UF Is Home To National Statistical Data Center For Childrens Cancer Research
By Melanie Fridl Ross
most parents, Lisa and Keith Cannady can proudly recite all the important
facts and figures about their daughter. Marissa is 6 years old. She was
born on the 4th of July. She weighed 7 pounds, 4 ounces at birth, stood
39.5 inches tall four years later. And so on.
But the Cannadys data bank delves even deeper. They also monitor an entirelydifferent set of digits and dates, numbers that signal how Marissa is faring in the battle against cancer. The size of the tumor nestled in her right thighbone. Her latest blood counts. The drug doses that comprise her chemotherapy cocktail. The odds shell survive the battle.
While these statistics merit careful review by Marissas parents and doctors, they also receive attention somewhere else: the Childrens Oncology Group Research Data Center at the University of Florida International Center for Childhood Cancer Research, the first stop for research data from virtually every pediatric cancer patient in the United States and beyond.
The Childrens Oncology Group is a newly created, federally supported consortium that pools resources to design, conduct and analyze studies of pediatric cancer therapies worldwide. Clinicians throughout the United States, Canada, Switzerland, Australia and parts of Europe funnel their data to UF for analysis.
The reason is simple: During the past 25 years, many of the major treatment breakthroughs have arisen out of the collaborative efforts of research groups around the world. Such cooperation, UF officials say, helps produce faster research results and hastens the discovery of cures.
The information pours into their offices
at a dizzying rate. Using sophisticated computational tools, they scrutinize
data from about 240 institutions participating in randomized clinical
trials to help determine what is working and what isnt. Is a once-incurable
cancer becoming vulnerable to a new drug regimen? Are kids responding
poorly to a certain medication? Is a therapy enabling them to spend more
time in school or avoid side effects?
Back in the 50s it was recognized that cancer in childhood is rare. And cancer in children often has many different manifestations we dont see in adults, says pediatric oncologist John Graham-Pole, a professor of pediatrics at UFs College of Medicine and the UF Shands Cancer Center, and principal investigator for the UF clinical membership of the Childrens Oncology Group. To learn anything about this disease, you need the numbers. One institution alone could not possibly have enough patients. It became evident that the only way to work was to network nationally and, increasingly, throughout the world.
The cooperative approach has been scientifically proven to increase survival rates in all forms of leukemia, lymphomas and solid tumors. In addition, the research has helped practitioners identify improvements in the treatment of childhood cancers, and contributed to a better understanding of cancer cause and development.
UF statisticians design research protocols and aid in the development of research questions. They also monitor the performance of member institutions and conduct statistical analyses as data are gathered. On average, 100 clinical trials are under way on any given day, covering all major childhood malignancies, according to Brad Pollock, an associate professor and interim chair of the College of Medicines Department of Health Policy and Epidemiology at UF, and associate director for cancer control at the UF Shands Cancer Center. Pollock also has been appointed to the Medical Scientific Advisory Board for the National Childhood Cancer Foundation, the organization that sponsors the new group.
This puts us on the map in terms of being a major institute for pediatric cancer research, Pollock says. Harvard, Johns Hopkins, Yale, USC, Stanford ... every major medical center with a childhood cancer research program belongs to this consortium. Collectively, about 65 percent of all children with cancer get placed on one of these treatment protocols. This is the standard of care for childhood cancer.
The National Cancer Institute gives UF about $2.5 million a year for its pediatric cancer research programs. Approximately $2 million of that supports direct costs of the data center, headed by statistics professor Jonathan Shuster and staffed by 32 statisticians, systems analysts, data managers and administrators. The other half million is earmarked for research on pediatric cancer prevention and control.
The data center, part of the Department of Statistics in UFs College of Liberal Arts and Sciences, serves as the repository for the research data submitted by member institutions and by centralized laboratories and tumor banks that analyze cancer specimens.
Center officials track timeliness of data submission and police quality of the institutions involvement in the studies. They leave no stone unturned, analyzing whether appropriate laboratory tests have been done, how drugs were administered and monitored, and how various malignancies were categorized based on pathological data.
To aid in these efforts, UF has developed a new Web-based system that researchers use for remote data entry.
The Childrens Oncology Group includes pediatric oncologists, surgeons, pathologists, psychologists, radiation oncologists, nurses, pharmacists and clinical research associates who pool clinical case material and laboratory resources, and serve on numerous disease, discipline and scientific support committees.
