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The endpoint in cancer research is overall survival. Nonetheless, other potential surrogate endpoints, such as response rate and time to progression, are currently used.

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The design of clinical trials in hepatocellular carcinoma (HCC) is complex because many patients have concurrent liver disease, which can confound the assessment of clinical benefit. There is an urgent need for high-quality trials in this disease. An expert panel was convened by the American Association for the Study of Liver Diseases to develop guidelines that provide a common framework for designing trials to facilitate comparability of results. According to these guidelines, randomized phase 2 trials with a time-to-event primary endpoint, such as time to progression, are pivotal in clinical research on HCC. Survival remains the main endpoint to measure effectiveness in phase 3 studies, whereas time to recurrence is proposed as an appropriate endpoint in the adjuvant setting. Because progression-free survival and disease-free survival are composite endpoints, they are more vulnerable than others in HCC clinical studies and may not be able to capture clinical benefits. Selection of the target population should be based on the Barcelona Clinic Liver Cancer staging system. New drugs should be tested in patients with well-preserved liver function (Child-Pugh A class). Patients assigned to the control arm should receive standard-of-care therapy, that is, chemoembolization for patients with intermediate-stage disease and sorafenib for patients with advanced-stage disease. Further research is needed to incorporate biomarkers and molecular imaging into clinical research in HCC. These surrogate markers may help to enrich study populations and maximize the cost-benefit ratio of trial execution. Design and conduct of phase 3 trials should be coordinated by centers with appropriate expertise in HCC.

Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge—conventional TACE. Recently, a drug-eluting bead (DC Bead®) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.

No abstract

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes.

RF ablation is superior to PEI with respect to local recurrence-free survival rates.