Going toe to toe with a rapid, ruthless killer like pancreatic cancer requires more than business as usual. With a median survival of six months after diagnosis, time is of the essence. Now a joint effort by the Hutchinson Center and Group Health Cooperative is uniquely poised to make progress against pancreatic cancer by being as swift and aggressive as the disease.
The PACIFIC ("Pancreatic Cancer Investigation: Finding Causes") study is comprised of almost 1,500 pancreatic-cancer cases and controls from two health-maintenance organizations (HMOs) with infrastructure to support ultra-rapid case identification within 10 days of diagnosis. Led by Dr. Meg Mandelson, associate investigator for Group Health's Center for Health Studies, and Dr. John Potter, director of the Public Health Sciences Division, the study's rapid-recruitment methods might allow researchers to finally understand the full spectrum of the disease.
Fourth leading cause of death
Funded by the National Cancer Institute, study staff at Group Health and Northern California Kaiser Permanente's Division of Research have been recruiting patients for the project since July. Recruitment for one of the largest epidemiologic studies of pancreatic cancer ever undertaken continues for three and a half years.
"Pancreas cancer is one of the most devastating cancers," said Potter of the fourth leading cause of cancer death in the United States. "Most patients with this cancer die quickly and in pain. Whereas we now do much better with survival from some cancers, pancreas remains difficult and miserable.
"In many studies, patients die so early after diagnosis, it is not possible to interview them. We know very little about what causes it, beyond knowing for sure that the risk is higher in smokers. Here in Seattle and in collaboration with our colleagues in California, we will have the best chance to understand causes."
The researchers' intention is for the PACIFIC study to be a foundation for an expanding program of pancreas-cancer research, said Mandelson, also an associate member of PHS.
"Our interdisciplinary group of investigators will be studying environmental and lifestyle risk, genetic predisposition and biomarkers for early detection," she said. "In addition to obtaining interview data and biospecimens, the study also has access to archival tissue, comprehensive electronic medical records and associated treatment and outcomes on study participants."
The PACIFIC study is the population-science portion of an emerging program in pancreatic-cancer studies at the Center. Part of those efforts includes the recent recruitment of Dr. Sunil Hingorani, a Clinical Research Division scientist who studies pancreatic cancer in mice (see related story) to illuminate early-detection methods. Additionally, there is ongoing collaboration with affiliate investigator Dr. Teri Brentnall at the University of Washington, a leader in familial studies of pancreatic cancer and in identifying strategies for surveillance.
The study sites in Washington and California have established a surveillance system within their patient databases to daily monitor for possible pancreatic-cancer cases. For example, the system flags patients with certain elevated lab results or those scheduled for pancreatic imaging. Study staff members watch those cases, and if there is a diagnosis of pancreatic cancer, they ask the patient's physician for permission to contact the patient. Staff members contact those willing to participate in the study one time. The patient answers questions about their medical history, family history, medication use, diet, etc. They also give a blood sample.
Cell lines are being established from the blood specimens. The serum, plasma and DNA are processed and stored at the Center, as well as at the University of Washington's Institute for Public Health Genetics, directed by Dr. Melissa Austin, another study collaborator and an affiliate member of the Center. Study specimens are well-annotated, indicating when they were drawn and processed and how they were stored, along with epidemiologic and clinical characteristics of the cases and controls. With such details linked to the specimens, it will be easier to interpret laboratory findings when specimens are shared between multiple researchers and institutions.
Assessing diet, disparities
Dr. Alan Kristal, a researcher in the Center's Cancer Prevention Program, is leading the dietary investigations for the PACIFIC study. Because there may be a link between diabetes and pancreatic-cancer risk, Kristal will focus on factors that influence insulin resistance, including glycemic load, total carbohydrate intake and consumption of specific types of sugar and dietary fiber. He was also look at participant intake of folate and certain vitamins and amino acids.
The researchers are waiting for about six months' of recruitment data before asking for additional funding to expand the study to include two additional HMO study locations at sites in Southern California and Detroit. These areas have large minority populations, which will allow risk differences by race and ethnicity to be assessed.
The PACIFIC study investigators recently received pilot funding from the Early Detection Research Network to conduct a companion study of patients who are suspected of having pancreatic cancer and are found instead to have pancreatitis-inflammation of the pancreas that may increase risk of cancer — or a different cancer type. Specimens from these patients will serve as an important control group for testing new early detection markers for pancreatic cancer. In addition, some of these study subjects may develop pancreas cancer in the future. "Pancreatic cancer is aggressive and difficult to detect at an early stage. If we can better understand who's at highest risk for developing pancreatic cancer, then we can develop strategies for surveillance and early detection in these high-risk sub-groups," Mandelson said. They are working in partnership with Dr. Michael Hollingsworth at the University of Nebraska Medical Center, home to a pancreatic-cancer biomarker development laboratory.
Mandelson knows she's waging war on an intractable disease, but that fact only strengthens her zeal for answers. "Compared to other cancers, our understanding of pancreatic cancer is very limited. By working within these HMO populations, PACIFIC investigators are perfectly poised to gain new insight into effective prevention, detection and treatment of this cancer," she said.