Adjuvant holmium-166 radioembolization after radiofrequency ablation in early-stage hepatocellular carcinoma patients: a dose-finding study (HORA EST HCC trial)

Pim Hendriks, Daphne D. D. Rietbergen, Arian R. van Erkel, Minneke J. Coenraad, Mark J. Arntz, Roel J. Bennink, Andries E. Braat, Stijn Crobach, Otto M. van Delden, Petra Dibbets-Schneider, Tom van der Hulle, Heinz-Josef Klümpen, Rutger W. van der Meer, J. Frank W. Nijsen, Catharina S. P. van Rijswijk, Joey Roosen, Bastian N. Ruijter, Frits Smit, Mette K. Stam, R. Bart TakkenbergMaarten E. Tushuizen, Floris H. P. van Velden, Lioe-Fee de Geus-Oei, Mark C. Burgmans

Research output: Contribution to journalArticleAcademicpeer-review


Purpose: The aim of this study was to investigate the biodistribution of (super-)selective trans-arterial radioembolization (TARE) with holmium-166 microspheres (166Ho-MS), when administered as adjuvant therapy after RFA of HCC 2–5 cm. The objective was to establish a treatment volume absorbed dose that results in an absorbed dose of ≥ 120 Gy on the hyperemic zone around the ablation necrosis (i.e., target volume). Methods: In this multicenter, prospective dose-escalation study in BCLC early stage HCC patients with lesions 2–5 cm, RFA was followed by (super-)selective infusion of 166Ho-MS on day 5–10 after RFA. Dose distribution within the treatment volume was based on SPECT-CT. Cohorts of up to 10 patients were treated with an incremental dose (60 Gy, 90 Gy, 120 Gy) of 166Ho-MS to the treatment volume. The primary endpoint was to obtain a target volume dose of ≥ 120 Gy in 9/10 patients within a cohort. Results: Twelve patients were treated (male 10; median age, 66.5 years (IQR, [64.3–71.7])) with a median tumor diameter of 2.7 cm (IQR, [2.1–4.0]). At a treatment volume absorbed dose of 90 Gy, the primary endpoint was met with a median absorbed target volume dose of 138 Gy (IQR, [127–145]). No local recurrences were found within 1-year follow-up. Conclusion: Adjuvant (super-)selective infusion of 166Ho-MS after RFA for the treatment of HCC can be administered safely at a dose of 90 Gy to the treatment volume while reaching a dose of ≥ 120 Gy to the target volume and may be a favorable adjuvant therapy for HCC lesions 2–5 cm. Trial registration: NCT03437382.

Original languageEnglish
Pages (from-to)2085-2097
Number of pages13
JournalEuropean journal of nuclear medicine and molecular imaging
Issue number7
Early online date2024
Publication statusPublished - Jun 2024


  • Adjuvant therapy
  • Dose-escalation study
  • Hepatocellular carcinoma
  • Holmium-166
  • Radiofrequency ablation
  • Trans-arterial radioembolization

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