Study Protocol: Adjuvant Holmium-166 Radioembolization After Radiofrequency Ablation in Early-Stage Hepatocellular Carcinoma Patients—A Dose-Finding Study (HORA EST HCC Trial)

Dutch Hepatocellular Cholangiocarcinoma Group

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Purpose: To investigate the biodistribution of holmium-166 microspheres (166Ho-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to establish a perfused liver administration dose that results in a tumoricidal dose of holmium-166 on the hyperaemic zone around the ablation necrosis (i.e. target volume). Materials and Methods: This is a multicentre, prospective, dose-escalation study in HCC patients with a solitary lesion 2–5 cm, or a maximum of 3 lesions of ≤ 3 cm each. The day after RFA patients undergo angiography and cone-beam CT (CBCT) with (super)selective infusion of technetium-99 m labelled microalbumin aggregates (99mTc-MAA). The perfused liver volume is segmented from the CBCT and 166Ho-MS is administered to this treatment volume 5–10 days later. The dose of holmium-166 is escalated in a maximum of 3 patient cohorts (60 Gy, 90 Gy and 120 Gy) until the endpoint is reached. SPECT/CT is used to determine the biodistribution of holmium-166. The endpoint is met when a dose of ≥ 120 Gy has been reached on the target volume in 9/10 patients of a cohort. Secondary endpoints include toxicity, local recurrence, disease-free and overall survival. Discussion: This study aims to find the optimal administration dose of adjuvant radioembolization with 166Ho-MS after RFA. Ultimately, the goal is to bring the efficacy of thermal ablation up to par with surgical resection for early-stage HCC patients. Trial registration: identifier: NCT03437382.
Original languageEnglish
Pages (from-to)1057-1063
Number of pages7
JournalCardiovascular and interventional radiology
Issue number8
Early online date26 May 2022
Publication statusPublished - Aug 2022


  • Early-stage HCC
  • Hepatocellular carcinoma
  • Holmium-166
  • Radioembolization
  • Radiofrequency ablation
  • TARE
  • Thermal ablation

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