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Expert consensus on clinical trials for use of systemic therapy in patients with hepatocellular carcinoma undergoing surgical and locoregional therapies.

Created on 25 Sep 2026

Authors

Mark Yarchoan, Josep M Llovet, Robin Kate Kelley, Richard Finn, Neehar D Parikh, Parissa Tabrizian, Adam M Burgoyne, Vatche G Agopian, Nina N Sanford, Hop S Tran Cao, Siddharth A Padia, Arndt Vogel, Robert J Lewandowski, Garcia-Reyes Kirema, Ruitao Lin, Neil Mehta, Gonzalo Sapisochin, Adam Yopp, Augusto Villanueva, Karim Halazun, David J Pinato, Edward Kim, Julie K Heimbach, Anjana Pillai, Riad Salem, Anthony El-Khoueiry, Amit G Singal

Published in

Gut. Sep 24, 2026. Epub Sep 24, 2026.

Abstract

Advances in systemic therapy for advanced hepatocellular carcinoma (HCC) have fuelled a growing interest in evaluating these therapies in earlier stages of disease. However, trial design remains challenging due to the marked clinical and biological heterogeneity of early-stage and intermediate-stage HCC.
A multidisciplinary group of cancer experts was convened by the HCC-Live Consortium to discuss inclusion criteria, risk stratification, treatment arms and appropriate endpoints of trials evaluating perioperative and combination therapies in patients with HCC.
Consensus statements were defined as those obtaining >70% approval by panellists.
The panel achieved consensus regarding nine consensus statements for neoadjuvant or perioperative systemic therapy and nine statements for combination locoregional plus systemic therapy. Statements emphasised recruiting carefully selected patient populations, employing treatment strategies and duration that balance efficacy with safety and using clinically relevant endpoints. Trials evaluating neoadjuvant/perioperative approaches should include patients at the highest risk of recurrence, with a recommended primary outcome of 2-year event-free survival using restricted mean survival time. Trials evaluating combination therapies should include a homogeneous patient population and use an appropriate comparator arm that aligns with clinical practice. Specifically, systemic therapy was the recommended comparator arm for patients with larger tumour burden and locally advanced disease. The recommended primary outcome for combination trials was progression-free survival and overall survival, with an alpha-recycling strategy. Secondary endpoints are essential to inform clinical applicability.
Optimal design of HCC trials is important to rigorously evaluate the role of systemic therapy in patients undergoing surgical resection or in combination with locoregional therapy.

PMID:
42785981
Bibliographic data and abstract were imported from PubMed on 25 Sep 2026.

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