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Before the sorafenib era, advanced but liver-confined hepatocellular carcinoma (HCC) was treated by liver-directed therapy. Hepatic arterial concurrent chemoradiotherapy (CCRT) has been performed in our group, giving substantial local control but frequent failure. The aim of this study was to analyze patterns of failure and find out predictive clinical factors in HCC treated with a liver-directed therapy, CCRT. A retrospective analysis was done for 138 HCC patients treated with CCRT between May 2001 and November 2009. Protocol-based CCRT was performed with local radiotherapy (RT) and concurrent 5-fluorouracil (5-FU) hepatic arterial infusion chemotherapy (HAIC), followed by monthly HAIC (5-FU and cisplatin). Patterns of failure were categorized into three groups: infield, intrahepatic-outfield and extrahepatic failure. Treatment failure occurred in 34.0% of patients at 3 months after RT. Infield, intrahepatic-outfield and extrahepatic failure were observed in 12 (8.6%), 26 (18.7%) and 27 (19.6%) patients, respectively. Median progression-free survival for infield, outfield and extrahepatic failure was 22.4, 18 and 21.5 months, respectively. For infield failure, a history of pre-CCRT treatment was a significant factor (P = 0.020). Pre-CCRT levels of alpha-fetoprotein and prothrombin induced by vitamin K absence or antagonist-II were significant factors for extrahepatic failure (P = 0.029). Treatment failures after CCRT were frequent in HCC patients, and were more commonly intrahepatic-outfield and extrahepatic failures than infield failure. A history of pre-CCRT treatment and levels of pre-CCRT tumor markers were identified as risk factors that could predict treatment failure. More intensified treatment is required for patients presenting risk factors.

Clinical factors related to recurrence after hepatic arterial concurrent chemoradiotherapy for advanced but liver-confined hepatocellular carcinoma