Potential and future strategies for radiotherapy in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) continues to be one of the worst cancer conditions worldwide, being the sixth most common cancer and associated with a 5-year overall survival rate of only 5% (1). Surgery, either in terms of local resection or liver transplant, is still the treatment of choice, with 5-year survival rates of 30–70% (2). However, o 20% of patients qualify for this treatment because of intrahepatic cancer multi-focality, extrahepatic tumour manifestations, inadequate liver function and/or involvement of vascular or biliary structures. Alternative local treatment options for localized HCC include radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), radiotherapy and transarterial chemoembolization (TACE). Two randomized trials have shown that TACE leads to an improved survival compared with best supportive care (3, 4), but its efficacy is modest and restricted to patients without portal vein thrombosis. The use of radiotherapy for locoregional treatment of HCC has long been studied. The relatively low tolerance of the whole liver to radiotherapy traditionally prohibited the application of sufficiently high doses to control local tumour growth, leading to a general notion of HCC as a 'radioresistant condition'. However, radiotherapy underwent major technological improvements during the last decades including diagnostic imaging, radiotherapy planning techniques [three-dimensional (3D) conformal radiotherapy, intensity-modulated radiother-apy and stereotactic body radiosurgery], image-guided radio-therapy to detect to the exact position of the tumour at the time of treatment along with respiration-gated radiotherapy to account for liver movements because of breathing. Moreover, radiotherapy with highly conformal protons and carbon ions is increasingly available. All these technological advances allow to treat liver tumours much more precisely, thereby minimizing dose to uninvolved liver tissue and other organs at risk. Because of the opening of the therapeutic window, radiotherapy has lately gained increased consideration for treatment of HCC, specifically in cases of failures to standard treatments [recently reviewed in (5)]. In this issue of Liver International, Seong et al. (6) report on the practice patterns and outcome in 398 radiation-treated HCC patients in Korea. Data from 10 Korean institutions were collected. The vast majority of patients have been treated by 3D-conformal radiotherapy after failure of TACE. The paper confirms the results of a previous report of the authors on a subset of patients from one single institution, where multi-variate analysis revealed increased radiation dose to be an independent prognostic factor for improved overall survival (7). This is also in line with the results of the University of Michigan group, having …