Neurocognitive impairment in childhood cancer survivors stems from both disease, treatment

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Cancer in children

September 14, 2021

5 minutes reading

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Healio interviews

Hocking, Krull and Williams report no relevant financial disclosures.


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Childhood cancer survivors are later at risk for neurocognitive decline associated with the disease and treatment, a complication that may become more common as cancer treatments improve and more survivors reach adulthood.

Research has shown that apparent neurocognitive impairments are possible after treatment targeting the cranial nervous system, such as exposure to cranial irradiation, intrathecal chemotherapy and neurosurgery.

However, neurocognitive impairment has also been observed in children who do not receive such therapies.

In either case, a neurocognitive impairment may not develop immediately after therapy, but at later stages of survival.

“Neurocognitive and neurological late effects are very important issues for a large number of our survivors and can have some very real consequences,” Matthew C. Hocking, PhD, child psychologist in the oncology department at the Philadelphia Children’s Hospital, Healio told an interviewer. “For example, adolescent and young adult survivors of childhood brain tumors are at risk of having few friends and attending college less, having full-time jobs and living independently.”

Hocking added that doctors can improve important aspects of quality of life by reducing the risk of these late effects and addressing them when they first develop.


The prevalence of neurocognitive impairment in cancer survivors varies by diagnosis, treatment, and time since treatment. Kevin R. Krull, PhD, faculty member and endowed chair in cancer survival in the departments of epidemiology and cancer control and psychology at St. Jude Children’s Research Hospital, Healio said.

At the onset of long-term survival, about 5 years after diagnosis, about 30% of cancer survivors and about 40% of survivors with brain tumors have significant neurocognitive impairment, according to Krull. In addition, about 55% of cancer survivors and about 70% of brain tumor survivors show symptoms of neurocognitive impairment during middle adulthood.

“This increase appears to be related to accelerated aging and accelerated accumulation of chronic health problems,” she said. “Advances in modern therapy now used at St. Jude Children’s Research Hospital appear to reduce the prevalence of early onset long-term survival disorders to between 25% and 35%, and we hope this lower rate maintained as these new survivors mature.”

Hocking added that, in addition to cancer type and treatment, age at diagnosis and treatment may influence the risk of neurocognitive impairment in survivors, whether immediately after treatment or later in life.

“Certain cancer treatments, especially cranial radiation therapy and intrathecal chemotherapy, carry a higher risk,” he said. “This is especially true for children who are diagnosed and treated at a younger age, because cancer therapies that target the brain affect future brain development. Since the two most common cancers in children – acute lymphoblastic leukemia and brain tumors – both involve factors “Many childhood cancer survivors are at risk for neurocognitive late effects. The types and severity of neurocognitive late effects generally depend on how all of these factors interact.”


Assessment of neurocognitive impairment or decline in cancer survivors is often completed with the use of comprehensive neuropsychological assessments.

Hocking said these assessments use norms-based, standardized tests to assess various aspects of cognitive functioning, including working memory, processing speed, executive function and attentional regulation.

“Historically, these assessments take a full day and are completed by neuropsychologists,” he said. “Because neuropsychologists are scarce, we haven’t been able to assess everyone who needs it. This is especially difficult because we often want to have a child serially evaluated over time to check for progressive deterioration and determine appropriate accommodation and services.”

To address some of these challenges, Hocking added that the field is now moving towards shorter assessments, in an effort to screen those at risk and determine who needs a more comprehensive assessment. In addition, automated assessments that do not necessarily require a fully trained neuropsychologist are also becoming more prominent.

“Here at the Children’s Hospital of Philadelphia, we have developed a new screening program and are now trying to assess every child who may experience cognitive changes as a result of their cancer,” Hocking said.

Connection with vulnerability

Annalynn Williams, PhD, A study recently conducted with co-author Krull and colleagues, published in the Journal of Clinical Oncology, focused on the link between frailty and neurocognitive decline in adult childhood cancer survivors.

Results of the study showed that both frail and prefrail childhood cancer survivors experienced greater declines in memory, attention and executive function – domains often associated with aging and dementia – compared to non-frail survivors.

Williams, of the Department of Epidemiology and Cancer Control at St. Jude Children’s Research Hospital, told Healio that these complications are often shown in older patients with breast cancer.

“However, in our study, the declines we found were large and among young adult survivors who experienced these declines decades earlier than their peers,” Williams said. “As a significant number of childhood and adolescent cancer survivors experience frailty, we wanted to understand whether these associations existed or are exacerbated in young adult survivors to identify a group at risk for intervention to preserve neurocognitive function. Vulnerability and neurocognitive decline can share similar underlying mechanisms and may respond to interventions designed to simultaneously improve physical and neurocognitive functioning.”

The number of different chemotherapeutic agents and radiation that survivors may be exposed to during treatment, either directly to the cranial nervous system or other parts of the body, can lead to systemic and organ-specific damage, Williams explains.

“In addition to frailty, our group has recently shown that chronic health problems, such as cardiopulmonary disease, are associated with neurocognitive impairment,” he said. “We hypothesize that the initial insult to their neurocognitive functioning by cancer treatment is exacerbated later in life by conditions such as vulnerability to neurocognitive decline earlier than if they had never had cancer.”

Addressing neurocognitive decline

As physicians continue to research the current and future prevalence of and associations with neurocognitive impairment in survivors, another hurdle is ensuring patients receive the care they need, either as preventive measures or interventions.

Hocking noted that there aren’t many “great options” for intervention right now, but the options that have been tested and shown improvements — including personalized cognitive rehabilitation therapies, automated interventions and physical activity interventions — may not be easily accessible.

“Access is probably the biggest problem in terms of survivors and families using these interventions,” Hocking said. “In general, these interventions are only available in large pediatric medical centers in the context of a research study. This really limits who can access it. Our field has the ability to determine the best evidence-based interventions that are effective and then disseminate them to health care providers in the community – and train them accordingly – so that they are accessible to those who need them.”

Because of its interactions with other conditions, such as frailty, ongoing monitoring of this population is critical.

“It is also important to participate in recommended surveillance for health problems at risk to limit contributions of new chronic health to neurocognitive decline,” Krull said.

Williams and Krull agreed that broad interventions targeting both physical and neurocognitive function, designed with childhood and adolescent cancer survivors, are needed.

“In the meantime, it’s important to advise survivors to avoid sedentary behavior and participate in mind-stimulating and social activities,” Krull said.


For more information:

Matthew C. Hocking, PhD, can be reached at

Kevin R. Krull, PhD, can be reached at

AnnaLynn M. Williams, PhD, can be reached at


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