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

Journal: Cardiovascular and Interventional Radiology
Year of publication: 2022
Page: Online ahead of print

P. Hendriks, D.D.D. Rietbergen, A.R. van Erkel, M.J. Coenraad, M.J. Arntz, R.J. Bennink, A.E. Braat, A.S.L.P. Crobach, O.M. van Delden, T. van der Hulle, H.J. Klümpen, R.W. van der Meer, J.F.W. Nijsen, C.S.P. van Rijswijk, J. Roosen, B.N. Ruijter, F. Smit, M.K. Stam, R.B. Takkenberg, M.E. Tushuizen, F.H.P. van Velden, L.F. de Geus-Oei, M.C. Burgmans & Dutch Hepatocellular Cholangiocarcinoma Group

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.