As they help more children conquer cancer, U physicians are also identifying and managing the spectrum of health challenges these survivors tend to encounter as adults
Jerrad Bergren will always remember Thanksgiving 1998. Diagnosed with acute lymphocytic leukemia shortly after starting fourth grade, Bergren had been receiving chemotherapy and radiation at the University of Minnesota on and off for four years. After two bouts with the cancer and multiple treatments, he finally finished his last round the day after the big family celebration. “It was a happy Thanksgiving,” he says.
Though Bergren, now 23, officially completed his anticancer therapy 10 years ago, he will never be totally done with it. Treatment that’s tough enough to kick cancer also roughs up healthy tissue. As a result, Bergren must deal with special health considerations for the rest of his life.
Fortunately, his doctors at the University will be here for him over the long haul. Once a year, Bergren sees his oncologist, Joseph Neglia, M.D., M.P.H. He undergoes tests to look for signs of brain cancer and heart trouble, two possible side effects of his particular mix of therapies. An endocrinologist helps keep his hormone levels, also affected by the treatments, on track. And he gains valuable advice on lifestyle choices that minimize future risks.
“Other than that, I’m pretty much a free person,” he says. “I’m a pretty lucky guy.”
Part of the contract
Forty years ago, the long-term health of childhood cancer survivors was not a major issue: Few who got the disease lived long enough to experience later-occurring side effects. But as treatment advanced, that changed. More and more children who were diagnosed with cancer survived and began experiencing a variety of health concerns—from learning disabilities to second malignancies—related to the disease itself or to the treatment they received to cure it.
As recognition of so-called late effects grew, so did the conviction that something could and should be done about them.
“I personally believe this is part of a contract that we implicitly enter into with children and families when we start their care,” says Neglia, vice chair of the pediatrics department and section chief of pediatric hematology-oncology. “We’re committed not only to curing the disease but to doing everything possible to restore the patient’s health.”
In the early 1990s, Neglia and former U colleagues Leslie Robison, Ph.D.; Ann Mertens, Ph.D.; and Mark Nesbit, M.D., received a pilot grant from the Children’s Cancer Research Fund to test the feasibility of gathering health data from thousands of people who had survived childhood cancer. The pilot provided the findings the researchers needed to propose, win, and then lead a 26-institution National Institutes of Health study of more than 14,000 survivors of eight types of childhood cancer who had received treatment between 1970 and 1986.
Using powerful statistical tools, the Childhood Cancer Survivor Study (CCSS) has been exploring relationships among various types of cancers, treatment regimens, and health ever since. Through it, researchers have found that, depending on the type of cancer and treatment, childhood cancer survivors may face elevated risks of second cancers, heart problems, abnormal growth, fertility issues, and a host of other complications. Some experience health problems related to their cancer experience; others’ long-term health is very similar to that of the general population.
Discerning the late effects of childhood cancer is just the first step. Knowing what the risks are, survivors like Bergren and their physicians can take steps to prevent, watch for, and head off health problems later in life.
“The study led to the creation of a whole science around what follow-up is important for the patient, not only in terms of recurrence, but also for late outcomes,” Neglia says. “It’s really focused on the restoration of health—on bringing [patients] back to the potential they had before they had the disease.”
An innovator in treating childhood cancer, the University of Minnesota has been a leader in caring for cancer survivors, too. Three years ago, physicians here established the Long-Term Follow-Up Clinic, creating a more formal approach for monitoring and managing the health of individuals who had undergone treatment for cancer as children. Childhood cancer survivors treated at the University are transferred to the clinic five years after diagnosis or three years after blood or marrow transplant. Individuals who received cancer treatment at other institutions are welcome, too.
“We still talk about cancer and recurrence, but the focus really is on long-term effects [patients] may or may not experience,” says clinic director Daniel Mulrooney, M.D., M.S., assistant professor of pediatrics. Together, the physician and patient review detailed records of past treatments and develop a plan for watching for future complications. “Our role is to provide the information,” Mulrooney says.
Survivors like Shari VanPuyvelde know how important that is. Diagnosed with Ewing’s sarcoma when she was 10, VanPuyvelde—now an oncology nurse herself—is managing after-effects of hefty doses of chemotherapy and radiation, including impaired lung and cardiovascular function. About three years ago, she graduated from the care of her pediatric oncologist to the Long-Term Follow-Up Clinic, which she visits periodically for scans and blood work to watch for recurrence of her cancer and emergence of long-term effects of the treatment she received.
