Nov./Dec. | 2009
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From Bench to Bedside:
Local Focus
Researchers strive for local control of pancreatic cancer

Earlier this decade, researchers at the University of Michigan Comprehensive Cancer Center were trying to use a new type of chemotherapy, gemcitabine, in combination with radiation therapy to improve the treatment of pancreatic cancer.

The idea didn’t get much traction. Like most studies involving pancreatic cancer, the dismal survival rates did not improve much.

But from there, researchers used the same drug and began to tinker with the way they delivered the radiation, using a cutting-edge technique called intensity-modulated radiation therapy, or IMRT.

Local FocusU-M researchers work to achieve higher doses of radiation to treat pancreatic cancer. Now, researchers are in the middle of a Phase I/II trial of this approach that is generating very promising early results – survival times nearly double what’s expected. The findings also potentially show a whole new way to understand why pancreatic cancer is so deadly.

The Concept
Intensity-modulated radiation therapy uses a cluster of tiny beamlets to deliver radiation very precisely. Each beamlet carries a different intensity of radiation. This allows the beams to wrap carefully around a tumor with a precision that limits the radiation exposure to normal tissue.

The pancreas is a classical example of why such tissue-sparing techniques are crucial. It’s wrapped around multiple sensitive organs such as the stomach, duodenum, small bowel, liver, kidneys and spinal cord. The radiation needs to hit the pancreas, but if too much hits these other structures, it can cause severe side effects.

The other advantage to IMRT is it allows oncologists to deliver higher doses of radiation to the tumor. The U-M researchers sought to determine the highest radiation dose that can be delivered safely, and whether that – combined with the chemotherapy drug gemcitabine – would improve survival.

“When we started this work, we thought physicians did not use high enough doses of radiation in pancreatic cancer. Historically, we have compromised on the dose to spare all these other organs. But with this new technique, we found we could achieve higher doses while still sparing the other organs,” says Edgar Ben-Josef, M.D., professor of radiation oncology.

Increasing Radiation Doses
Previously, with conventional techniques, the maximum radiation dose that could be delivered with full-dose gemcitabine was about 36 Gy. A gray, or Gy, is a unit of absorbed radiation dose. Through this study, researchers have determined a dose between 55 Gy and 57.5 Gy can be given safely and be well tolerated by patients.

Researchers found that while the radiation dose to the tumor increased, the radiation to the nearby organs decreased, compared to conventional methods.

The researchers have presented data on the first 27 patients in the study, finding that only one patient’s cancer advanced within the pancreas. Typically, at least one-third of patients would have had this local progression. Progression to metastatic disease outside the pancreas, however, happened at a similar.

Most impressive is that survival doubled. Patients lived a median of 23 months, compared to the standard 10 to 13 months -- a number that has barely budged in more than 20 years.

Treatment Tomorrow
Ben-Josef believes the improved local cancer control is extending survival. A study published earlier this year from another team of researchers found that metastatic disease was not the cause of death in about 30 percent of pancreatic cancer patients. Rather, these patients died from local issues such as perforation or bleeding in the nearby small bowel or blockage of the bile duct that causes a lethal infection.

“There’s a paradigm shift here,” Ben-Josef says. “With this treatment, we control the disease locally much better than before and patients continue to live despite some spread of cancer to their liver or lungs.”

The ongoing trial has accrued approximately 40 of the 50 participants needed. The researchers are also writing a new multi-site Phase II trial to verify their results.

Written by Nicole Fawcett

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