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Review | Open Access

Hepatoma Research

Hall et al. Hepatoma Res. 2026;12:20 DOI:10.20517/2394-5079.2025.70

Yttrium-90 combination therapies in hepatocellular
carcinoma: current evidence and future directions

Bailey Hall, Zachary Ohs, Mario Dervishi, Alex Stevens, Christopher Sutter, Jon Davidson

Keywords:
Yttrium-90,
radioembolization,
hepatocellular carcinoma,
systemic therapy,
multi-kinase inhibitors,
immune checkpoint
inhibitors, combination
therapy
Citation: Hall B, Ohs Z,
Dervishi M, Stevens A,
Sutter C, Davidson J.
Yttrium-90 combination
therapies in hepatocellular
carcinoma: current evidence
and future directions.
Hepatoma Res. 2026;12:20.
https://dx.doi.org/10.20517
/2394-5079.2025.70 Abstract
Yttrium-90 (Y-90) radioembolization, via endovascular delivery of high-dose beta
Received: 18 Sep 2025 radiation microspheres to tumors, is an invaluable locoregional therapy for hepatocellular
First Decision: 17 Dec carcinoma (HCC). Y-90’s limited off-target radiation exposure enables excellent tumor
2025
Revised: 19 Jan 2026 control with a favorable safety profile. Recent developments suggest that combining
Accepted: 16 Mar 2026 targeted radioembolization with systemic treatments, such as molecularly targeted
Published: 29 May 2026 therapies and immune checkpoint inhibitors (ICIs), may offer additive or even synergistic
benefits, thereby enhancing both local tumor response and immune activation. This review
Academic Editors:
Binyan Zhong, Hongping Xia explores the mechanistic rationale, clinical evidence, and therapeutic strategies involving
Copy Editor: Y-90 combination therapies in HCC. Data from phase I, II, and III trials suggest improved
Shu-Yuan Duan outcomes with Y-90 plus ICI combination therapy compared with monotherapy. By
Production Editor: contrast, trials comparing Y-90 and multi-kinase combination inhibitors with monotherapy
Shu-Yuan Duan
have yielded mixed results, highlighting the importance of continued research. Challenges
remain in patient selection, optimal sequencing, and toxicity management. To date, no
randomized clinical trials have directly compared Y-90 alone with Y-90-based
combination therapy, but ongoing trials aim to clarify the role of Y-90 in the evolving
systemic treatment landscape. This review highlights the potential of Y-90 combination
therapies to enhance the multidisciplinary management of HCC and underscores future

Department of Radiology, Division of Vascular and Interventional Radiology, University Hospitals Cleveland Medical Center, Case Western
Reserve University School of Medicine, Cleveland, OH 44106, USA.

Correspondence to: Dr. Bailey Hall, Department of Radiology, Division of Vascular and Interventional Radiology, University Hospitals
Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. E-mail:
Bailey.Hall@uhhospitals.org

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