The Impact and Future of the Childhood Cancer Survivor Study: An Interview with Greg Armstrong, M.D.
09/14/2016
September is Childhood Cancer Awareness month, an opportunity to learn more about pediatric cancer. Thanks to treatment advances, 83% of children diagnosed with cancer will survive at least 5 years after diagnosis. Unfortunately, many of these survivors will experience late effects, health problems later in life that are related to the cancer treatments they received as children. The NCI-supported Childhood Cancer Survivor Study (CCSS) has helped to identify late effects of childhood cancer treatments, and to develop strategies for preventing or better managing these effects, with the aim of improving survivors’ quality of life and long-term survival. In this interview, Greg Armstrong, M.D., of St. Jude Children’s Research Hospital, principal investigator of the CCSS, discusses some recent findings from the long-running study and its future directions.
The Impact and Future of the Childhood Cancer Survivor Study: An Interview with Greg Armstrong, M.D.
September 14, 2016 by NCI Staff
September is Childhood Cancer Awareness month, an opportunity to learn more about pediatric cancer. Thanks to treatment advances, 83% of children diagnosed with cancer will survive at least 5 years after diagnosis. Unfortunately, many of these survivors will experience late effects, health problems later in life that are related to the cancer treatments they received as children.
The NCI-supported Childhood Cancer Survivor Study(CCSS) has helped to identify late effects of childhood cancer treatments, and to develop strategies for preventing or better managing these effects, with the aim of improving survivors’ quality of life and long-term survival. In this interview, Greg Armstrong, M.D., of St. Jude Children’s Research Hospital, principal investigator of the CCSS, discusses some recent findings from the long-running study and its future directions.
Why are pediatric cancer survivors at risk for late effects?
Cancer is a very foul enemy, and it takes intensive therapies to beat it. Aggressive surgery, radiation therapy, and chemotherapy can all impact a patient’s risk for long-term health problems. For pediatric cancer patients, those therapies are applied to a developing body, which has many dividing cells that are especially vulnerable to damage from these harsh therapies.
One example of a late effect is a second cancer, a new primary cancer that arises later and is distinct from the patient's original cancer—that is, it is not a recurrence of the childhood cancer. For instance, we’ve learned from the CCSS and other studies that more than 30% of girls who had Hodgkin lymphoma and received chest-directed radiation therapy will develop breast cancer by age 50.
Late effects occur in many different body systems, depending on the site of the cancer and the treatment. For example, other late effects include heart failure, nerve damage, endocrine disorders, and infertility.
Can you describe the Childhood Cancer Survivor Study in more detail?
The CCSS is a cohort study, which means that participants are enrolled after receiving a cancer diagnosis and treatment. After enrollment, follow up on the study will occur periodically across the participant’s lifespan. We follow up primarily by administering self-report surveys.
To be eligible for enrollment, a person has to have been diagnosed with cancer before the age of 21, at one of 31 collaborating institutions in the United States. In addition, they have to be 5 or more years past the date of diagnosis.
The original study population included survivors diagnosed between 1970-1986. In the last year, we have expanded the cohort to include survivors diagnosed between 1987-1999, increasing the number of participants from 14,000 to more than 24,000.
What has been learned from the expanded cohort?
In a study we published in the New England Journal of Medicine in March of this year, we showed that childhood cancer survivors from the 1990s are living longer than those diagnosed in the 1970s and 1980s. Since the 1970s, pediatric oncologists have learned that certain cancers can be treated with less intensive therapies. Consequently, the risk of death from late effects has dropped, and lifespans have lengthened, for survivors of certain childhood cancers.
That was pretty groundbreaking work because it was the first evidence that childhood cancer survivors in the more modern era are living longer; this was hypothesized for many years, but it took the strength of this large cohort to prove it.
How have pediatric cancer treatment strategies changed over the past decades to reduce late effects?
The original study population of survivors diagnosed in the 1970s and the early 1980s taught us a lot about the toxicities of cancer therapies, which helped lead to a reduction in the use of these therapies for some cancers.
For example, we’ve reduced and almost eliminated the use of cranial radiation for the treatment of acute lymphoblastic leukemia, and that has improved the cognitive health of these survivors. Likewise, Hodgkin lymphoma was previously treated with very high doses of radiation and chemotherapy, which, we learned, increases survivors’ risks of secondary leukemia and infertility. Over time, we reduced or replaced those agents with other, less toxic agents.
We have also learned that there are certain patients who need more aggressive therapy to improve their chances of survival. For example, over the last few decades we have intensified therapy for high-risk neuroblastoma, and we can expect more late effects in those survivors.
Does genetics play a role in the risk of developing late effects?
The role of genetics in late effects is relatively unknown, and it is something the CCSS is investigating. We are collaborating with NCI’s Division of Cancer Epidemiology and Genetics (DCEG) to analyze the germline genetics of childhood cancer survivors. We have now analyzed genetic variants in the genomes of more than 5,700 survivors, and we currently have two genome-wide association studies investigating survivors’ genetic susceptibility to second cancers—specifically, breast cancer and a type of brain cancer called meningioma. Within the next year, DCEG will also complete whole-exome sequencing of those 5,700 participants, so it will be a pretty rich dataset.
The great thing is, these data will be an open resource for all investigators; another function of the CCSS is to be a resource for survivorship research.
What intervention and prevention strategies for late effects have resulted from CCSS research?
It is not enough for the CCSS to simply identify and enumerate late effects. We very much need to intervene and change the course of pediatric cancer care. As such, the CCSS has a number of ongoing intervention studies.
For example, the EMPOWER study, led by Kevin Oeffinger, M.D., of Memorial Sloan Kettering Cancer Center, focuses on increasing mammography screening rates among female survivors of childhood cancer who had chest-directed radiation therapy and, therefore, are at long-term risk for breast cancer. At the American Society of Clinical Oncology annual meeting this spring, Dr. Oeffinger reported findings from the studywhich showed that providing survivors with information and telephone counseling on their treatment exposure and risk for breast cancer doubled the rate of mammography screening among survivors.
What are some other future directions for the CCSS?
For one thing, we’re conducting additional intervention studies for late effects of childhood cancer, such as the Advancing Survivors Knowledge (ASK) About Skin Cancer study. The goal of the ASK study is to improve screening rates for skin cancer, because childhood cancer survivors are at a threefold greater risk for melanoma and 40-fold greater risk for nonmelanoma skin cancer than the general population. The ASK study uses telemedicineto interact with participants, and participants have been very open to this approach. Another intervention trial, the EQUAL study, aims to reduce obesity in survivors of acute lymphoblastic leukemia.
The CCSS is also expanding the use of mobile health technology. We have 24,000 participants scattered across the country, so we’ll never be able to assess them all systematically in a clinical setting. To address this, we are collaborating with the Health eHeart Study at the University of California, San Francisco, to begin using cell phones to collect health-related data for the CCSS.
For example, in our surveys we ask if the participant has high blood pressure. Now we can send them blood pressure cuffs that connect to their phones and ask them to send us weekly blood pressure readings. Other sensors that can be linked to mobile phones—such as electrocardiogram monitors, weight scales, and physical activity monitors (like Fitbit)—can be used to capture data from survivors that are geographically dispersed across the country.
With our previous work and these new directions, the CCSS is poised to make a significant and lasting influence on the field of childhood cancer survivorship for years to come.
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