in this study. Blood testing was performed at baseline (before radioembolization) and at regular intervals during 1-year follow-up. Radiological response was assessed at 3, 6, 9, and 12 months according to RECIST 1.1. Logistic regression was used to analyze the prognostic value of NLR and TLR on response. Results: Thirty-one patients were included in the toxicity analysis; thirty were included in the response analysis. Three weeks after radioembolization, a significant decrease in lymphocyte count (mean change − 0.26 × 109/L) was observed. Ten patients (32.2%) experienced grade 3–4 lymphocyte toxicity. This normalized at 6 weeks and 3 months after treatment, while after 6 months a significant increase in lymphocyte count was observed. An increase in NLR and TLR at 3 weeks, compared to baseline, significantly predicted response at 3 months (AUC = 0.841 and AUC = 0.839, respectively) and at 6 months (AUC = 0.779 and AUC = 0.765). No significant relation with survival was found. Conclusions: Toxicity after sequential treatment with PRRT and [166Ho]-radioembolization is limited and temporary, while significant additional benefit can be expected. Change in NLR and TLR at 3-weeks follow-up may be valuable early predictors of response. Trial registration ClinicalTrials.gov, NCT02067988. Registered 20 February 2014, https://clinicaltrials.gov/ct2/show/record/NCT02067988.