Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide.1 Although the incidence of this cancer is rising in many countries of the developed world, most deaths occur in Asia and the developing world. Traditionally, external beam radiotherapy has had Selleckchem BTK inhibitor a very limited role in the treatment

of HCC and is rarely considered in current treatment recommendations of the major Asia–Pacific regions, American and European societies.2,3 There are many reasons for the current lack of interest in radiotherapy. The discouraging early experience with radiotherapy for HCC was a key factor leading to the current widespread belief that HCC is not a ‘radiosensitive’ tumor and that radiotherapy is too ‘toxic’ for the liver. During this era, large HCC were treated with large volume or whole liver radiotherapy, which was associated with high rates of radiation-induced liver disease and poor tumor response rates. As will

be discussed, an understanding of the relationship between the volume of normal tissue (liver) irradiated and tolerable dose is necessary. We are usually mainly concerned about the late radiation effects. Recent developments have concentrated on means of identifying and treating small volumes, because tolerance of liver to radiation is very volume dependant. These developments include the use of radioactive 90Y microspheres locally introduced, stereotactic JQ1 mw radiotherapy, the use of intensity modulated X-ray beams and the more exotic and expensive heavy Ureohydrolase ion therapy. Other means of delivering a local effect include surgery, chemotherapy and percutaneous techniques for tumor ablation. In our view, the roles of radiotherapy, especially

external beam fractionated treatment using standard multifield treatment techniques and modern 3-D computer planning, have been undervalued. It is essential that the radiobiological base for treatment be understood. To help address this problem, the current radiobiology data for HCC and normal liver have been reviewed. These data have been used to describe radiosensitivity of HCC and normal liver and the fundamental concepts of liver tolerance and growth rates of HCC. Tumor control probability when conventional fractionated external beam radiotherapy was used was also examined. The medical published work was reviewed using a computer-based Medline search supplemented by relevant references from primary articles (http://medline.cos.com). These searches were particularly directed to volume doubling times (Tvol) and growth rate of HCC, radiosensitivity of HCC and normal liver and the radiobiology of normal tissue responses. Graphs and associated calculations were generated using Mathcad 2001 software (MathSoft, Cambridge, MA, USA).