The Rise of Radioembolization

A sophisticated approach is gaining favor as a primary liver cancer treatment

Email Print

Matthew Johnson, MD, FSIR, is professor of radiology and surgery at Indiana University School of Medicine.

Liver cancer is a disease that presents clinicians and patients with significant challenges. That is true in part because untreated liver cancer patients measure their survival time in months, not years.

Treating the disease has usually been the primary responsibility of oncologists. But with the emergence of new options, such as radioembolization with TheraSphere, interventional radiologists are playing an increasingly important role in treating liver cancer.

This article outlines the most common approach that my colleagues and I at Indiana University Hospital in Indianapolis are taking to treat primary liver cancer, or hepatocellular carcinoma (HCC). Cooperation among specialties, not competition, is central to our philosophy. We emphasize a multidisciplinary approach that integrates interventional radiology with radiation, medical and surgical oncologists, hepatologists, transplant surgeons, physicists, and technologists. 

Liver Disease Increasing

At our institution we have seen a significant increase in the number of liver cancer patients, which has made our center one of the top three for liver transplants in the country. It's not surprising that we are seeing more cases, given the increasing prevalence of conditions that place people at greater risk for liver cancer, such as hepatitis, obesity, and alcoholism. For example, more than 4 million Americans have been infected with hepatitis C, according to the American Liver Foundation.

Globally, the World Health Organization estimates hepatitis C affects an estimated 3 percent of the world's population. Liver cancer is the fifth most common cancer overall and the third most deadly cancer.

By the time most liver cancers are diagnosed, they cannot be safely removed by surgery. Only an estimated 5 percent to 10 percent of diagnosed HCC is resectable, according to a 2004 paper by J.M. Llovet, MD, published in Current Treatment Options for Gastroenterology.

For unresectable HCC, transarterial chemoembolization is the long-established standard of care. That procedure involves injecting chemotherapy agents, along with an embolic agent that helps retain the chemotherapy in the diseased organ, into the hepatic artery or arteries that feed the cancer. Chemoembolization has been demonstrated to afford increased life expectancy for HCC patients. But patients don't always tolerate chemoembolization well. The risk of complications, including frequent nausea and vomiting, makes it an inpatient procedure.

Finding Alternatives

In the search for alternatives, radioembolization with Y-90 glass microspheres has emerged as an increasingly popular option. At our facility, we prefer this approach instead of chemoembolization for patients with unresectable HCC. Patients typically tolerate radioembolization well, and the rate and extent of complications are low enough to make it an outpatient procedure.

Though it is regarded as having low toxicity, the treatment has some common side effects, including mild to moderate fatigue for a week or two in most patients, and abdominal pain and nausea in under 25 percent of patients. Other facilities have reported occasional loss of appetite, but that is uncommon. As with any radiation treatment, patients should expect to be tired afterward. Some experts have even likened the side effects to the common flu.

We see limited postembolization syndrome with radioembolization when compared with traditional embolization procedures. It's rare that patients experience the more extreme fatigue, nausea, and vomiting usually associated with high-dose, systemic chemotherapies.

There’s a substantial advantage for patients with portal vein thrombosis (PVT), according to a paper by Laura M. Kulik, MD, et al. in the January 2008 issue of Hepatology. The PVT population comprises between 26 percent to 35 percent of HCC patients. PVT is a contraindication for most embolic therapies. TheraSphere radioembolization represents a safe, FDA-approved treatment in which therapy is delivered to patients with Institutional Review Board oversight. (TheraSphere is approved by the FDA under a humanitarian device exemption.)

Radioembolization is a potential treatment for patients where surgery, transplantation, or tumor ablation is not an option. Successful use of this treatment can downstage some patients and provide a link to additional treatment options, such as radiofrequency ablation, a transplant, and surgery.

Another study by Laura M. Kulik. MD, et al. published in the Journal of Surgical Oncology (December 2006) documents results for using TheraSphere radioembolization to downstage patients. Kulik and colleagues looked at 150 unresectable HCC patients. Depending on each patient’s status and disease progression, the treatment intent was to downstage to T2, resection or radiofrequency ablation, or bridge to transplant.

