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MEETING THE CHALLENGES OF PANCREATIC CANCER

BY STEPHANIE STEMMLER

Every few years, as he pursues breakthroughs for one of the world’s most notoriously difficult cancers to treat, William Hawkins, MD, says he feels like the first man who walked on the moon. “When you have an idea, and you test it in the laboratory, and you find a new insight that no one else has known previously, that’s cool,” he says. “It pushes the frontier of cancer research that much closer to effective treatments for my patients. It really is like boldly going where no one has gone before.”

Hawkins is an internationally recognized pancreatic surgeon and cancer researcher who treats patients at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. He has spent nearly two decades expanding treatment options for people with pancreatic cancer and currently leads a national effort, funded by the National Cancer Institute, to identify new insight and treatments into this deadly disease. And the effort is paying off.

10 percent

This year, for the first time, the American Cancer Society notes that the five-year relative survival rate for some stages of pancreatic cancer has reached 10%. (According to the Cancer Society: “A relative survival rate compares people with the same type and stage of pancreatic cancer to people in the overall population.”) While that number may seem low, it is significant.

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WILLIAM HAWKINS, MD, TALKS WITH PANCREATIC CANCER SURVIVOR EDIE CORNELL-SMITH DURING AN ANNUAL EVENT ON SEPTEMBER 28, 2018.
hoto by Matt Miller, Washington University School of Medicine

“When I started my research 15 years ago, the relative five-year survival rate for pancreatic cancer was about 4%. Now it’s 10%. And now I have an aha moment in my laboratory about every other year,” Hawkins says. “The discoveries made in my lab and by other researchers around the country collectively mean we are making steady strides toward understanding this disease and finding more effective treatments.”

Detecting and treating cancer of the pancreas is complicated. The pancreas, located deep in the abdomen behind the stomach, helps the body regulate blood sugar and manufactures enzymes that aid in the digestion of food. It has a naturally immune-suppressive environment; that is, it tamps down the body’s immune system so that it can do its job. But because the pancreas has this ability, its immune cells initially don’t recognize and attack cancer cells when they appear. That reality, called masking, allows a cancer tumor to silently grow, often remaining undetected until the cancer spreads. There are few, if any, symptoms in the early stages of pancreatic cancer and, in the majority of cases, it is diagnosed by accident, perhaps when a person undergoes a CT scan for a different reason.

There are no routine screening tests to detect pancreatic cancer. As it grows or spreads in the later stages, however, symptoms include jaundice (yellowing of the skin and whites of the eyes), abdominal pain radiating to the back, dark-colored urine, unanticipated weight loss and loss of appetite. Specialists don’t know with certainty what causes cancer to form in the pancreas, but there are several known risk factors, including smoking, which appears to double the risk for developing pancreatic cancer, as well as age, obesity, diabetes and chronic inflammation of the pancreas. For those with a family history of the disease, doctors may recommend an MRI scan or an endoscopic ultrasound to check for any signs of developing cancer. Typically, no imaging tests are recommended for the general population unless symptoms are apparent.

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COLORED SCANNING ELECTRON MICROGRAPH IMAGE OF PANCREATIC CANCER CELLS.
Image courtesy of Science Photo Library / Anne Weston, Francis Crick Institute

Can pancreatic cancer be prevented? Perhaps. There are ways to mitigate lifestyle risk factors: avoid smoking, maintain a healthy weight, for example. But pancreatic cancer has been diagnosed even in otherwise healthy individuals, so researchers are working to determine effective methods of early detection.

Promising treatments

As challenging as it is to detect pancreatic cancer, it’s even more challenging to treat. Current options include chemotherapy, radiation or surgery, or a combination of these. Among other considerations, the type of cancer, its location and whether or not it has metastasized, or spread, determine the best treatment options.

A look at the anatomy and placement of the pancreas makes the complications of cancer treatment more easily understood. Shaped like a tadpole, the organ has a thin end, called the tail, and a round end, called the head. The pancreas is surrounded by—or connected to—the liver, small intestine, bile duct, spleen, stomach and gallbladder.

“I describe the area as Grand Central Station,” says Hawkins, “with lines coming in and going out.” He also notes that the pancreas sits atop and shares a blood supply with the small bowel and the liver. And it’s attached to the first few inches of small bowel, which connects the stomach to the small intestine. In addition, the bile duct traverses the pancreas, carrying bile from the liver and gallbladder to the rest of the digestive tract.

