Backman

Vadim Backman

 

Photons

Researchers can look at how light bounces off human tissue to detect subtle changes potentially caused by cancer. The spectral image that results is like a fingerprint for disease.
(Illustrations by Zina Deretsky and Nicolle Rager Fuller, National Science Foundation)

 

Pancreas

Pancreas Illustration

Shining a light on pancreatic cancer

Pancreatic cancer is a silent killer, difficult to detect and difficult to treat. It rarely causes symptoms until it’s too late, and only 5 percent of those diagnosed with it live beyond five years — and most die within the first two. It killed 33,000 Americans last year alone and was the cause of death for Dizzy Gillespie, Count Basie, Billy Carter, M. Scott Peck, Joseph Cardinal Bernadin, and Luciano Pavarotti. Though pancreatic cancer is the 10th most prevalent cancer among American men and women, it is the fourth leading cause of cancer deaths.

One major reason for the grim survival rates is the lack of an effective diagnostic tool for early-stage pancreatic cancers. Patients don’t become symptomatic until they develop advanced stages of the disease, and the pancreas is vulnerable to a variety of complications when examined. Now optical technology — developed by Vadim Backman, professor of biomedical engineering, and tested in collaboration with doctors at Evanston Northwestern Healthcare — shows promise for identifying pancreatic cancer using minimally invasive techniques.

There is currently no effective screening method for pancreatic cancer. Most cancers in the pancreas originate from the main pancreatic duct, a 10-centimeter-long duct that perforates the duodenum, the first and shortest part of the small intestine. Examining the pancreatic duct is a difficult and risky procedure, with a 20 percent chance of serious complications. And, since the pancreas produces several vital enzymes and hormones, including insulin, removal of the organ is not a viable option.

Field effect
Using the same optical technology that has been proven successful in detecting early-stage colon cancer (see spring 2006 By Design), Backman’s research team has detected nanoscale cellular changes in the duodenum that indicate the presence of pancreatic cancer.

“We can take measurements safely in the duodenum and use a biological phenomenon called the ‘field effect’ to our advantage,” Backman says. “If you have a precancerous or cancerous lesion in the pancreas, even tissue that looks normal and is away from the lesion will have molecular and other kinds of abnormal changes. No one can detect these changes earlier than we can.”

The field effect is a phenomenon Backman first used in developing optical techniques to detect colon cancer. The basic premise is that cancerous cells make bad neighbors: Their presence causes submicroscopic changes in all of their surrounding cells. In the case of colon cancer, Backman’s research team has shown the ability to detect cancer by taking measurements at the base of the colon in the rectum. Their new work in pancreatic cancer differs in that it takes measurements in a neighboring organ.

“In many regards, this initial effort was somewhat of a fishing expedition,” Backman says. “When we began this research, there was no scientific evidence that cells in the duodenum would indicate the presence of pancreatic cancer.”

Even without previous studies to help establish a proof of concept, the National Science Foundation saw the potential in the research. “We were so encouraged by the successes with colon cancer research that we decided to drive the research in a different direction,” says Leon Esterowitz, the NSF program officer who funded the initial research. “For pancreatic cancer, it’s not only critical to detect it early, or even before it becomes cancerous, but in many cases it is really the only hope.”

In order to develop the clinical trial of the technology, which was also funded by the National Institutes of Health, Backman and graduate student Yang Liu teamed with Randall Brand, a gastroenterologist with Evanston Northwestern Healthcare who specializes in pancreatic cancer and an associate professor of medicine at Northwestern’s Feinberg School of Medicine, and Hemant Roy, director of research for the section of gastroenterology at Evanston Northwestern Healthcare and associate professor of medicine at the Feinberg School. The team took biopsies from the duodena of 51 patients — 19 already diagnosed with pancreatic cancer and 32 without the disease. The biopsies were taken using standard low-risk endoscopic techniques. While all of the biopsies appeared normal using traditional microscopy, optical tests detected differences between normal and cancerous tissue.

Early-stage success
During the optical testing, a xenon lamp shines intense white light through a series of filters and lenses onto the tissue. The light refracts through the outermost layer of the tissue and scatters into a spectrograph, which separates the light into its component wavelengths and measures them. Another sensor then captures the results for analysis by a computer.

In the trial, the researchers were able to use the same optical markers used in their colon cancer research to differentiate cancerous and normal biopsies with nearly 100 percent accuracy. The clearest results came from patients with early-stage cancer.

“We also found that the diagnostic performance of the technique is not compromised by risk factors in the patients,” says Liu, who is now a senior scientist at Johnson & Johnson Consumer and Personal Products Worldwide. “The markers don’t depend on age. They do not change if the patient is a smoker, and they do not change with the location, stage, or size of the tumor in the pancreas.”

While the survival rate for patients diagnosed with late-stage cancers is low, treatment options are much better for early-stage cancers. If detected early, when a tumor can be removed, the survival rate is anywhere from 50 to 100 percent.

Clinical use of the technology is at least three to five years away, and further trials need to be conducted. “Besides improving upon the technology, we need to determine whether other medical conditions — including other cancer types or diseases of the pancreas, such as chronic pancreatitis or acute pancreatitis — can be distinguished with our technology from pancreatic cancer,” says Brand. “It is also important for us to validate our prediction rule on a larger number of pancreatic cancer cases as well as on different control groups.”

The results of the first clinical trial were published in the journal Clinical Cancer Research in August. Larger clinical trials involving approximately 200 patients are under way at Evanston Northwestern Hospital, and addition clinical trials for the colon cancer work are ongoing. Backman has also founded a company, American BioOptics Inc., to fully develop the technology for commercialization.

Backman and his research team are also studying whether their biophotonic approach can be used to detect other types of cancer, such as lung and breast cancer. “Our hope is that biophotonics will change the way we screen for cancer and allow for early detection and improved treatment options,” Backman says.

If Backman and his team are successful, a simple ray of light will become a powerful tool that will save thousands of lives.

—Kyle Delaney