Additional Application of Interferon-Apha After Complete Destruction (CD) of Hepatocellular Carcinoma (HCC): Influence on Local Tumor Progression (LTP)
Background: Interferon-alpha blocks cell cycle in HCC cultures, modulates proto-oncogen expression, induces apoptosis, activates NK-cells, inhibits neoangiogenesis and suppresses hepatoma proliferation in proportion to the applied dose.
Aim: To estimate the role of Interferon-alpha in the prevention of LTP after accomplished CD of HCC.
Methods: Ex-vivo hepatoma cell lines were created and proliferation was suppressed by Interferon-alpha at 72 hours of culture, thus giving rationale for local administration of the drug. 46 patients with 48 HCC (size 3.5-14.5cm) were treated with US-guided percutaneous single-session large-amount (30-138 ml) ethanol instillation (Shot-PEI) in a 7-year period. The achieved destruction was assessed using contrast-enhanced US/CT and biopsy. Interferon-alpha was injected intra- and perilesionally in 12 patients with fulfilled CD, for 1-4 months 1-3x weekly. Patients were followed-up for 6-43 months. The results were compared to a control group treated with Shot-PEI alone. LTP was retreated when feasible.
Results: LTP developed in 5 cases treated with Interferon-alpha (41.7%). Time to LTP ranged 11-34 months. In 1 patient LTP occurred twice and in 1 case – thrice. In the control group LTP rate was 44.4% (n. s.), with mild difference concerning time to LTP, and similar cumulative 36-months survival.
Conclusion: The success of the first ablation predetermines favourable outcome. The applied schedule of additional treatment with Interferon-alpha fails to exhibit clear advantage in terms of LTP. Further studies are needed to elucidate its role in the prevention of LTP, including identification of the subgroup of patients/tumors-responders to Interferon-alpha and improvement of the dose regimen.