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Progress, Fall 2004

Clinical Focus: Treating Cancer in the Liver

When cancer invades this curious organ, it takes a remarkable team effort to prevail

Dave Smethurst credits the insight and experience of a local physician with detecting his rare cancer, and a team of U-M physicians and scientists he calls "brilliant thinkers, amazing explainers and truly compassionate human beings" with saving his life.

In the Fall of 1999, Smethurst, a retired high school principal from Gaylord, Michigan, began to display symptoms causing his doctor to suspect a growth in the intestinal tract called a carcinoid tumor. This unusual cancer secretes hormones that cause additional tumors to form in other sites, including the liver. Smethurst's doctor referred him to the U-M Comprehensive Cancer Center to confirm the diagnosis and determine the best course of treatment.

"Of course, when you first come through the door, you're scared to death," recalls Smethurst. "But after meeting the U-M team that would be caring for me, and learning as much about my kind of cancer as a layman could, I knew I was in one of the best places in the world for a cancer patient. I was still scared, but much less so. I was ready."

Smethurst's first contact at Michigan was John Del Valle,M.D., professor and senior associate chair of medicine in the Department of Internal Medicine's Division of Gastroenterology. A carcinoid specialist, Del Valle referred the case to Theodore Lawrence,M.D., Ph.D., Isadore Lampe Professor and chairman of the Department of Radiation Oncology, who, along with William Ensminger,M.D., Ph.D., also a professor in the Department of Internal Medicine and director of the Cancer Pharmacology Program at the U-M Comprehensive Cancer Center, were testing a unique treatment that held promise for Smethurst.

Carcinoid cancer can start as a small tumor on the intestine. However, the tumor can metastasize to other organs, primarily the liver. Surgery can often remove the initial tumor and many or all of the subsequent tumors on the liver -- and that marvelous organ is capable of regenerating itself in the process. But some liver tumors cannot be removed surgically, either because of their large size or their location. That leaves few treatment options. "I had about a dozen tumors, and most were surgically removed," explains Smethurst. "But three on my liver couldn'Tt be, which is why I was a candidate for this remarkable trial led by people right here at Michigan."

Two therapies with the power of three

To understand the U-M team's unique approach, it's important to first appreciate the unusual nature of the liver itself, and how its function can be disrupted by the presence of cancer. Unlike most organs, which receive blood from arteries, the liver gets most of its blood from veins. As Lawrence explains, "a normal liver takes and processes venous blood from the intestines during digestion. About 75 percent of the blood to a healthy liver comes from a vein and 25 percent comes from an artery. When a tumor grows in the liver, that percentage can be reversed. That's because tumors have figured out ways to get arteries to grow into them."

Mindful of this phenomenon, Ensminger pioneered a method of delivering chemotherapy directly into the arteries that feed liver tumors.The chemotherapy goes right to the tumor, and the normal liver receives relatively little of it. "Since he uses the same artery that the tumor uses for its own purposes -- in effect he's turned that artery into the tumor's Achilles heel," says Lawrence.

Working with Ensminger, Lawrence's lab showed that radiation therapy could be synergistic with the chemotherapy. "It was as though the chemotherapy counted as one and the radiation counted as one, but together they provided the benefit of three." Lawrence's team worked to refine radiation treatment planning, moving from the previous method of treating the whole liver to a more sophisticated, targeted system. The U-M radiation oncology team pioneered an approach that, as Lawrence describes it, "treats the process as surgery without a knife."

Using computer technology developed by U-M physicists, they were able to divide the liver up into thousands of boxes called volume elements, calculate the dose of radiation to administer to each element, and combine this information with the patient's clinical response to develop a mathematical equation that estimates the highest dose of radiation that can be safely given. This allows the safe delivery of over twice the amount of radiation to liver tumors than was previously possible, with significantly less radiation delivered to surrounding healthy tissue.

The treatment -- and the outcome

Taking part in the trial was challenging for Smethurst and his family. "About two months after surgery, I returned to Ann Arbor for two weeks of the chemotherapy/ radiation combination. Chemo was administered around the clock the entire two weeks, and I received radiation twice a day, so it was pretty exhausting," remembers Smethurst. He returned home for two weeks, then it was back to U-M to repeat the two-week cycle again, followed by another twoweek hiatus at home, then a third visit to U-M for a cycle of radiation. "Actually, I was pretty lucky. Since the chemo drugs were injected directly into my liver, they didn't travel through my whole body, so I missed many of their side effects."

As for the radiation component of the trial, Smethurst was impressed by the sophistication of the treatment planning. "They used computer technology to design a 'virtual reality me.' Then they practiced on the computer to find the best route to administer my treatment." Lawrence notes that the concept of judging the dose of radiation to administer based on the volume of the organ represents a significant breakthrough in treatment planning, combining higher dosing with more precision. "For patients receiving these higher doses, we prolong survival rates by a factor of three to four, and we're still pushing the envelope on that." Lawrence adds that a clinical trial based on this approach is now underway to treat lung tumors, using the same radiation concept in combination with different chemotherapy.

Now a five-year survivor, Smethurst spends time with newly diagnosed cancer patients near his home, stressing the importance of empowering yourself with information and playing an active role in your own treatment. At 57, he also serves as a role model for his peers that cancer is survivable. "People of my generation grew up hearing the word 'cancer' and automatically assuming there's no hope. That's just not the case anymore. When people see me they say, 'you look fine.' That's my message."

Several major U.S. cancer centers are now beginning to employ this technique, but none with the regularity of the U-M Cancer Center, which continues to draw patients like Dave Smethurst from around the world. The results of this trial reinforce Michigan's dedication to offering cuttingedge care for patients with unresectable liver tumors.

To learn more about the treatment of cancer in the liver, call the U-M Cancer Center's toll free Cancer AnswerLine™ at 800-865-1125.

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