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Long-Term, Low-Dose, Intermittent Interferon After Curative Radiofrequency Ablation May Prevent Recurrence of Hepatocellular Carcinoma: Presented at UEGW

By Chris Berrie

PRAGUE, CZECH REPUBLIC -- September 29, 2004 -- Low-dose, long-term interferon (IFN) therapy after curative radiofrequency ablation (RFA) is able to counteract the high recurrence rate of hepatitis-C-related hepatocellular carcinoma (HCC), according to a study presented here September 27th at the 12th United European Gastroenterology Week.

Masatoshi Kudo, MD, professor, gastroenterology and hepatology, Kinki University School of Medicine, Osaka-Sayama, Japan, presented these results from a retrospective, matched-case control study.

He said that among 137 out of 980 initial curative RFA treatments for HCC in his clinic between 1999 and 2004, the 5-year cumulative survival rate after RFA was 66.3%. However, this was formed from a local recurrence rate of 6.2%, compared with a much greater intrahepatic distant recurrence rate of 85.6%, he added.

"Therefore, the prognosis of HCC after curative treatment by RFA is mainly determined by intrahepatic distant recurrence rather than local recurrence, and in order to improve prognosis, secondary protection for HCC recurrence is mandatory," Dr. Kudo said. Therefore, they investigated the potential for IFN therapy to prevent recurrence and eventually improve the prognosis of patients with hepatitis-C-related HCC after complete curative RFA therapy.

In the study, 35 patients who received initial curative RFA therapy and had small HCC tumours (< 3 cm) and fewer than 3 nodules received the IFN therapy, which involved 3 MIU IFNalpha-2b twice weekly for a median observation period of 3.5 years (range, 0.6-5.1 years). The control group was made up of 35 HCC patients who received curative RFA therapy but did not receive IFN therapy were matched by age, platelet counts, and size of nodules (median observation, 3.2 years; range, 0.6 to 4.5). There were no statistically significant differences between these two groups in liver function, tumour morphology and tumour markers.

The IFN group had a significantly longer period to the first recurrence after RFA therapy compared with control patients (3.4 years vs. 1.4 years, P =.022, respectively). However, while the IFN group's cumulative rate of first recurrence after RFA was significantly lower initially (P =.0207), over the 5-year observation period it reached the same maximum as the control group (81%). The 5-year cumulative rate of second recurrence was much better for the IFN patients (31% vs. 89%, P =.035), and the rates of third recurrence were 0% and 70%, respectively.

Dr. Kudo also said the 5-year cumulative survival rates with IFN were 100% and 72%, respectively (P =.08) and the rates of disease control at 5 years were 100% and 52%, respectively (P =.04). He also stressed that a breakdown of the recurrence patterns in the two groups illustrated further the beneficial effects of IFN.

Finally, an analysis using the Cox proportional hazard model revealed IFN therapy to be an independent risk factor for recurrence (risk ratio, 4.395; P =.0172), as were the size (risk ratio, 16.059; P =.0198) and number of the nodules (risk ratio, 12.045; P =.0004).

These data demonstrate that long-term, low-dose, intermittent IFN delays the first recurrence and inhibits the second and third, allowing for repeated curative RFA and hence improved disease-free and overall survival, Dr. Kudo said, adding that these beneficial actions of IFN potentially arise from its direct growth inhibitory action on hepatic metastases.


[Presentation title: "Low-Dose, Long-Term Interferon Therapy Delays Clinical Recurrence After Curative Radiofrequency Ablation in Patients With Hepatitis-C-Related Hepatocellular Carcinoma. Abstract OP-G-86." Abstract 546]

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