SEEING PEOPLE SURVIVE AND THRIVE. THAT’S WHAT PUSHES ME. WE NEED MORE OF THAT.

WILLIAM HAWKINS, MD

Surgery is the definitive treatment when a cancer tumor is small and contained within the pancreas; however most patients aren’t eligible for surgery because their cancers are too advanced by the time symptoms appear. Almost 75% of all small pancreatic tumors are found in the head of the pancreas; these can be removed in a complicated operation called the Whipple procedure. During this surgery, a surgeon removes the head of the pancreas, and a portion of the small intestine and stomach, as well as the gallbladder and a portion of the bile duct. What’s left is then reconnected to restore the digestive tract. Two decades ago, the mortality rate following this procedure averaged 20% in the United States, but thanks to further advancements and growing surgical expertise, that rate has dropped to 1% to 2% at high-volume centers, including Barnes-Jewish Hospital.

The advent of minimally invasive and robotic surgery to treat localized pancreatic cancer is among the most exciting recent advances. These procedures result in less pain and faster recoveries for patients, and they deliver outcomes that are on par with more traditional open surgical procedures. In 2017, Washington University pancreatic surgeon Dominic Sanford, MD, was the first to perform a minimally invasive Whipple procedure at Barnes-Jewish Hospital. And over the last four years, Sanford and Washington University surgeon Chet Hammill, MD, have incorporated new tools and techniques that have allowed more people to qualify for minimally invasive procedures.

In rare cases, Hawkins says, removal of the entire pancreas is recommended, a procedure the surgery team performs about a dozen times per year. This option also requires removal of the gallbladder, part of the stomach and small intestine, and the spleen. People undergoing this procedure will be dependent on insulin injections and medications to help manage blood-sugar levels and digestion.

Hawkins also notes that treatment with chemotherapy prior to surgery, called neoadjuvant chemotherapy, has helped to shrink larger, locally aggressive tumors so they can then be surgically removed. “Surgery by itself is typically an option for about 20% of patients because we rarely catch the cancer early,” Hawkins says. “But we have been able to increase the number of candidates for surgery by using neoadjuvant chemotherapy.”

New drugs and immunotherapy

Hawkins says the next frontier is tackling pancreatic cancer that has spread outside of the pancreas. A new drug, called olaparib, has been approved by the Food and Drug Administration to treat a specific type of metastatic pancreatic cancer. Clinical trials found that the drug, given after a regimen of chemotherapy, reduced the risk of disease progression in many patients.

At Washington University School of Medicine, a team of researchers has identified another promising drug called ACXT-3102, which is now on the cusp of clinical-trial testing. Hawkins and colleagues, including William Gillanders, MD, Washington University surgical oncologist at Barnes-Jewish Hospital, and Robert Schreiber, PhD, Washington University immunologist, also are working to develop personalized pancreatic cancer vaccines tailored to a patient’s tumor. Given after surgery, the vaccine stimulates the body’s own immune system to fight off any remaining cancer cells.

“We’ve created personalized vaccines for about 15 patients so far,” says Hawkins. To date, he says, the research shows the vaccines are safe and are able to recognize cancer tumor cells. There is not yet enough data to say whether a vaccine can offer a cure. “We do know, however, that immunotherapy is an exciting and promising path to pursue.”

Other investigations are focused on testing new drug combinations to improve outcomes and new methods to deliver chemotherapy drugs directly to the tumor.

Survive and thrive

Hawkins says the results of myriad efforts to battle pancreatic cancer are vividly obvious at an event called Survive and Thrive. Held annually in conjunction with Pedal the Cause, a program that raises money and awareness for cancer research at Siteman Cancer Center, Survive and Thrive brings together doctors, surgeons, researchers, patients and their families. “We’ve held our event for about 13 years,” says Hawkins. “Last year, more than 50 survivors of pancreas cancer attended, all at least five years past treatment. It was wonderful to see.”

Hawkins also serves as team captain for the Pancreas Cancer Road Warriors, a cycling team that participates in Pedal the Cause and has raised more than $400,000 for pancreatic cancer research. He is quick to thank all donors who give to Siteman Cancer Center. “Most importantly, we thank the people who participate in clinical trials. We need better options for them and others, but we can’t do it without their help.” He adds: “Seeing people survive and thrive. That’s what pushes me. We need more of that.”


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