Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases After Initial Peptide Receptor Radionuclide Therapy.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) and radioembolization are increasingly used in neuroendocrine neoplasms patients. However, concerns have been raised on cumulative hepatotoxicity. The aim of this sub-analysis was to investigate hepatotoxicity of yttrium-90 resin microspheres radioembolization in patients who were previously treated with PRRT. METHODS: Patients treated with radioembolization after systemic radionuclide treatment were retrospectively analysed. Imaging response according to response evaluation criteria in solid tumours (RECIST) v1.1 and clinical response after 3 months were collected. Clinical, biochemical and haematological toxicities according to common terminology criteria for adverse events (CTCAE) v4.03 were also collected. Specifics on prior PRRT, subsequent radioembolization treatments, treatments after radioembolization and overall survival (OS) were collected. RESULTS: Forty-four patients were included, who underwent a total of 58 radioembolization procedures, of which 55% whole liver treatments, at a median of 353 days after prior PRRT. According to RECIST 1.1, an objective response rate of 16% and disease control rate of 91% were found after 3 months. Clinical response was seen in 65% (15/23) of symptomatic patients after 3 months. Within 3 months, clinical toxicities occurred in 26%. Biochemical and haematological toxicities CTCAE grade 3-4 occurred in ≤ 10%, apart from lymphocytopenia (42%). Radioembolization-related complications occurred in 5% and fatal radioembolization-induced liver disease in 2% (one patient). A median OS of 3.5 years [95% confidence interval 1.8-5.1 years] after radioembolization for the entire study population was found. CONCLUSION: Radioembolization after systemic radionuclide treatments is safe, and the occurrence of radioembolization-induced liver disease is rare. LEVEL OF EVIDENCE: 4, case series.

Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases: International Multicenter Study on Efficacy and Toxicity.

PURPOSE: Radioembolization of liver metastases of neuroendocrine neoplasms (NEN) has shown promising results; however, the current literature is of limited quality. A large international, multicentre retrospective study was designed to address several shortcomings of the current literature. MATERIALS: 244 NEN patients with different NEN grades were included. METHODS: Primary outcome parameters were radiologic response 3 and 6 months after treatment according to RECIST 1.1 and mRECIST. Secondary outcome parameters included clinical response, clinical and biochemical toxicities. RESULTS: Radioembolization resulted in CR in 2%, PR in 14%, SD in 75% and PD 9% according to RECIST 1.1 and in CR in 8%, PR in 35%, SD in 48% and PD in 9% according to mRECIST. Objective response rates improved over time in 20% and 26% according to RECIST 1.1. and mRECIST, respectively. Most common new grade 3-4 biochemical toxicity was lymphocytopenia (6.7%). No unexpected clinical toxicities occurred. Radioembolization-specific complications occurred in < 4%. In symptomatic patients, improvement and resolution of symptoms occurred in 44% and 34%, respectively. Median overall survival from first radioembolization was 3.7, 2.7 and 0.7 years for G1, G2 and G3, respectively. Objective response is independent of NEN grade or primary tumour origin. Significant prognostic factors for survival were NEN grade/Ki67 index, ≥ 75% intrahepatic tumour load, the presence of extrahepatic disease and disease control rate according to RECIST 1.1. CONCLUSION: Safety and efficacy of radioembolization in NEN patients was confirmed with a high disease control rate of 91% in progressive patients and alleviation of NEN-related symptoms in 79% of symptomatic patients. LEVEL OF EVIDENCE: 4.

Hypoxia-inducible factor-1α regulation of myeloid cells.

Hematopoietic myeloblasts give rise to macrophages, dendritic cells, and neutrophils. Circulating myeloid cells detect invading microbes using pattern recognition receptors and subsequently orchestrate an innate immune response to contain and kill the pathogens. This innate immune response establishes an inflammatory niche characterized by hypoxia due to host and pathogen factors. Hypoxia-inducible factor (HIF) transcription factors are the primary regulators of the myeloid response to hypoxia. In particular, HIF-1α is a critical hub that integrates hypoxic and immunogenic signals during infection or inflammation. Hypoxia induces HIF-1α stabilization, which drives metabolic and phenotypic reprogramming of myeloid cells to maximize antimicrobial potential. HIF-1α activity in myeloid-derived cells enhances the host response to infection, but may also play a role in pathogenic inflammatory processes, such as atherosclerosis. In this review, we summarize recent advances that have elucidated the mechanism by which myeloid cells regulate HIF-1α activity and, in turn, how HIF-1α shapes myeloid cell function.