April 2011

Liver Tumor Interventions — ISET Symposium on Interventional Oncology Examines Catheter-Based Treatments for Hepatocellular Carcinoma
By Beth W. Orenstein
Radiology Today
Vol. 12 No. 4 P. 22

In developing countries, liver cancer is the third leading cause of cancer deaths. In the United States, it is the eighth leading cause.

However, in contrast to most other major forms of cancer, liver cancer is on the rise in the United States. According to a study by the Centers for Disease Control and Prevention (CDC) released in May 2010, the rates of hepatocellular carcinoma (HCC), the most common form of liver cancer, increased from 2.7 cases per 100,000 people in 2001 to 3.2 cases per 100,000 in 2006—an average annual increase of 3.5%.

It takes decades of being infected with hepatitis before a person develops cancer. Yet scientists believe that untreated chronic viral hepatitis infections are to blame for the increase in liver cancer cases. This increase is despite the availability of a vaccine against hepatitis B that is routinely given to children; adults, for the most part, aren’t protected. (Hepatitis C was only discovered in 1990, and there is no public vaccine for it.) Most of the 4.4 million Americans living with chronic hepatitis do not know they are infected, and about 80,000 new infections occur each year.

In addition to primary liver cancer, according to the American Cancer Society, each year another 100,000 people develop metastatic liver cancer from cancer that originated elsewhere in the body.

The good news is that minimally invasive interventional oncology treatments can treat a larger number of primary and metastatic liver cancers, and interventional radiologists have been improving their techniques. At the Symposium on Clinical Interventional Oncology, held in collaboration with the International Symposium on Endovascular Therapy (ISET), in January, Charles Nutting, DO, FSIR, an interventional radiologist at the Swedish Medical Center in Denver, reported on the success of bathing tumor-ridden livers in chemotherapy drugs. He presented results from a multicenter randomized phase 3 trial that showed minimally invasive chemosaturation delivers high doses of chemotherapy into the liver to more effectively battle tumors while limiting toxicity to the rest of the body.

“The minimally invasive method isolates the drug so that it’s contained within the liver, where tumors receive up to 100 times the dose they would get through systemic chemotherapy,” Nutting says. The trial involved patients with cutaneous and ocular melanoma that had spread to the liver. However, he says, “This minimally invasive therapy could eventually be used to treat other liver cancers when the options are limited.”

Patients with cutaneous and ocular melanoma have a fairly grim prognosis once it has metastasized to the liver, Nutting says. Patients with cutaneous and ocular melanoma tend to be young, and about one-half develop liver metastases and survive only about four to five months. “Our efforts have been concentrating on stabilizing the liver for as long as possible,” Nutting says.

Survival Benefit
In the trial, patients with melanoma that had spread to the liver who underwent percutaneous hepatic perfusion (PHP) survived four times longer before the disease progressed compared with patients who did not receive the treatment, according to the results. The study included 93 patients; 44 received PHP and 49 received standard treatment (typically systemic chemotherapy). In the former group, 27 began receiving PHP when their disease progressed. Patients in the PHP group averaged 185 days before the disease progressed compared with 46 days for patients who did not receive PHP. Those in the PHP group benefited from an average of 245 days without progression of the cancer in the liver compared with 49 days for those in the standard treatment group—a fivefold increase for the PHP group.

Nutting explained that PHP, which takes about 90 minutes to perform, involves delivering chemotherapy via an arterial catheter threaded through the blood vessels to the liver. Two balloons are inflated in the vena cava, above and below the liver, to isolate the chemotherapy. This chemotherapy-saturated blood is then cleansed by a series of filters and returned to the body.

PHP allows the entire liver to be treated, which is beneficial for patients with more than one tumor. In standard chemotherapy, the drug travels throughout the entire circulatory system, and doses must be minimized to prevent damage to healthy tissues. Localized chemotherapy involves delivering treatment to specific tumors, enabling the use of higher doses. The method is more challenging when the patient has multiple tumors, Nutting says.

The procedure is well within the scope of practice for interventional radiologists who specialize in liver-directed therapies, according to Nutting. “You need guidance for the first couple of procedures, but it’s a skill set that you can become very comfortable with. We have done about 10 in our practice,” he says.

The liver is very well suited for this type of chemotherapy, Nutting says, because of its dual blood supply. However, “It’s a platform technology that may prove itself in treating other types of cancers,” he adds.

FDA approval of PHP is pending and could come within a year, Nutting says, noting that the FDA has requested some additional safety data.