“I started after my transplant—first every two months, then every six months; then, after five years, it’s every year for the rest of my life,” she says.
Bergren, who just graduated from chiropractic school and is setting up practice back home in Bovey, Minnesota, doesn’t approach his need for follow-up care with a sense of doom and gloom. Instead, he uses what he learns through visits to the Long-Term Follow-Up Clinic to keep himself in optimal shape.
“They inform me of the meds and the negative side effects, where I’m at now, what I need to pay attention to, and they provide guidance on what I can do to keep my heart healthy,” he says. “It’s just like if you had a family history of heart problems. Education is a hugely important preventive.”
Besides keeping patients informed about special concerns they face because of their health history, the clinic also seeks to inform primary-care physicians about the long-term risks of childhood cancer. A 2006 Institute of Medicine report, From Cancer Patient to Cancer Survivor: Lost in Transition, noted that relatively few health-care professionals receive specific training in caring for cancer survivors and recommended that providers be educated about treatment risks, the value of surveillance and intervention to minimize late effects, and the psychosocial and lifestyle implications for patients.
“The medical community needs to understand the importance of this: After the cure, there are long-term issues,” Mulrooney says. “General pediatricians, internists, family doctors aren’t yet aware of these issues.”
At the end of each clinic visit, Mulrooney not only gives the patient a copy of his or her report, but sends it to the patient’s primary-care physician as well. If they are aware of the extra risks their cancer-survivor patients face, he says, doctors back home can ensure that patients get the tailored attention they need—for example, early mammograms for women who received radiation therapy as girls.
As part of a teaching hospital, the Long-Term Follow-Up Clinic also gives medical students and residents a chance to learn about the special needs of childhood cancer survivors.
“Until now, the care of cancer survivors and discussion of long-term effects has never been a part of medical education,” Mulrooney says. “So this is an opportunity to expose new physicians to these issues.”
Despite tremendous gains, doctors admit they have much to learn about cancer’s late effects. Cancer treatment has changed dramatically since the 1970s, and the health implications for patients of the 1990s and beyond will be different from their predecessors’. But no one knows what form it will take.
Long-Term Follow-Up Clinic patients have the opportunity to help figure that out. Each is invited to participate in ongoing research and enroll in the clinic database so researchers can learn more about correlations between treatments and outcomes.
Mulrooney, for example, is using data gathered from clinic patients to explore the effects of chemotherapy and radiation therapy on the cardiovascular system, in hopes of identifying who is at greatest risk and therefore should be followed most assiduously. Associate professor of pediatrics K. Scott Baker, M.D., M.S., is studying development of the metabolic syndrome after blood and marrow transplantation. Others are looking at correlations between treatment regimens and brain function, school performance, and development of second neoplasms.
Though it plays a key role, the Long-Term Follow-Up Clinic is just one component of the University’s efforts to better understand and manage late effects of childhood cancer.
One big challenge in the CCSS has been finding and obtaining information from patients who completed cancer treatment years or even decades earlier. An international childhood cancer research network launched last December under the leadership of University pediatrics professor Julie Ross, Ph.D., is working to make that easier in the future.
The new Childhood Cancer Research Network streamlines the process for gathering patient data across a consortium of more than 200 cancer centers. Covering the care of up to 90 percent of childhood cancer survivors in the United States and Canada, the network holds tremendous potential for advancing understanding of the causes and effects of childhood cancers because it makes it relatively simple for researchers to obtain the large amounts of patient data needed for a rigorous scientific study.
The network got a big boost in July with the passage of the Conquer Childhood Cancer Act, authored by Senator Norm Coleman and co-sponsored by Senator Amy Klobuchar. The act earmarks $5 million for the registry over the next five years.
“It’s going to be great,” says Ross, who also directs the Division of Pediatric Epidemiology and Clinical Research.
A new Masonic Cancer Center research program, codirected by Baker and Beth Virnig, Ph.D., M.P.H., associate professor of health policy and management in the School of Public Health, gives researchers exploring various aspects of the health of cancer survivors—both children and adults—regular opportunities to come together, learn from one another, and develop better ways to prevent and improve outcomes from late effects. The cross-talk is particularly valuable for helping survivors of childhood cancer as they become adults and begin to consider such issues as how their health concerns might affect their work and careers or their plans to start families.
“We’re all in this together,” Virnig says. “Some of the best insights happen when you get people talking.”
By Mary Hoff
Illustration by Elizabeth Lada