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Original Article Recent update of proton beam therapy for hepatocellular carcinoma: A systematic review and meta-analysis
Sun Hyun Bae1*orcid , Won Il Jang2*orcid , Hanna Rahbek Mortensen3orcid , Britta Weber3orcid , Mi Sook Kim2orcid , Morten Høyer3orcid

DOI: https://doi.org/10.17998/jlc.2024.06.26 [Accepted]
Published online: July 4, 2024
1Department of Radiation Oncology, Soonchunhyang University College of Medicine, Bucheon, Korea
2Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
3Danish Center for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark
Corresponding author:  Morten Høyer,
Email: hoyer@aarhus.rm.dk
Received: 16 May 2024   • Revised: 27 May 2024   • Accepted: 26 June 2024
Sun Hyun Bae and Won Il Jang contributed equally to this study as co-first authors.
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Backgrounds/Aims
Although access to proton beam therapy (PBT) is limited worldwide, its use for the treatment of hepatocellular carcinoma (HCC) is gradually increasing with the expansion of new facilities. Therefore, we conducted a systematic review and meta-analysis to investigate the updated evidence of PBT for HCC.
Methods
The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched for studies that enrolled patients with liver-confined HCC that were treated with PBT for a cure up to February 2024.
Results
A total of 1858 HCC patients receiving PBT from 22 studies between 2004 and 2023 were selected for this meta-analysis. The median proportion of Child-Pugh class A was 86% (range: 41–100%), and the median tumor size was 3.6 cm (range: 1.2–9 cm). The median total dose ranged from 55 GyE to 76 GyE (median, 69 GyE). The pooled rates of 3- and 5-year local progression-free survival after PBT were 88% (95% confidence interval [CI], 85–91%) and 86% (95% CI, 82–90%), respectively. The pooled 3- and 5-year overall rates were 60% (95% CI, 54–66%) and 46% (95% CI, 38–54%), respectively. The pooled rates of grade 3 hepatic toxicity, classic radiation-induced liver disease (RILD), and non-classic RILD were 1%, 2%, and 1%, respectively.
Conclusions
The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other radiotherapy modalities. However, further studies are needed to identify the subgroups that will benefit from PBT.


JLC : Journal of Liver Cancer