“I think it is exciting technology and one more example of how we can get therapy to an organ with minimal side effects,” he says.

Transcatheter Chemoembolization
At the symposium, interventional radiologists also discussed using a combination of transcatheter chemoembolization and tumor ablation to treat primary liver tumors that cannot be surgically removed because of their size or location. Chemoembolization focuses chemotherapy treatment directly on the tumor so that little, if any, healthy tissue is affected by the therapy. Tumor ablation uses heat, cold, radio frequencies, or other substances such as alcohol to help shrink the tumors.

Riccardo Lencioni, MD, an interventional radiologist from Cisanello University Hospital in Pisa, Italy, says that in June 2008, his team published the first clinical experience with the combination of radio-frequency ablation (RFA) and drug-eluting beads for chemoembolization in the Journal of Hepatology. The study showed that the combination of therapies greatly improved the ability to eradicate liver tumors compared with RFA alone.

“We successfully treated encapsulated noninvasive tumors as large as 7 cm in diameter that were refractory to a standard RFA treatment,” he says. Lencioni notes that 7 cm was the upper limit in the study “and probably still is.” The combination techniques have also enabled interventional radiologists to treat more liver cancers, he adds.

During one trip to the interventional radiology suite, Lencioni prefers performing RFA first immediately followed by the chemoembolization with drug-eluting beads. “If you do the RFA first in a large tumor mass, you kill the center of the tumor and so you’re able to administer a more concentrated dose of drug-eluting beads to the remaining tumor. If you killed 90% of the tumor with RFA, it means the drug you are administering is concentrated in just 10% of the tumor tissue,” he explains.

In the study, Lencioni’s team performed the two procedures separately over a 24-hour period. “The limitation of this combined approach is that two different interventional procedures need to be carried out on the patient. While this proved to be safe in properly selected candidates, it clearly adds to the complexity of the treatment and the overall costs,” he says.

There is debate among interventional radiology oncologists whether the two should be performed simultaneously or on separate days. Robert K. Ryu, MD, an interventional radiologist at Northwestern University in Chicago, says his preference is to perform the second procedure the next day. “The idea is to create ischemia to increase the ablation zone size, and that’s probably the highest immediately after the embolization,” he says.

Ryu says the combination of treatments has definitely expanded the number of patients who are candidates for ablative treatments. “I think most practitioners are pretty comfortable with ablating small lesions. The combination approach may be a way to expand the size criteria of lesions that would become ablatable,” he says.

Transplant Criteria
The only way liver cancer patients have a significant chance of long-term survival, Ryu says, is by undergoing a liver transplant. “I’m talking about patients with hepatic carcinoma because they will typically also have underlying cirrhosis. If the tumor doesn’t kill them, then liver failure will,” he notes.

Ryu says his rationale for treating patients with a combination of RFA and chemoembolization is to keep them within the transplant criteria. “Once you get to a certain size tumor, you are technically outside the transplant criteria. We try to control the tumors and keep them within transplant criteria with RFA and chemoembolization or other methods,” he explains. “Also, if the tumors respond to treatment without evidence of progression or new tumor development, then you are likely to have a lower incidence of tumor recurrence after transplantation.”

 Shaun Samuels, MD, an interventional radiologist at the Baptist Cardiac & Vascular Institute in Miami and head of the symposium, says more research needs to be done to determine which ablative techniques are best for treating particular cancers, yet this is unlikely to happen because both RFA and cryoablation for solid organ tumors have FDA approval. “So there’s not much impetus to sponsor such head-to-head trials between competing ablative technologies,” he says.

Is radioembolization better than chemoembolization? Each camp has fervent adherents, Samuels says. Should drug-eluting beads replace embolization? That question, too, needs further study, he says. Lencioni also has a preference for drug-eluting beads over conventional chemoembolization and defended his position at a debate at the symposium.

Whether single or combined treatments are best is far from settled, Samuels says. “Right now, we’re talking about the combination therapy as if it’s a done deal,” he says. “Obviously, we believe that transcatheter chemoembolization and ablation work on their own, and there is a reasonable amount of evidence to suggest that they do. A lot depends on exactly what type of tumor we’re talking about in the liver. But many people believe there is improvement to be had by combining the two therapies. We must remember that the end point is prolonging patient survival and improving the quality of life during that survival.”

— Beth W. Orenstein is a freelance medical writer based in Northampton, Pa. She is a frequent contributor to Radiology Today.