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This study evaluated the effect of transcatheter arterial Chemoembolization combined with external beam radiotherapy on the response rates and survival of patients with unresectable hepato-cellular carcinoma. Transcatheter arterial Chemoembolization is frequently used for the treatment of this cancer, but complete or massive necrosis is seldom observed. Historically, radiotherapy for hepatocellular carcinoma has yielded poor long-term survival. Multimodality therapy has been initiated in an effort to improve survival statistics.We retrospectively studied 203 patients with unresectable hepatocellular carcinoma, who were free of tumor thrombus, lymph node involvement, or extrahepatic metastasis based on computed tomography scans of the chest and abdomen. Among the 203 patients who received transcatheter arterial Chemoembolization as initial therapy, 54 also received combination therapy with external beam radiotherapy. Tumor response rate, survival, and failure patterns were analyzed and compared between the two groups.Objective responses (complete and partial responses) on computed tomography study were observed in 31% and 76% of patients in the non-radiotherapy and radiotherapy groups, respectively. Overall survival rates in the patients in the radiotherapy group were 71.5%, 42.3%, and 24.0% at 1, 2, and 3 years, respectively, improved over the non-radiotherapy group rates of 59.6%, 26.5%, and 11.1% at 1, 2, and 3 years, respectively. Intrahepatic failure was lower in the radiotherapy group than in the non-radiotherapy group, but the difference was not significant. Side effects from radiotherapy were common, but rarely severe.This retrospective study suggests that the outcome of unresectable hepatocellular carcinoma can be influenced by radiation therapy, but a prospective randomized trial would be necessary to draw definitive conclusions.