Overall Survival Among Patients With Hepatocellular Carcinoma Treated With External Beam Radiation Therapy: Individual Patient Data Outcomes From a Multinational Cohort

A Andrew M. Moon (Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC) T Ted K. Yanagihara (Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC) L Laura A. Dawson (Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada) J Jeong Il Yu (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea) T Theodore S. Lawrence T Tae Hyun Kim M Michael Yan (Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada) H Hiromitsu Iwata N Nima Nabavizadeh (Department of Radiation Medicine, School of Medicine, Oregon Health & Science University, Portland, OR) S Smith Apisarnthanarax (Department of Radiation Oncology, University of Washington, Seattle, WA) E Emma M. Dunne (Department of Radiation Oncology, British Columbia Cancer—Vancouver, Vancouver, BC, Canada) M Michael I. Lock (Department of Radiation Oncology, London Health Sciences Centre, London, ON, Canada) M Michael D. Chuong (Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL) C Chi Leung Chiang (Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong KongChina,) M Marta Scorsetti (Department of Biomedical Sciences, Humanitas University, Milan, Italy) N Norio Katoh S Shirin Sioshansi (Department of Radiation Oncology, Brown University Health Cancer Institute, Providence, RI) K Kazushi Numata (Gastroenterological Center, Yokohama City University Medical Center) H Howard Yu-hao Liu (Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, QLD, Australia) H Hideki Iwamoto M Masaru Wakatsuki Y Yixing Chen E Erqi L. Pollom (Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA) E Eleni Gkika (Department of Radiation Oncology University Hospital Bonn Bonn Germany) S Salma K. Jabbour (Department of Radiation Oncology, Rutgers Cancer Institute, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ) P Pablo Munoz-Schuffenegger (Radiation Oncology Unit, Department of Hematology—Oncology, Pontificia Universidad Catolica de Chile, Santiago, Chile) D Debnarayan Dutta (Department of Radiation Oncology, Radiation Oncology, Amrita Institute of Medical Sciences, Kochi, India) C Carla Hajj (Radiation Oncology Department, Cleveland Clinic Abu Dhabi Cancer Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates) M Masayuki Ueno C Christopher L. Hallemeier (Department of Radiation Oncology, Mayo Clinic, Rochester, MN) A Aharon M. Feldman (Department of Radiation Oncology, Henry Ford Health, Detroit, MI) A Alejandra Méndèz Romero (Department of Radiotherapy, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands) X Xianming Tan M Meritxell Molla (Radiation Oncology Department, Hospital Clínic Barcelona, Barcelona, Spain) J Joel E. Tepper (Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC) F Ferran Torres M Maria Reig A Alanah M. Bergman C Christopher Crane K Kyle C. Cuneo N Natalie Grindrod A Anca-Ligia Grosu R Rodrigo El Far C Ciro Franzese A Akihiro Funaoka M Marissa Gilbert S Satoshi Itasaka S Sung Uk Lee Y Yoo Young Dominique Lee J Joel Mases H Hiroyuki Ogino V Vera Qu H Hee Chul Park R Ramtin Rahmani L Lee Ann Shing T Tomotake Shirono T Teodor Stanescu K Kanokphorn Thonglert W Wilhelm den Toom Y Yusuke Uchinami Z Zhaochong Zeng

Abstract

PURPOSE External beam radiation therapy (EBRT) has gained delayed acceptance as a recommended first-line treatment modality for patients with hepatocellular carcinoma (HCC), given limited evidence that it improves overall survival (OS). We analyzed individual patient data (IPD) from an international cohort to assess OS among patients with HCC treated with EBRT. METHODS We performed a systematic review of publications that assessed EBRT, met prespecified technical standards for HCC, and reported OS (search date December 15, 2022). Corresponding authors were invited to submit IPD for the study. We performed Kaplan-Meier survival analyses to determine OS and restricted mean survival time (RMST) stratified by Barcelona Clinic Liver Cancer (BCLC) stage and treatment status (ie, treatment-naïve and experienced). We performed random effects Cox proportional hazards modeling to assess clinical characteristics associated with OS. RESULTS Data were provided on 4,913 patients treated with EBRT with a median follow-up time of 5.0 years. The median OS was 6.8 years (95% CI, 5.7 to 8.7) for BCLC-0 and 4.6 years (95% CI, 4.1 to 5.1) for BCLC-A. Among treatment-naïve patients, the median OS was not reached (95% CI, 8.6 to not reached) for BCLC-0 and was 5.4 years (95% CI, 4.5 to 6.7) for BCLC-A. In multivariable models, more advanced BCLC stage, higher tumor burden, worse performance status, and Child-Pugh class B or C were associated with a higher risk of mortality. Ablative radiation dose and more recent year of treatment were associated with a reduced risk of death. CONCLUSION To our knowledge, this study represents the largest multinational cohort of patients with HCC treated with EBRT. OS outcomes with EBRT for very early- and early-stage HCC appear to be comparable with resection, thermal ablation, and other ablative locoregional therapies. These data support the inclusion of EBRT in the BCLC HCC clinical decision-making process.

