Radiation treatment prolonged liver cancer patients' lives, U-M study finds

11/22/05

Focused radiation combined with chemotherapy makes headway against one of the most deadly types of cancer

ANN ARBOR, Mich. - Surgery is the most effective way to treat tumors that grow in the liver. But for most patients, the tumor is growing in a way that it can't be removed. And when that happens, few options remain.

Now, researchers at the University of Michigan Comprehensive Cancer Center are reporting success with a new method of attacking these cancerous tumors. Radiation is aimed precisely at the tumor - not the entire liver - and 400 times the normal amount of chemotherapy is fed directly to the liver. The combination delivers an intensive punch directly to the tumors while limiting exposure to normal tissue.

Of the 128 patients treated, median survival was 15.8 months, significantly longer than traditional survival rates for patients with these types of tumors. Results of the study appear in the Dec. 1 issue of the Journal of Clinical Oncology.

The researchers looked specifically at patients with bile duct cancer, liver cancer or colon cancer that had spread to the liver, all of whom were not candidates for surgery. Typical survival rates for these cancers are eight or nine months. In this study, liver cancer patients lived an average 15.2 months, bile duct cancer patients lived 13.3 months and colon cancer patients lived 17.2 months.

"The patients with metastatic colorectal cancer who were entered in this trial, for example, were for the most part out of chemotherapy options at the time of referral. These are patients that we estimate would have had a life expectancy of nine, maybe 12 months. They also did not have any surgical or other local treatment options. So a median survival of 17 months in such patients is quite a substantial improvement and definitely clinically relevant," says lead study author Edgar Ben-Josef, M.D., associate professor of radiation oncology at the U-M Medical School.

In the study, patients received radiation twice daily for two weeks, along with a continuous infusion of the chemotherapy drug floxuridine. The patients then had a two-week break before repeating the radiation and chemotherapy regimen for another two weeks. The chemotherapy was delivered through a catheter into the artery that directly feeds the liver.

The treatment was developed at U-M by Theodore Lawrence, M.D., Ph.D., Isadore Lampe Professor and Chair of Radiation Oncology, and William Ensminger, M.D., Ph.D., professor of internal medicine.

Traditionally, radiation therapy has not been effective against liver cancer because the liver is too sensitive to receive radiation. Instead of treating the entire liver, though, the U-M researchers theorized they could focus the radiation on only the tumor. The radiation oncologists designed a treatment that directly targets the tumor, using conformal radiation techniques that pinpoint precisely where the radiation beams go. This allows a higher dose of radiation to be used and spares as much of the normal liver tissue as possible.

As a result, less than a third of the patients in the study experienced severe complications from the treatment. The most common severe problems were upper gastrointestinal ulcers or bleeding, liver disease from the radiation and problems from the catheter.

The chemotherapy delivery takes advantage of the liver having two major blood supplies but needing only one. The tumor lives off one of the two blood supplies, and the artery feeding into the liver actually feeds the tumor's growth. With the treatment used in this study, the chemotherapy is infused directly into this artery so the drug goes directly to the tumors in the liver.

The liver is also where chemotherapy drugs are typically processed and removed from the blood supply. By targeting the drugs to the liver, very little of the drug travels throughout the body, allowing researchers to deliver a higher dose.

Most often, liver tumors originate as cancer in another part of the body and spread to the liver. Primary liver cancer, or cancer that starts in the liver, is among the most serious and deadly types of cancer. Typically, it's not discovered until an advanced stage because it causes few distinct symptoms. About 17,500 people are expected to be diagnosed with primary liver cancer or bile duct cancer this year, and 15,420 will die from it, according to the American Cancer Society.

Researchers are continuing to refine the treatment, using newer radiation techniques to deliver higher doses of radiation. Further studies are also looking at testing liver function during treatment to identify the patients who are experiencing side effects, allowing the majority of patients who can handle higher doses of radiation to receive it - which would potentially result in better tumor control for that group.

Additional study authors are Daniel Normolle, Ph.D., research assistant professor of radiation oncology; Suzette Walker, N.P., nurse practitioner; Daniel Tatro, radiation therapy dosimetrist; Randall K. Ten Haken, Ph.D., professor of radiation oncology; James Knol, M.D., associate professor of surgery; Laura Dawson, M.D., clinical assistant professor of radiation oncology; and Charlie Pan, M.D., lecturer in radiation oncology.

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