External beam radiation therapy for hepatocellular carcinoma: Potential of intensity-modulated and image-guided radiation therapy

External beam radiotherapy has historically played a minor role in the primary treatment of hepatocellular carcinoma. Although there is evidence for tumor response to external beam radiotherapy and despite the fact that a radiation dose-response relationship has been established, the limited radiation tolerance of the adjacent normal liver has prohibited wider use of radiation therapy in this disease. Recent technological and conceptual developments in the field of radiation therapy - such as intensity-modulated radiation therapy, image-guided radiation therapy, and stereotactic body radiation therapy - have the potential to improve radiation treatments by conforming the delivered radiation dose distribution tightly to the tumor or target volume outline while sparing normal liver tissue from high-dose radiation. Image guidance allows for a reduction of added (normal tissue) safety margins designed to account for interfraction patient and target setup variability, and stereotactic targeting will further reduce residual target setup uncertainty. Combining improvements in tumor targeting with normal tissue sparing, radiation dose delivery will enable clinically effective and safe radiation delivery for liver tumors such as hepatocellular carcinoma. This article reviews the role of radiotherapy for hepatocellular carcinoma; presents modern radiation therapy modalities and concepts such as intensity-modulated, image-guided, and stereotactic body radiation therapy; and hypothesizes about their future effect on primary treatment alternatives.