Historically, the use of external-beam radiotherapy for hepatocellular carcinoma (HCC) has been limited by toxicity to the uninvolved liver and surrounding structures. Advances in photon radiotherapy have improved dose conformality to the tumor and facilitated dose escalation, a key contributor to improved HCC radiation treatment outcomes. However, despite these advances in photon radiotherapy, significant volumes of liver still receive low doses of radiation that can preclude dose escalation, particularly in patients with limited functional liver reserves. By capitalizing on the lack of exit dose along the beam path beyond the tumor and higher biological effectiveness, charged-particle therapy offers the promise of maximizing tumor control via dose escalation without excessive liver toxicity. In this review, we discuss the distinctive biophysical attributes of both proton and carbon ion radiotherapy, particularly as they pertain to treatment of HCC. We also review the available literature regarding clinical outcomes and the toxicity of using charged particles for the treatment of HCC.
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