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Believing in Hope:

U-M researchers work to shed light on the grim world of pancreatic cancer, con't.

Up to 30% of the cancer stem cells found in some patient tumors analyzed in Simeones research were positive for CD44 and c-Met and were "incredibly aggressive," according to Simeone. "Tumors with lower populations of CD44 and c-Met were much less aggressive and don't seem to metastasize in mice." These cells may be key to defining a cancer stem cell "signature" in pancreatic cancer.

Limited treatment options

Theodore Lawrence
photo credit: Austin Thomason, Michigan Photography

In 15 to 20% of patients diagnosed with pancreatic cancer, surgery is an option, because the tumor is still confined within the pancreas. But the procedure is complicated by the tumors tendency to surround major blood vessels and nearby organs in the abdomen. Removing the tumor without damaging a major artery or vein requires the highest levels of experience and skill and sometimes is simply impossible. Giving patients chemotherapy and radiation prior to surgery can help shrink the tumor and make it easier to remove surgically. And if the tumor cannot be removed with surgery, chemoradiation is the only possible treatment option.

One of the drugs most often used to treat pancreatic cancer is gemcitabine. It's called a radiation sensitizer because, in addition to directly killing tumor cells, it makes tumor cells more sensitive to radiation. Determining the most effective way to combine gemcitabine with radiation has been a major focus of clinical trials conducted by U-M oncologists. U-M clinical researchers also are testing the effectiveness of combining gemcitabine with another class of drugs called checkpoint inhibitors that interfere with cells ability to repair damaged DNA.

While surgery and chemotherapy are widely accepted as treatments for pancreatic cancer, the effectiveness of radiation therapy is more controversial, especially for patients after surgery. A clinical trial in Europe of patients who had chemoradiation therapy after surgical resection of their tumor found no benefit. But a trial in the United States found that patients lived longer if they received post-surgical chemoradiation. A new clinical trial involving pancreatic cancer patients from many medical centers in Europe and the U.S., including the U-M Health System, will attempt to answer the question more definitively.

Theodore S. Lawrence, M.D., Ph.D., the Isadore Lampe Collegiate Professor of Radiation Oncology and chair of the department, believes the results of the new trial will prove that radiation is an important part of the treatment protocol.

"In my opinion, the evidence is incontrovertible that, for patients who have a tumor that cant be removed, adding radiation to chemotherapy is better than using chemotherapy alone," says Lawrence. But he emphasizes that not just any type of radiation will do.

Lawrence says U-M researchers have perfected the use, in pancreatic cancer, of an advanced technique called intensity-modulated radiation therapy (IMRT). It allows radiation oncologists to deliver the most intense dose of radiation to the tumor, while minimizing radiation to surrounding tissue and organs especially the duodenum of the small intestine, which surrounds the pancreas.

"With IMRT technology, we can curve the high-dose region, so it hits the tumor and just skims the duodenum," says Lawrence. "Minimizing radiation damage to the duodenum helps reduce side effects from treatment."

Even though treatment options are limited, current outcomes arent good, and a cure remains a distant goal, those who work with and on behalf of pancreatic cancer patients are undaunted. "I'm a big believer in hope," says Simeone. "I always talk to my patients about the various therapies we have to buy them time."

 

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This article first appeared in the Spring, 2012 issue of Medicine at Michigan.