Individualised dosimetry for holmium-166 RE in patients with unresectable hepatocellular carcinoma; a multi-centre, interventional, non-randomised, non-comparative, open label, phase II study: RHEPaiR.

INTRODUCTION: Radioembolisation (RE) is gaining traction as a robust treatment option for patients with hepatocellular cancer (HCC) across all cancer stages. RE allows the delivery of targeted high-dose radiation directly to tumours, with relative sparing of the surrounding liver tissue. Traditionally, radiation has been delivered using 90Yttrium ([90Y]Y)-labelled microspheres, either glass or resin. The success of RE is dependent on the dose delivered to the tumour. When using [90Y]Y microspheres, dose prediction is calculated through a 99mTechnitium ([99mTc]Tc)-macroaggregated albumin (MAA) scan, which allows the calculation of the dose to be administered to the tumour. However, [99mTc]Tc-MAA is not a true surrogate of [90Y]Y microspheres, and this will impact on the final dose delivered. [166Ho]Ho, like [90Y]Y, is a beta emitter but unlike [90Y]Y also emits gamma-radiation, allowing for quantitative nuclear imaging. The primary aim of this pilot study was to investigate the safety and efficacy of dosimetry-based individualised 166Holmium ([166Ho]Ho-RE) in patients with HCC. METHODS AND ANALYSIS: 15 eligible participants will be recruited to receive [166Ho]Ho-RE. The primary objective is to establish the toxicity profile of dosimetry-based individualised [166Ho]Ho-RE. The secondary objective is to assess efficacy as measured by modified Response Evaluation Criteria in Solid Tumours (mRECIST) and Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria. Additional exploratory objectives include quality of life assessment and identification of a radiomic signature of response. The results from this study will be combined with the prospective iHEPAR study to form a larger analysis. ETHICS AND DISSEMINATION: The study has received approval from the East Midlands-Nottingham 1 Research Ethics Committee-approval number 23/EM/0239. The study will be performed in compliance with the Declaration of Helsinki and the principles of Good Clinical Practice. Signed informed consent will be obtained from each patient before study entry. The results will be disseminated through publication in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT06302400.