The incidence of primary liver cancers continues to increase in the United States
and worldwide. The majority of patients with primary liver cancer are not
candidates for curative therapies such as surgical resection or orthotopic liver
transplantation due to tumor size, vascular invasion, or underlying
comorbidities. Therefore, while primary liver cancer is the sixth-most common
cancer diagnosis worldwide, it represents the second leading cause of
cancer-related deaths. Radiotherapy traditionally played a limited role in the
treatment of primary liver cancer due to concerns over hepatic tolerance and the
inability to deliver a tumoricidal dose of radiotherapy while still sparing
normal hepatic parenchyma. However, the development of modern radiotherapy
techniques has made liver-directed radiotherapy a safe and effective treatment
option for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. An
increasing body of literature has demonstrated the excellent local control and
survival rates associated with liver-directed radiotherapy. These data include
multiple radiotherapy techniques and modalities, including stereotactic body
radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and charged
particle therapy, including proton therapy. In this review, we discuss the
development of liver-directed radiotherapy and evidence in support of its use,
particularly in patients who are not candidates for resection or orthotopic
liver transplantation. We also discuss future directions for its role in the
management of primary liver cancers.