A Dose Escalation Trial of Radiation Therapy (RT) for Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma (HCC) is one of the leading malignancies in Taiwan. Surgery and local ablative therapy remain the treatment of choice for curative purpose. Transarterial chemoembolization has been the mainstay of intrahepatic control for patients not being candidates for local modalities of treatment. Sorafenib is recently integrated into the treatment options, mainly for intrahepatic or extrahepatic wide spread disease contraindicated for the other modalities. External radiotherapy (RT) has been selectively used for patients with the localized hepatic tumor(s) refractory to the above treatment options. The data from the retrospective studies were biased by the patient selection and uncontrolled comparison with patients not receiving RT. The obstacles for RT to HCC remain unanswered with heterogeneity in dose of radiation and lower tolerance of liver to RT in viral hepatitis carriers. Such a sublethal dose might be associated with unsatisfactory tumor control, intra-/extra-hepatic metastasis, and radiation-induced liver disease in a significant proportion of HCC patients. The purposes of this phase I study are primarily to determine the maximally tolerated dose of RT, and secondarily to evaluate the tumor control, to assess patterns of failure and survival, to analyze the characteristics of radiation-induced liver disease, as well as to collect blood samples for translational research. HCC patients who are hepatitis B virus carriers and graded as Child-Pugh A cirrhosis are enrolled. This dose escalation trial is conducted with the 7-Gy increase in 2 fractions (3.5 Gy per fraction) for a total of four levels, from 42 Gy up to 63 Gy. Conformal RT with three-dimensional design, intensity modulated RT, or volumetric modulated arc therapy is used with the defined dose-volume threshold for normal liver and the other structures. Five patients are treated for each dose level, with dose limiting toxicity in less than 2 patients judged to be acceptable. A minimum of