Journal of Liver Cancer

Review Article

The role of radiotherapy in the management of combined hepatocellular-cholangiocarcinoma: current evidence and future perspectives: Seo Hee Choi, Woong Sub Koom, Ik Jae Lee; J Liver Cancer. 2026;26(1):55-64. Published online March 5, 2026; DOI: https://doi.org/10.17998/jlc.2026.03.04

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Abstract PDF: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare and highly aggressive hybrid malignancy characterized by a poor prognosis and high recurrence rates due to its dual histological nature. In the absence of established standard-of-care protocols, clinical management strategies are frequently extrapolated from the guidelines for its components, hepatocellular carcinoma and intrahepatic cholangiocarcinoma (iCCA). This review evaluates the evolving role of radiotherapy (RT) as an integral part of the multidisciplinary care for cHCC-CCA. Adjuvant RT may be considered for patients exhibiting high-risk pathological features, such as positive or close resection margins, lymphovascular invasion, and perineural invasion. For unresectable disease unfeasible for surgery or transarterial therapies, definitive RT using intensified doses, analogous to iCCA protocols, is employed to improve local control. High-precision modalities, particularly particle therapies such as proton or carbon ion RT, are emphasized as preferred options for delivering ablative doses while minimizing toxicity and preserving functional liver reserve. Furthermore, preliminary clinical evidence suggests a potential synergy between RT and immune checkpoint inhibitors, with reported cases demonstrating complete responses or successful conversion to curative-intent resection. While current evidence remains limited to retrospective cohorts and case series, the strategic integration of precision RT offers a rational pathway for optimizing outcomes in cHCC-CCA, necessitating further prospective validation.

Original Article

Recent update of proton beam therapy for hepatocellular carcinoma: a systematic review and meta-analysis: Sun Hyun Bae, Won Il Jang, Hanna Rahbek Mortensen, Britta Weber, Mi Sook Kim, Morten Høyer; J Liver Cancer. 2024;24(2):286-302. Published online July 4, 2024; DOI: https://doi.org/10.17998/jlc.2024.06.26

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10 Citations

Abstract PDF Supplementary Material

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 metaanalysis 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 1,858 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, 1.2-9.0). The median total dose ranged from 55 GyE to 76 GyE (median, 69). 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 radiationinduced 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.

Citations

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