Over the previous two decades, overall survival for children with cancer has improved unevenly.

Survival gains varied by cancer, and the demographic factors of race and ethnicity, economic status, and zip code also seemed to be driving disparities in cancer survival, according to a large population analysis of a national database.

“Cancers such as bone tumors and many central nervous system tumors are biologically very diverse, which makes it harder to develop effective targeted therapies or immunotherapies that work broadly across patients,” said Jason Stevenson, MD, MSCR, commenting on the lower improvements seen with some cancers.

“In addition, children whose solid tumors are refractory to upfront treatment or relapse often have fewer effective treatment options available,” said the lead author of the study.

Stevenson, a pediatric hematologist/oncologist at Children’s Healthcare of Atlanta, and colleagues reported the results of the study in the journal Cancer.

Approximately 15,000 new cases of pediatric cancer occur each year. Earlier research by members of the study team found that while survival rates have pushed past 80% that cancer remains a leading cause of death in children and adolescents, the incidence of pediatric cancer has also increased.

The new study provides updated data on survival patterns and gaps in improvement across demographic subgroups and disease types for the purpose of informing clinical practice, research priorities and policy efforts, the authors wrote.

The researchers analyzed relative survival among 272,279 cancer diagnoses in children and adolescents up to 19 years old reported through the National Program of Cancer Registries (NPCR) survival dataset from 2001 to 2021.

The new research focused on relative survival, which estimates the survival likelihood of children with cancer compared with children who do not have cancer. “It helps isolate the effect of cancer itself rather than deaths from unrelated causes, so that you can know the true impact of cancer on survival,” Stevenson told Medscape Medical News.

Demographics Drive Disparities

Overall, 5-year relative survival increased from 83% from 2001 to 2011 to 86.8% from 2012 to 2021. Overall 10-year relative survival, which was not separated out by decade, was 82.3% for the 20-year study period vs 84.7% for the 5-year survival.

Relative survival at both 5 and 10 years was higher for females: 85.6% vs 83.9% for males at 5 years and 83.4% vs 81.3% at 10 years. Both sexes demonstrated improvements in 5-year relative survival from 2001-2011 to 2012-2021, increasing 3.4% for females and 4.1% for males. Five-year relative survival among females for the 2012-2021 study period still exceeded males: 87.5% vs 86.2%.

The study found similar trends in 5- and 10-year relative survival spread across three different age groups: infants up to 1 year, children 10-14 years, and adolescents 15-19 years. Infants had the lowest relative survival in both measures: 80.7% at 5 years and 79.2% at 10 years. Adolescents had the highest: 85.8% and 83.1%, respectively.

Relative survival was worse for Black patients than for White patients: 79.2% at 5 years and 76.3% at 10 years vs 86.3% and 84%. Five-year survival improved for all studied ethnic/racial categories — White, Black, non-Hispanic Asian or Pacific Islander, and Hispanic — from decade to decade. 

The study found an association between survival and economic and geographic factors. Highest relative survival rates were found in the wealthiest 25% of counties and in the Northeast, although 5-year survival increased across all economic groups, regions and metropolitan and nonmetropolitan categories from decade to decade.

“These factors are closely interconnected and reflect broader social determinants of health,” Stevenson said. “Access to specialized care, health insurance, transportation, financial resources and social support programs can all affect treatment and long-term survival.”

Biological differences, which may contribute to some cancer types, do not fully explain the disparities, he said. “More research is needed to identify the underlying causes and, most importantly, the interventions that can reduce these gaps so that all children have an equal opportunity for the best possible outcomes.”

Differences Between Cancer Type

The study identified disparities in 5-year relative survival between specific cancer types: 84.7% for leukemias, 93.1% for lymphomas, and 75.7% for central nervous system (CNS) cancers. A wide disparity was shown between lymphoid leukemias and acute myeloid leukemia (AML), with 5-year survival of 89% and 66.2%, respectively. Five-year survival for AML improved 8.9% from 2001-2011 to 2012-2021, with a 1.5% difference between 5- and 10-year survival (66.2% and 64.7%).

Advances in precision medicine and immunotherapies have made acute lymphoblastic leukemia “one of the great success stories” in pediatric oncology, Stevenson said, and explained why AML survival, while it “has also improved substantially,” still lags in comparison.

“AML is often driven by genetic changes that make the disease more resistant to treatment and increase the risk of relapse,” he said. “In addition, the intensive therapies used to treat AML carry higher risks of serious infections and long-term heart complications, which also affect overall survival.”

Continued research into targeted therapies and less toxic treatments are needed, he said.

Among the most common lymphoma types, Hodgkin and non-Hodgkin, 5-year survival rates were 96.8% and 90.1%, respectively, with differences of 1.4% and 1.3% between 5- and 10-year survival for Hodgkin and non-Hodgkin disease. Five-year survival for Hodgkin lymphomas improved 2.6% from decade to decade and 6% for non-Hodgkin disease.

Five-year survival for specific CNS tumors ranged from 60.3% for unspecified neoplasms to 84.5% for astrocytoma, with the gap between 5- and 10-year relative survival ranging from 2.1% for astrocytoma to 8.6% for ependymoma. The decade-to-decade improvement in 5-year survival for all CNS and related neoplasms was 2.5%. 

The use of the NPCR data “provides one of the most comprehensive national pictures of childhood cancer survival available,” Stevenson said. However, a drawback is that the database does not include detailed information on individual treatments and tumor genetics and the county-level economic data the study used may not fully capture an individual family’s circumstances, he said.

Call for Continued Investment in Research

Ongoing investment in research will be essential to advance survival of pediatric cancer, Stevenson said. “We need to develop more effective therapies for cancers that have seen slower progress,” he said. “At the same time, improving access to high-quality care, health insurance and social support programs will be critical for reducing persistent disparities in outcomes.”

The study helps make the case for continued federal government spending on pediatric cancer research, Douglas Hawkins, MD, a hematologist/oncologist at Seattle Children’s and the University of Washington in Seattle and chair of the Children’s Oncology Group, said. “If we want to continue to push the 10-year survival rates higher, if we want to try to reduce the short- and long-term side effects of treatment, we’re going to need continued substantial and sustained federal investment in pediatric cancer research,” he said.

The study itself, he said, is “a good snapshot” of the state of pediatric cancer survival, but he questioned its focus on survival. “It gave us glimpses into areas, tumor types that really need our attention, where the survival rates are significantly lower than others,” he said.

He credited the investigators for going beyond the 5-year survival rates pediatric cancer studies traditionally focus on and called for future research to examine 10- and 20-year survival.

One limitation is that the study did not explore the full burden of treatment, Hawkins said.

“It doesn’t look at some of the long-term side effects of treatment, so it doesn’t capture whether people have developed secondary cancers or have developed heart disease or have had a stroke as a result of the treatment that was given to cure the cancer.”

Stevenson and Hawkins reported having no relevant financial relationships.

Richard Mark Kirkner is a medical journalist based in the Philadelphia area.