Treatments for childhood cancer are often intense and carry an increased risk of lifelong health problems for survivors. An analysis of 23,600 childhood cancer survivors, median age 28 years (range 5-63), in the Childhood Cancer Survivor Study (CCSS), funded by the National Institutes of Health, found that the rate of severe health problems occurring five or more years after diagnosis has declined over time. 
The results of the study were presented at the 53rd annual meeting of the American Society of Clinical Oncology (ASCO) Annual Meeting.
The rate of such problems by 15 years after diagnosis was 8.8% among survivors diagnosed in the 1990s, but 10.1% among those diagnosed in the 1980s and 12.7% among those diagnosed in the 1970s (per 10 years, HR 0.84 [95% CI = 0.80-0.89]).
According to the researchers, the association with diagnosis decade was attenuated (HR 0.92 [0.85-1.00]) when detailed treatment data were included in the model, indicating that treatment reductions mediated risk.
The largest decreases over three decades occurred among survivors with Wilms’ tumor (43% | (HR 0.57 [0.46-0.70]) and Hodgkin lymphoma (25% | (HR 0.75 [0.65-0.85]). Other decreases were noticed among survivors with astrocytoma (HR 0.77 [0.64-0.92]), non-Hodgkin lymphoma (HR 0.79 [0.63-0.99]), and acute lymphoblastic leukemia (HR 0.86 [0.76-0.98]).
Treatment and supportive care
The decline of severe health problems occurring five or more years after diagnosis coincided with changes in pediatric cancer therapy and follow-up care. These changes include, for example, reductions in the use and dose of radiation therapy as well as chemotherapies including anthracyclines for treatment of acute lymphoblastic leukemia (ALL), Hodgkin lymphoma and Wilms tumor.
While these therapies are being used in treating patients, they leave survivors at increased risk for developing second cancers, heart failure and other serious health problems.
Over the last decade, survivors have benefited from improved follow-up care, including risk-based health screening guidelines. This approach has resulted in early detection of late effects of cancer therapy and has shown a lifesaving difference. In turn, these advances in treatment and supportive care have improved the five-year survival rate after childhood cancer diagnosis, from 58% in the 1970s to 84% today. A previous report from the Childhood Cancer Survivor Study showed that changes in treatment over three decades lowered the chance of dying from late effects of therapy among childhood cancer survivors by 6.4%. 
“This is the first comprehensive study to demonstrate how changes in treatments over time have impacted the occurrence of late effects experienced by childhood cancer survivors,” explained lead study author Todd M. Gibson, PhD, an Assistant Member at St. Jude Children’s Research Hospital in Memphis, TN.
“From our findings, it is clear that survivors diagnosed and treated in more modern treatment eras are doing better. Not only are more children being cured, but they also have lower risk for developing serious health problems due to cancer treatment later in life,” Gibson further noted.
Researchers analyzed data from the CCSS, which uses periodic surveys to explore long-term health outcomes in survivors of childhood cancer who were diagnosed between 1970 and 1999 and survived at least five years after diagnosis.
This analysis focused on the incidence of severe, disabling, life-threatening or fatal health problems arising within 15 years of childhood cancer diagnosis. The median patient age was 28 years, with a median of 21 years from diagnosis. The researchers gathered information about the health problems from surveys (self-reported data) and from the National Death Index, for cases where survivors died as a result of late effects of treatment.
The 15-year cumulative incidence of severe health conditions decreased from 12.7% among childhood cancer survivors diagnosed in the 1970s to 10.1% and 8.8% among those diagnosed in the 1980s and 1990s, respectively.
By cancer type, over the three decades the occurrence of severe health problems by 15 years after diagnosis decreased from:
- 13% to 5% among survivors of Wilms’ tumor (a rare kidney cancer)
- 18% to 11% among survivors of Hodgkin lymphoma
- 15% to 9% among survivors of astrocytoma (the second most common childhood cancer)
- 10% to 6% among survivors of non-Hodgkin lymphoma
- 9% to 7% among survivors of acute lymphoblastic leukemia (the most common childhood cancer)
Treatment related late health effects
The greatest decreases were largely found by a reduced incidence of endocrine conditions (4.0% in the 1970s versus 1.6% in the 1990s; HR 0.66 [0.59-0.73]) and subsequent cancers (2.4% in the 1970s versus 1.6% in the 1990s; HR 0.85 [0.76-0.96]). Significant reductions were also found for gastrointestinal cancers (HR 0.80 [0.66-0.97]) and neurological conditions, but not cardiac or pulmonary conditions (HR 0.77 [0.65-0.91]).
“While we are glad to see these improvements,” Gibson noted, “a key point is that we have not identified any age or time since diagnosis when survivors no longer need to be concerned about their risk of treatment-related late health effects, as they seem to persist throughout their lifetime.”
For example, researchers found no reductions in severe health problems among survivors of other types of childhood cancers, such as neuroblastoma, acute myeloid leukemia (AML), soft-tissue sarcoma, and osteosarcoma.
“We were a little surprised that the incidence of severe cardiovascular disease did not decrease, knowing that deaths from cardiovascular disease dropped among survivors in recent decades,” explained Gibson. “This is a reminder that survivors continue to have an increased risk for serious health problems compared to the general population and need to be followed closely.”
“Perhaps no other area of oncology has seen such dramatic progress in treatment over the past decades as childhood cancer.” said Timothy D. Gilligan, MD, MSc, Vice-Chair for Education, and Associate Professor of Medicine at the Cleveland Clinic Taussig Cancer Institute and an ASCO Expert not associated with this study.
“As a result of advances in treatment and care, children with cancer are not only living longer, they are benefitting from reductions in the long-term side-effects of cancer treatment. These results show how important it is to fund and conduct studies of cancer survivors,” Gilligan added.
The researchers plan to delve deeper into specific health conditions, beyond the broad categories captured in this analysis. They would also like to follow survivors beyond 15 years after diagnosis and explore how late treatment effects intersect with aging.
Last editorial review: June 3, 2017
Featured Image: The Small Bear needs a Doctor. Courtesy: © 2017 Fotolia. Used with permission. Photo 1.0: Arnaud Scherpereel, MD, PhD, University Hospital of Lille, France. Courtesy: © 2017 ASCO/Scott Morgan.
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