Article Details

Volume / Issue Vol. 44, Issue 19
Published July 01, 2026
Pages 1784-1797
ISSN 0732-183X
Publisher Lippincott Williams & Wilkins

Journal Info

Journal of Clinical Oncology

Lippincott Williams & Wilkins

ISSN: 0732-183X Health Sciences

Authors (61)

A

Andrew M. Moon

Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC

T

Ted K. Yanagihara

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC

L

Laura A. Dawson

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

J

Jeong Il Yu

Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

T

Theodore S. Lawrence

T

Tae Hyun Kim

M

Michael Yan

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

H

Hiromitsu Iwata

N

Nima Nabavizadeh

Department of Radiation Medicine, School of Medicine, Oregon Health & Science University, Portland, OR

S

Smith Apisarnthanarax

Department of Radiation Oncology, University of Washington, Seattle, WA

E

Emma M. Dunne

Department of Radiation Oncology, British Columbia Cancer—Vancouver, Vancouver, BC, Canada

M

Michael I. Lock

Department of Radiation Oncology, London Health Sciences Centre, London, ON, Canada

M

Michael D. Chuong

Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL

C

Chi Leung Chiang

Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong KongChina,

M

Marta Scorsetti

Department of Biomedical Sciences, Humanitas University, Milan, Italy

N

Norio Katoh

S

Shirin Sioshansi

Department of Radiation Oncology, Brown University Health Cancer Institute, Providence, RI

K

Kazushi Numata

Gastroenterological Center, Yokohama City University Medical Center

H

Howard Yu-hao Liu

Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, QLD, Australia

H

Hideki Iwamoto

M

Masaru Wakatsuki

Y

Yixing Chen

E

Erqi L. Pollom

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA

E

Eleni Gkika

Department of Radiation Oncology University Hospital Bonn Bonn Germany

S

Salma K. Jabbour

Department of Radiation Oncology, Rutgers Cancer Institute, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ

P

Pablo Munoz-Schuffenegger

Radiation Oncology Unit, Department of Hematology—Oncology, Pontificia Universidad Catolica de Chile, Santiago, Chile

D

Debnarayan Dutta

Department of Radiation Oncology, Radiation Oncology, Amrita Institute of Medical Sciences, Kochi, India

C

Carla Hajj

Radiation Oncology Department, Cleveland Clinic Abu Dhabi Cancer Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

M

Masayuki Ueno

C

Christopher L. Hallemeier

Department of Radiation Oncology, Mayo Clinic, Rochester, MN

A

Aharon M. Feldman

Department of Radiation Oncology, Henry Ford Health, Detroit, MI

A

Alejandra Méndèz Romero

Department of Radiotherapy, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands

X

Xianming Tan

M

Meritxell Molla

Radiation Oncology Department, Hospital Clínic Barcelona, Barcelona, Spain

J

Joel E. Tepper

Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC

F

Ferran Torres

M

Maria Reig

A

Alanah M. Bergman

C

Christopher Crane

K

Kyle C. Cuneo

N

Natalie Grindrod

A

Anca-Ligia Grosu

R

Rodrigo El Far

C

Ciro Franzese

A

Akihiro Funaoka

M

Marissa Gilbert

S

Satoshi Itasaka

S

Sung Uk Lee

Y

Yoo Young Dominique Lee

J

Joel Mases

H

Hiroyuki Ogino

V

Vera Qu

H

Hee Chul Park

R

Ramtin Rahmani

L

Lee Ann Shing

T

Tomotake Shirono

T

Teodor Stanescu

K

Kanokphorn Thonglert

W

Wilhelm den Toom

Y

Yusuke Uchinami

Z

Zhaochong Zeng