“We’ll get a much better idea of how RFA works as a result of this study. If the results are promising, it will set the stage for future studies.” 

- Gerald D. Dodd III, M.D.

A large multicenter trial launched last December will gather data on the effectiveness of radiofrequency ablation (RFA) in hepatocellular carcinoma, the most common type of liver cancer.

Organized by the American College of Radiology Imaging Network, the phase II trial, ACRIN 6673, will enroll 120 patients at multiple sites.

When liver tumors are inoperable or surgery would be risky, patients and their physicians have few good options. That’s why RFA, with its ability to destroy tumors with minimal side effects, has attracted so much interest among oncologists.

In fact, RFA appears to now be the de facto standard of care for patients with inoperable, localized hepatocellular carcinoma, said Gerald D. Dodd III, M.D., professor and chair of the Department of Radiology at the University of Texas Health Science
Center at San Antonio. First introduced about 15 years ago, the procedure, which uses percutaneous applicators to heat tumor cells to over 100° C, has spread rapidly.

However, hard evidence on the efficacy of RFA so far is limited. Practice has raced ahead of the clinical trials, which up to now have included primarily small, single-institution studies, said Dr. Dodd, also chair of the RSNA Scientific Program Committee.

Learning How RFA Works

The trial will collect other much needed data, Dr. Dodd said, such as the number of RFA treatments associated with 18-month control rates, tumor recurrence rates, the size of tumors associated with the 18-month control rate and the development of tumors outside the liver.

“We’ll get a much better idea of how RFA works as a result of this study,” Dr. Dodd said. “If the results are promising, it will set the stage for future studies.”

Institutions Still Sought

The trial is expected to take place at multiple sites, including major cancer centers such as those at UCLA, the Mayo Clinic in Rochester, Minn., Brown University and Wake Forest University. Several other sites are pending, according to Donna Hartfeil, R.N., B.S.N., project manager for the trial.

Dr. Dodd noted that the trial is open to other institutions. An institution is eligible if the radiologist who will be performing the procedure has previously treated at least 15 liver tumors with RFA, including at least five with the Valleylab/Radionics device being used in the trial. Each site must have a helical CT scanner with power injector and must engage a pathologist who will be responsible for sending slides to a central pathologist for review. Sites are expected to enroll, on average, one participant per month.

Patients are eligible for the trial if they have cirrhosis and small tumors confined to the liver—a single tumor larger than 3 cm and up to 5 cm in diameter or up to three tumors that are cm or less in diameter. Among other criteria, patients must have had no prior therapy and cannot be candidates for surgery. Patients will be stratified based on severity of disease into three groups, with 40 in each group.

RFA the “Frontrunner” in Ablation Treatment

Liver cancer now kills about 15,000 people in the United States annually, according to the American Cancer Society. About 17,000 Americans are diagnosed with the disease each year, and the incidence is rising, largely because of the increase in chronic hepatitis C infections. The overall five-year relative survival rate is only about 7 percent.

While surgery is the preferred treatment for localized disease, fewer than 30 percent of patients having surgery are able to have their cancer completely removed. Moreover, surgery is not possible for many patients for a variety of reasons, including the location of the tumors in the liver and concomitant medical conditions, such as cirrhosis.

RFA is relatively new, dating back only to about 1990 when the first studies were conducted in animals. Its rapid spread was evident at RSNA 2005, Dr. Dodd noted, with more than 300 abstracts focused on the procedure. A fact sheet for staff physicians at the National Institutes of Health states that RFA is “currently the frontrunner among the many choices for local tissue ablation” and that it “may be better than other ablative techniques because it is fast, easy, predictable, safe and relatively cheap.”

In addition to RFA, nonsurgical treatments for tumors confined to the liver include cryotherapy, percutaneous ethanol injection, chemoembolization or chemotherapy applied directly to the liver. These treatments, however, also have little hard clinical data on their effectiveness. Systemic chemotherapy has not proved effective in most cases and the usefulness of radiotherapy is limited because of the liver’s susceptibility to damage from radiation and liver motion secondary to respiration.

If ACRIN’s phase II trial results are promising, the next step could be a randomized trial, Dr. Dodd said. While it is much too early to know how that trial would be designed, one possibility would be to compare RFA to one of the other non-surgical treatments, he said.

The ACRIN 6673 Protocol-Specific Application can be found online at www.acrin.org/6673_protocol.html. For more information on participating in the trial, contact Donna Hartfeil, R.N., B.S.N., at dhartfeil@phila.acr.org.


Illustration of how radiofrequency ablation (RFA) is administered to a hepatoma. The procedure uses percutaneous applicators to heat tumor cells to over 100° C.

Hepatoma Pre Ablation: Image of a hepatoma before RFA is administered.	Hepatoma Post Ablation: Image of the same hepatoma immediately after RFA treatment.