Local Control With Hepatic Chemoembolization/RFA

SEATTLE—The combination of hepatic chemoembolization and radiofrequency ablation (RFA) achieves local control in 83% of patients with hepatic malignancies, Mikhail C.S.S. Higgins, a medical student at Wake Forest University School of Medicine, reported at the 32nd Annual Meeting of the Society of Interventional Radiology (abstract 124). Mr. Higgins conducted the research at the Hospital of the University of Pennsylvania along with Michael C. Soulen, MD, professor of radiology.

Some patients with hepatic malignancies who are ineligible for resection can undergo RFA, which induces coagulative necrosis in tumors. "The problem with radiofrequency ablation is that there is a cooling effect from the blood flow that is supplied to the tumor," Mr. Higgins said, leading to a high local failure rate in larger tumors.

Chemoembolization also induces necrosis but interrupts arterial blood flow to liver tumors as well. "In a number of European studies, the investigators combined embolization with thermal ablation and showed successful treatment in controlling progression in hepatocellular carcinomas up to 8 or 9 cm," Mr. Higgins said. "So we wanted to build on this premise by adding embolization to RFA to see if we could diminish the dissipation of heat effect that we tend to see in using RFA as a unimodal treatment."

In the retrospective study, the investigators analyzed outcomes in 44 patients treated with chemoembolization followed by RFA between 1998 and 2006. They had 53 hepatic tumors measuring greater than 2 cm in diameter. Of these 53 tumors, 37 were hepatocellular carcinomas and 16 were hepatic metastases. The mean tumor size was 4.4 cm (range, 2.2 to 9 cm).

Patients underwent chemoembolization with cisplatin, Adriamycin (doxorubicin), and mitomycin (CAM); ethiodol; and polyvinyl alcohol (PVA), followed the next day by RFA with probes of various sizes. In the seven patients with bilobar disease, the tumor in the second lobe was treated 4 to 6 weeks after that in the first.

Laboratory evaluation and imaging were performed at 1 month and then every 3 months thereafter, and patients were followed until transplantation or death. The median follow-up was 10 months (range, 1 to 36 months).

The combination treatment had a technical success rate of 98%, Mr. Higgins reported. Five patients had major complications: abscess formation with bilocutaneous fistula (one patient), grade 2 fever from transient bacteremia (three patients), and grade 2 fever from spontaneous bacterial peritonitis (one patient). One patient had a minor complication, a large groin hematoma not requiring any intervention.

Tumor marker levels, evaluable in 21 patients, decreased in 11 patients, remained stable in 5, and increased in 5, Mr. Higgins noted. For 44 of the 53 tumors (83%) in 35 patients, there was no local recurrence (no contrast within the tumor or nodular enhancement) during a follow-up ranging from 1 to 14 months. However, the 4-month rate of freedom from local recurrence was significantly higher in patients with hepatocellular carcinoma than in patients with hepatic metastases (88% vs 35%).

Among the 35 patients without local recurrence, 21 (60%) had a progression at another site (distant failure), and in the majority of cases, this progression was intrahepatic progression at a new site, Mr. Higgins said. The rate of distant failure was also somewhat higher in patients with metastatic disease (67%) than in patients with hepatocellular carcinoma (41%). Twelve patients in the study group went on to transplantation.

"Overall 1-year survival from administration of combination therapy was 55% in individuals with hepatocellular carcinoma, with a median of about 16 months, vs 25% for individuals with liver metastases, with a median of 9 months," Mr. Higgins said.

Study Limitations

One of the study's limitations, Mr. Higgins noted, was that the patients with liver metastases had a wide variety of primary tumors. "Obviously, each of these tumors has various pathologies and various responses to treatment, and the outcome is going to be different, which makes it difficult to generalize these results," he said. In terms of survival as well as local control and progression, he said, "there is greater palliation rendered to individuals who have hepatocellular carcinomas vs those with liver metastases."

Despite the local control that was achieved, he said, "in the absence of transplant, obviously limited efficacy is achieved in terms of preventing progression at new sites, and this remains a therapeutic challenge."