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.

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.

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.

Clinicaltrials.gov NCT06302400.

Gastroenteropancreatic neuroendocrine tumours (GEP NET) are malignant neoplasms that impact survival. Somatostatin analogues (SSA) are used for treating hormonal symptoms caused by GEP NET and have antiproliferative effects. They are used as first-line therapy in patients with advanced GEP NET, but disease control is limited to a median progression-free survival (mPFS) of 14–32 months. Second-line treatment options include targeted therapy (everolimus or sunitinib), or peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATATE. In patients suffering from a NET-related hormonal syndrome, SSA is generally continued life-long. However, there is no consensus on whether it is beneficial to continue SSA in non-functional NET upon disease progression. Due to the ongoing activity of the somatostatin receptor pathway in GEP NET progressing on first-line SSA, we hypothesise that SSA have an added efficacy in second-line therapy.

The SAUNA trial is an international, multicentre, open-label, randomised, controlled, pragmatic clinical trial. 270 patients with advanced, non-functional GEP NET and progression under first-line SSA will be included in substudy 1 (PRRT; n=142) or substudy 2 (targeted therapy (everolimus/sunitinib); n=128) per investigator’s choice of second-line therapy and will be randomised (1:1) per substudy between SSA continuation or SSA withdrawal arms. Co-primary endpoints are the difference in progression-free survival (PFS) according to the RECIST (Response Evaluation Criteria In Solid Tumours) V.1.1 criteria and difference in time to deterioration (TTD) in quality of life (QoL) per substudy after initiating second-line therapy with or without SSA. Secondary endpoints include the PFS rate at 18 months, the difference in pooled PFS and TTD combining both substudies, overall survival, response rates, QoL, costs, cost-effectiveness and toxicity. The study design was developed in cooperation with the Belgium and Dutch patient organisations.

The study has been approved on 31 May 2023 by the Ethical Committees and Regulatory Authorities of the concerned member states (EU CT number 2022-502703-30-00). Both the trial management group and the steering committee will oversee good governance of this trial. Results of the study will be published in peer-reviewed international journals and presented at international conferences.

NCT05701241.