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Adult survivors of pediatric brain tumors face significant long-term cognitive impairment
Survivors of pediatric brain tumors appeared at risk for severe cognitive impairment in adulthood, according to findings from a study conducted by researchers from St. Jude Children’s Research Hospital.
Further, these impairments increased the risk for reduced educational attainment, unemployment and nonindependent living.
Tara M. Brinkman, PhD
Previous studies had indicated that treatment for pediatric brain tumors increased the risk for cognitive impairment in survivors; however, those studies followed survivors for a maximum of 10 years after therapy and had smaller populations. The only previous long-term study had self-reported patient data, according to study background.
“Adult survivors of pediatric brain tumors are at-risk for severe impairment in cognitive skills such as attention and memory several decades following treatment for their disease,” Tara M. Brinkman, PhD, assistant member of the faculty at St. Jude, told HemOnc Today. “Importantly, these cognitive deficits may not be recognized by survivors.
“These deficits do, however, have a negative impact on the ability of survivors to achieve developmentally expected milestones, including graduating from college, securing employment, and living independently,” she added.
The analysis included 224 patients from the St. Jude Lifetime Cohort who were aged at least 18 years (median age, 26 years; range, 19-53) and had survived at least 10 years (median time since diagnosis, 18 years; range, 11-42) from their childhood cancer diagnosis. Although researchers are currently still enrolling survivors randomly in groups of 50, the patients included in this study had a cutoff date of June 30, 2014.
Patients previously underwent craniospinal irradiation (n = 83), focal irradiation (n = 71) or no cranial irradiation (n = 63). Eighty-one patients also underwent shunt placement for hydrocephalus.
Forty patients had experienced seizures that were resolved, and 33 experienced unresolved seizures.
The survivors underwent neurocognitive testing. Researchers compared the prevalence of severe impairment — defined as impairment at least two standard deviations below the normative mean — across treatment groups.
Overall, 20% to 30% of survivors demonstrated severe impairment on performance-based measures of intellect, short- and long-term memory, mathematics and cognitive fluency. However, only 10% of survivors reported a significant adverse impact of cognitive skills on daily functioning, with the exception of working memory (21%; 95% CI, 16-26.8).
Results of multivariable models showed craniospinal irradiation increased the risk for severe impairment of intelligence (RR = 2.70; 95% CI, 1.37-5.34), memory (RR = 2.93; 95% CI, 1.69-5.08), executive function (1.74; 95% CI, 1.24-2.45) and academics (RR = 3.96; 95% CI, 1.94-8.08) compared with no radiation.
Researchers also observed an association between seizures and impaired academic performance (RR = 1.48; 95% CI, 1.02-2.14), attention (RR = 1.54; 95% CI, 1.12-2.13) and memory (RR = 1.44; 95% CI, 1.04-1.99).
Shunt placement to relieve hydrocephalus also appeared associated with impaired intelligence (RR = 1.78; 95% CI, 1.12-2.82) and memory (RR = 1.42; 95% CI, 1.03-1.95).
In multivariable models adjusted for current age and sex, survivors appeared more likely to not graduate college, be living with their parents or caretakers as adults, and be unemployed.
Researchers observed an approximate 40% increased risk for not graduating from college among survivors with impaired intellect (RR = 1.37; 95% CI, 1.23-1.52), academics (RR = 1.41; 95% CI, 1.26-1.57) or executive function (RR = 1.41; 95% CI, 1.2-1.66).
Survivors with severe impairment of intelligence (RR = 1.47; 95% CI, 1.22-1.76), academics (RR = 1.55; 95% CI, 1.29-1.86), memory (RR = 1.49; 95% CI, 1.23-1.8) or executive function (RR = 1.47; 95% CI, 1.18-1.83) had approximately a 50% increased risk for nonindependent living.
The risk for unemployment was twofold greater among survivors with impaired attention (RR = 2.37; 95% CI, 1.75-3.21), memory (RR = 1.87; 95% CI, 1.42-2.47) or executive function (RR = 2.17; 95% CI, 1.54-3.07).
The previous patient self-reports showed significantly less impact on the survivors’ quality of life than the current analysis. This may be because the patients are aware of their deficiencies and have learned ways to compensate for them, thus reporting a lower impact on their everyday lives, Brinkman said.
“The other hypothesis is that because many of our survivors are severely cognitively impaired, they may not be aware of the impact of the deficits on their daily lives,” Brinkman added.
These findings may help develop screening techniques to detect cognitive deficits in survivors, as well as to develop guidelines for follow-up care.
“Our results highlight the need for systematic monitoring of cognitive function during survivorship,” Brinkman told HemOnc Today. “We plan to continue to follow these patients to better understand cognitive aging in adult survivors of pediatric brain tumors. In addition, these results underscore the importance of identifying effective cognitive interventions with the potential to impact daily functioning.” – by Anthony SanFilippo
For more information:
Tara M. Brinkman, PhD, can be reached at tara.brinkman@stjude.org.
Disclosure: Brinkman reports no relevant financial disclosures. Other researchers report consultant/advisory roles with AstraZeneca, Celgene, the Department of Defense and SRA International; research funding from Genentech; and travel, accommodations or other expenses from IBA.
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This article by Brinkman and colleagues really illustrates the dilemma faced when treating children with brain tumors.
The brain continues to grow and develop well into early adulthood and interventions such as radiation therapy, extent of surgery and even chemotherapy during this period of growth have been considered a major risk for cognitive impairment.
The very interventions that can be lifesaving result in a life-long impact on employment, living independently and ability to succeed in school.
Although the impact of treatment clearly affects the very youngest of children, more needs to be done to study cognitive outcome in older children, adolescents and young adults.
In an effort to improve outcome, more study also needs to be done to develop treatment strategies that limit, if possible, the amount of radiation delivered to children, adolescents and young adults with brain tumors.