The Pediatric Oncology Group, the Childrens Cancer Group, the National Wilms Tumor Study Group and the Intergroup Rhabdomyosarcoma Study Group united last spring to create the organization, now the largest pediatric cooperative group in existence, consisting of about 240 hospitals, cancer centers and academic medical centers.
UF has been a member of the Pediatric Oncology Group since it was formed in 1980 and was the statistical center for that organization as well. The merger reduces the number of NCI-supported cooperative research groups from 12 to nine; the others are dedicated to the treatment of adult cancers.
A Bump On The Knee
Marissas ordeal started when she was in kindergarten, after she bumped her knee on the playground.
She told us about it when she came home, says her father, Keith. She said her knee was bothering her a little bit, but after that she seemed fine. Two weeks later she bumped her knee again on the ottoman in our house, and my wife took her to have her knee checked. We saw a little swelling, and she was favoring it a bit. The doctor where we lived said it was a bruised muscle.
After her discomfort persisted, the Cannadys took their daughter to two other doctors. After one raised the specter of cancer, they rushed Marissa to the UF Shands Cancer Center from their home in the Florida Panhandle.
Graham-Pole confirmed their daughter had osteosarcoma, a form of bone cancer, and within days she began chemotherapy, enrolling in a national trial designed to improve treatment for these patients.
Previous attempts to increase the amount of chemotherapy given raised the risk of toxic effects. So Marissa and other study participants also received a drug designed to protect the heart.
He said, This is whats available: We can give her something that has worked in the past or we can try her on something using different doses, and shed probably spend less time on the treatment, says Marissas mother, Lisa. We looked at that and thought that would be good because we wanted to get this over with. We wanted it to be effective, but we wanted to get this over with.
A few months later, after the drugs had begun to shrink the tumor, Marissa underwent an above-the-knee amputation using a technique to preserve mobility. Once her lower leg and knee joint were removed, the ankle joint was rotated and attached to become the new knee joint. Marissa wears a short prosthetic limb to complete the lower portion of her leg. Her prognosis is good.
Behind The Numbers
Shuster will likely never meet Marissa. But he never forgets whos behind his work.
As statisticians, we analyze numbers, but were never unaware of the children, he says. You never lose sight of that. Thats who those numbers represent.
Shuster and his colleagues act as watchdogs, studying the data as they come in to see which treatments are working and which arent.
You just want to know what the truth is out there, he says. In a nutshell, were there to make sure that the study is not doing something that is unexpected.
Shuster, also a professor of statistics at UF, thinks back to 1994, to a study of about 300 children with leukemia. Researchers were evaluating whether outcomes could be improved by altering when certain drugs were administered.
Patients started having seizures in fairly large numbers, and because we had a finger on the pulse of the study we watch our studies so closely we found it really quickly, Shuster says. Thats where our collective experience helps. If everyone is feeding their data into the system in a timely way you can find out about the problem and you can correct it much faster, and when you make a correction it goes national.
Statisticians also have helped uncover drug interactions and evaluated findings that ultimately revised the standard of care. Thanks to seven years worth of data, about 20 percent of children with neuroblastoma now undergo successful surgery and are spared chemotherapy or radiation, which used to be the traditional therapy, Shuster says. About 95 percent of them are cured.
In addition, findings from a study dating to the early 1980s showed a combination of three drugs placed directly into the spinal fluid was much more effective than a single drug for patients whose leukemia recurred in the central nervous system.
We had to curtail the study and give the patients who were on the other treatment the triple drugs, which just did a much better job of protecting the central nervous system, Shuster says. If youre watching a study carefully and you have large numbers, when one treatment turns out a lot better you find out soon enough so patients on the other treatment can benefit.
Since the 1950s, cancer mortality in children has dropped 55 percent, and more than 70 percent of children with cancer are cured and grow up to be healthy adults, says Shuster. In comparison, the death rate has declined just 10 percent in adults, only 1 to 2 percent of whom enroll in group trials.
As cure rates continue to rise for children with cancer, research efforts have been broadened to look at the long-term effects of cancer therapy and how it affects the lives of childhood cancer survivors.
Some of the drugs, although they cure children of cancer, leave them with heart problems, learning disabilities and other difficulties, Shuster says. This is another area were very concerned with. Curing them is not enough.
Says Lisa Cannady, Marissas mother, You dont want anybody to have to go through what your child had to go through. You definitely hope that whatever the findings, good or bad, theyre going to help another child along the way.
Professor, Department of Pediatrics
Associate Professor and Interim Chair, Department of Health Policy and Epidemiology
(352) 395-8040 x8-6538