Clinical Trial

. 2024 Jul 8;24(1):813.

doi: 10.1186/s12885-024-12504-2.

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC)

Alan Wigg^{1

2}, Jonathan Tibballs³, Richard Woodman⁴, Katherine Stuart⁵, Hien Le^{6

7}, Stuart K Roberts⁸, John K Olynyk⁹, Simone I Strasser^{10

11}, Michael Wallace³, Jarad Martin¹², Annette Haworth¹¹, Nicholas Hardcastle^{13

14}, Kee Fong Loo¹⁵, Colin Tang³, Yoo Young Lee⁵, Julie Chu¹³, Richard De Abreu Lourenco¹⁶, Adam Koukourou¹⁵, Diederick De Boo¹⁷, Kate McLean⁵, Jackie Buck¹⁸, Rohit Sawhney¹⁹, Amanda Nicoll¹⁹, Anouk Dev¹⁷, Marnie Wood²⁰, Alicia Braund²¹, Martin Weltman²², Richard Khor²³, Miriam Levy²⁴, Tim Wang²⁵, Michael Potter²⁶, James Haridy²⁷, Ashok Raj²⁷, Oliver Duncan⁹, Amany Zekry²⁸, Natalie Collier²⁹, James O'Beirne³⁰, Catherine Holliday³¹, Yuvnik Trada³², Jaw Tronidjaja²⁶, Jacob George^{11

33}, David Pryor⁵

Affiliations

¹ Southern Adelaide Local Health Network, Adelaide, Australia. alan.wigg@sa.gov.au.
² Flinders University of South Australia, Adelaide, Australia. alan.wigg@sa.gov.au.
³ Sir Charles Gardiner Hospital, Perth, Australia.
⁴ Flinders University of South Australia, Adelaide, Australia.
⁵ Princess Alexandra Hospital, Brisbane, Australia.
⁶ Central Adelaide Local Health Network, Adelaide, Australia.
⁷ University of South Australia, Adelaide, Australia.
⁸ The Alfred Hospital, Melbourne, Australia.
⁹ Fiona Stanley Hospital, Perth, Australia.
¹⁰ Royal Prince Alfred Hospital, Sydney, Australia.
¹¹ University of Sydney, Sydney, Australia.
¹² University of Newcastle, Newcastle, England.
¹³ Peter MacCallum Cancer Centre, Melbourne, Australia.
¹⁴ Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
¹⁵ Southern Adelaide Local Health Network, Adelaide, Australia.
¹⁶ University of Technology Sydney, Sydney, Australia.
¹⁷ Monash Health, Melbourne, Australia.
¹⁸ Trans-Tasman Radiation Oncology Group, Waratah, Australia.
¹⁹ Eastern Health, Melbourne, Australia.
²⁰ Royal Brisbane and Women's Hospital, Brisbane, Australia.
²¹ Gold Coast University Hospital, Gold Coast, Australia.
²² Nepean Hospital, Sydney, Australia.
²³ Austin Health, Melbourne, Australia.
²⁴ Liverpool Hospital, Sydney, Australia.
²⁵ Westmead Hospital, Sydney, Australia.
²⁶ John Hunter Hospital, Newcastle, Australia.
²⁷ Royal Melbourne Hospital, Melbourne, Australia.
²⁸ St George Hospital, Sydney, Australia.
²⁹ Wollongong Hospital, Wollongong, Australia.
³⁰ Sunshine Coast University Hospital, Sunshine Coast, Australia.
³¹ Centre for Community-Driven Research, Sydney, Australia.
³² Calvary Mater, Newcastle, Australia.
³³ Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, Sydney, Australia.

PMID: 38973009
PMCID: PMC11229272
DOI: 10.1186/s12885-024-12504-2

Clinical Trial

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC)

Alan Wigg et al. BMC Cancer. 2024.

. 2024 Jul 8;24(1):813.

doi: 10.1186/s12885-024-12504-2.

Authors

Affiliations

¹ Southern Adelaide Local Health Network, Adelaide, Australia. alan.wigg@sa.gov.au.
² Flinders University of South Australia, Adelaide, Australia. alan.wigg@sa.gov.au.
³ Sir Charles Gardiner Hospital, Perth, Australia.
⁴ Flinders University of South Australia, Adelaide, Australia.
⁵ Princess Alexandra Hospital, Brisbane, Australia.
⁶ Central Adelaide Local Health Network, Adelaide, Australia.
⁷ University of South Australia, Adelaide, Australia.
⁸ The Alfred Hospital, Melbourne, Australia.
⁹ Fiona Stanley Hospital, Perth, Australia.
¹⁰ Royal Prince Alfred Hospital, Sydney, Australia.
¹¹ University of Sydney, Sydney, Australia.
¹² University of Newcastle, Newcastle, England.
¹³ Peter MacCallum Cancer Centre, Melbourne, Australia.
¹⁴ Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
¹⁵ Southern Adelaide Local Health Network, Adelaide, Australia.
¹⁶ University of Technology Sydney, Sydney, Australia.
¹⁷ Monash Health, Melbourne, Australia.
¹⁸ Trans-Tasman Radiation Oncology Group, Waratah, Australia.
¹⁹ Eastern Health, Melbourne, Australia.
²⁰ Royal Brisbane and Women's Hospital, Brisbane, Australia.
²¹ Gold Coast University Hospital, Gold Coast, Australia.
²² Nepean Hospital, Sydney, Australia.
²³ Austin Health, Melbourne, Australia.
²⁴ Liverpool Hospital, Sydney, Australia.
²⁵ Westmead Hospital, Sydney, Australia.
²⁶ John Hunter Hospital, Newcastle, Australia.
²⁷ Royal Melbourne Hospital, Melbourne, Australia.
²⁸ St George Hospital, Sydney, Australia.
²⁹ Wollongong Hospital, Wollongong, Australia.
³⁰ Sunshine Coast University Hospital, Sunshine Coast, Australia.
³¹ Centre for Community-Driven Research, Sydney, Australia.
³² Calvary Mater, Newcastle, Australia.
³³ Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, Sydney, Australia.

PMID: 38973009
PMCID: PMC11229272
DOI: 10.1186/s12885-024-12504-2

Abstract

Background: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking.

Methods: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses.

Discussion: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research.

Trial registration: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Keywords: Early-stage hepatocellular carcinoma; SABR; SBRT; Stereotactic ablative radiotherapy; Thermal ablation; Transarterial therapies; Treatment stage migration.

PubMed Disclaimer

Conflict of interest statement

Nicholas Hardcastle receives research grant funding from Varian Medical Systems and is a paid consultant of SeeTreat Medical.

Figures

**Fig. 1**
TROG 21.07 SOCRATES HCC study schema

See this image and copyright information in PMC

Cited by

Report from the 26th Annual Western Canadian Gastrointestinal Cancer Consensus Conference on Hepatocellular and Biliary Tract Cancer, Saskatoon, Saskatchewan, 17-18 October 2024.
Ravi D, Ahmed S, Anderson B, Anderson B, Brunet B, Chalchal H, Elangovan A, Geller G, Gordon V, Gowrishankar B, Hardy E, Iqbal M, Le D, Lee-Ying R, Mahmood S, Mulder K, Nashed M, Newman K, Ogaick M, Pareek V, Rauw J, Wong R, Zaidi A. Ravi D, et al. Curr Oncol. 2025 Jul 10;32(7):398. doi: 10.3390/curroncol32070398. Curr Oncol. 2025. PMID: 40710208 Free PMC article.

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A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC)

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A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC)

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