The results in the Kulik study were as follows:

• 19 of 34 (56 percent) were downstaged to T2

• 11 of 34 (32 percent) were downstaged to target lesions < 3.0 cm

• 1 patient (3 percent) was downstaged to resection

• 8 (23 percent) received orthotopic liver transplantation

• 4 of 34 (12 percent) saw their disease progress.

Details of the Procedure

Prior to the radioembolization procedure, consultation occurs within our team and with the patient about the best available treatment option. Once radioembolization is selected as the preferred treatment option, initial imaging (CT or MR), an arteriogram, and other imaging procedures are performed to assess vasculature and blood flow. To minimize non-target radioembolization outside the liver, it might be necessary to perform metal coil embolization of the gastroduodenal and gastric right artery, or other non-target arteries.

Radioembolizations are performed in the radiology suite using fluoroscopy-guided catheterization through the femoral artery. The patient remains conscious during the procedure. The catheter is guided into the branch of the hepatic artery feeding the tumors, and the glass microspheres are infused into the vasculature and migrate toward the tumors through the hepatic blood flow.

Because arterial blood flow is usually greater within the tumor, there is preferential delivery of microspheres to the tumor capillary bed, which allows targeted delivery of higher radiation doses directly to the tumor relative to the surrounding non-tumor parenchyma.

The tiny microspheres emit radiation in a small diameter of approximately 2.5 mm from each sphere. The radioisotope yttrium-90 (Y-90) has a half-life of 64.1 hours and decays to stable zirconium-90. The dosimetry, which is based on the volume of targeted liver tissue, is reproducible and comparatively simple.

Exploring Treatment Options

While radioembolization is the preferred approach to HCC at our institution, there are other options, such as the following.

• Radiofrequency ablation of the tumors. This therapy may be the best choice for patients who have three or fewer tumors 3 cm in diameter or smaller and who are not candidates for transplantation.

• Transarterial chemoembolization. We employ this option only in the uncommon cases where radioembolization is unsuitable for the patient.

• Stereotactic body radiotherapy. A sophisticated form of external beam radiation known as stereotactic body radiotherapy is often appropriate for single tumors less than 6 cm in diameter.

• Bland embolization. Bland embolization is used only if a patient is scheduled for transplant within the next month.

Recent Research Findings

As interventional radiologists begin performing more radioembolizations, extensive data are emerging about the treatment. For example, Riad Salem, MD, professor of radiology, medicine and surgery at Northwestern University in Evanston, Ill., led a study that appeared in the journal Gastroenterology (January 2010). Researchers assessed clinical outcomes using TheraSphere in 291 patients with HCC. Their findings are among the first to examine radioembolization treatment with a large cohort of patients at stages of disease progression.

Among the strengths of this research is the guidance it offers about what particular patient type can benefit from this treatment. They found the best candidates are patients with HCC at Child-Pugh A stage (less severe), with or without portal vein thrombosis. “These data can be used,” Salem and colleagues wrote, “to design future Y-90 trials and to describe Y-90 as a potential treatment option for patients with HCC.”

Indeed, as these and other studies have indicated, optimal results for radioembolization are directly related to patient selection. There have been recent, favorable developments in terms of insurance coverage. While the treatment has been eligible for Medicare reimbursement and has been covered by many insurers, some larger insurers have resisted. However, two of the nation’s largest health insurance companies recently decided to fully cover radioembolization when it is medically necessary.

A multidisciplinary approach to treating HCC, especially when using radioembolization, is one of the keys. Interventional radiologists outside large institutions can successfully offer this option. But regardless of the practice setting, it’s worth taking the time and effort to achieve the structured, cooperative amalgamation of expertise that various specialties can bring to the treatment process, and those skills will ultimately benefit the patient.

–Matthew Johnson, MD, FSIR, is professor of radiology and surgery at Indiana University School of Medicine in Indianapolis. Direct comments and questions to editorial@rt-image.com.