Ho-166 Radioembolization After Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumor Liver Metastases

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In a single-center Dutch phase II trial reported in The Lancet Oncology, Braat et al found that holmium Ho-166 radioembolization produced responses in patients with neuroendocrine tumor liver metastases who had received peptide receptor radionuclide therapy with lutetium Lu-177 dotatate.

Study Details

In the study, 31 patients enrolled at the University Medical Center Utrecht between October 2014 and September 2018 received holmium Ho-166 radioembolization within 20 weeks after four cycles of lutetium Lu-177 dotatate. Radioembolization was performed during a 3-day hospital admission. The primary endpoint was objective liver tumor response in the treated liver volume according to Response Evaluation Criteria in Solid Tumors, version 1.1, analyzed per protocol at 3 months.


  • Holmium Ho-166 radioembolization produced responses in 43% of patients at 3 months.
  • One patient had fatal radioembolization-induced liver disease.


All 30 evaluable patients completed 6 months of follow-up. Objective response in the treated liver volume was observed in 13 (43%) of 30 patients at 3 months and in 14 (47%) at 6 months. All responses were partial responses; an additional 50% and 37% of patients had stable disease as best response at 3 months and 6 months, respectively.  

Adverse Events

Among the 31 patients who received radioembolization, the most common grade 3 or 4 clinical and laboratory toxicities within 6 months were abdominal pain (10%), increased γ-glutamyl transpeptidase (54%), and lymphocytopenia (23%). One patient had fatal radioembolization-induced liver disease; in addition to this patient, two additional patients had serious adverse events—gastric ulcer and perforated cholecystitis)—which were considered to be unrelated to treatment.

The investigators concluded: “[Holmium Ho-166] radioembolization, as an adjunct to peptide receptor radionuclide therapy in patients with neuroendocrine neoplasm liver metastases, is safe and efficacious. Radioembolization can be considered in patients with bulky liver disease, including after peptide receptor radionuclide therapy. A future randomized, controlled study should investigate the added benefit of this treatment on progression-free survival.”

Arthur J.A.T. Braat, MD, of the Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, is the corresponding author for The Lancet Oncology article.

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