Abstract
PurposeIn 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).MethodsAll 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.ResultsThirty-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.ConclusionsToxicity 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.
Highlights
Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE is standard of care in patients with somatostatin receptor (SSTR) positive grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (NET)
Patients were eligible for inclusion in de HEPAR PLuS study if they were ≥ 18 years old; had Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2; had at least three measurable liver metastases according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1); had treatment with [166Ho]-radioembolization within 20 weeks after the final cycle of PRRT
After sequential PRRT and [166Ho]-radioembolization, additional short-term lymphopenia was observed in 55% of the treated patients with well-differentiated NET, 32% had grade 3–4 lymphopenia
Summary
Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE is standard of care in patients with somatostatin receptor (SSTR) positive grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (NET). It is indicated following progression after initial treatment with somatostatin analogs (SSA). Within a 6-month follow-up period, grade 3 lymphopenia was observed in 23% of patients This is a phenomenon that is known to occur after both PRRT and radioembolization, and is thought to be caused by the immune response initiated after radiation therapy of the tumors, direct irradiation of white blood cells, and targeting of B-lymphocytes by overexpression of SST2-receptors [4, 5]. The NLR and TLR were proposed as prognostic factors after radioembolization [10]
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