Role and Future Directions of External Beam Radiotherapy for Primary Liver Cancer

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.