Early intervention key to mitigate neurocognitive effects of pediatric cancer treatment
As cancer treatment options continue to improve, the growing number of childhood cancer survivors will require individualized strategies and risk assessment to help prevent and monitor neurocognitive late effects.
Estimates have shown that approximately one-third of all cancer survivors and approximately 40% or more of brain tumor survivors experience neurocognitive impairment brought on by both the disease and its treatments.
Healio spoke with experts in pediatric neuropsychology about best practices to prevent, monitor for and address neurocognitive late effects among those undergoing treatment for cancer as a follow-up to our article on the prevalence and assessment of such effects among childhood cancer survivors.
Neurocognitive impairment, especially when it develops during childhood, can limit educational attainment, including not getting into or graduating college; can reduce employability either to unemployment or to occupations with lower income; and can limit insurance access due to complications, according to Kevin R. Krull, PhD, faculty member and endowed chair in cancer survivorship in the departments of epidemiology and cancer control and psychology at St. Jude Children’s Research Hospital.
“Neurocognitive impairment can also increase risk for health complications,” Krull told Healio in an interview. “Many individuals with impairment have difficulty with memory, planning, organization and time management, all of which can influence diet choices and exercise schedules, and interfere with the ability to adhere to medical screening recommendations or medication schedules.”
Krull continued that this impact on health behavior and health care use can, in turn, further exacerbate neurocognitive impairment.
“Neurocognitive impairment has also been shown to interfere with social interactions, including finding a life partner, and makes it more difficult to keep up with the rapid information processing pace of group interactions,” he said. “One of the big concerns I have about neurocognitive impairment is its interference with the ability to develop independent lifestyles. If an adult survivor of childhood cancer cannot live independently and continues to depend on support from their parents, what happens when they outlive their parents or their parents’ ability to live independently?”
Detecting early signs
To prevent or mitigate neurocognitive decline among childhood cancer survivors, assessment of an individual patient’s risk and continued monitoring are key.
Initial predictions include taking into consideration the characteristics of the disease — particularly if the cancer affected the brain or treatments were targeted to the central nervous systems — along with age at diagnosis.
Karin S. Walsh, PsyD, pediatric neuropsychologist in the division of pediatric neuropsychology at Children's National Hospital, said that it is useful to think about these cases with a “biopsychosocial model,” by piecing together the biology of the tumor itself, the interventions used for treatment, and the environmental factors affecting survivor’s development such as a family’s access to resources and socioeconomic status.
“We take each case knowing there’s a certain level of risk related to these factors,” Walsh told Healio. “Younger children, especially those diagnosed at an age younger than 5 years, are a higher risk group. It doesn’t mean every case is going to look the same, but it does mean we’re paying attention to them more.”
Walsh added that some factors can’t be completely predicted, such as genetics and cognitive reserve.
“It’s really important to assess each child individually despite the fact that we have some general guidelines for what might put a child at a higher risk than others,” she said.
Comorbidity is another factor to keep in mind, Krull said, because children who develop severe infections, who require numerous procedures under anesthesia, or who display adverse reactions such as seizures or stroke during cancer therapy tend to demonstrate worse outcomes.
Also, patients should be continually monitored so any early signs of neurocognitive effects can be detected earlier, when intervention might be more effective.
“In terms of individual detection, neuropsychological testing can identify the initial signs of
neurocognitive impairment prior to the end of cancer therapy,” Krull said. “These include slowed processing speed and variable attention. These initial problems predate academic problems and often evolve into problems with memory, learning and more complex skills such as planning. In general, the earlier the intervention the better the outcome.”
Many investigators are beginning to examine ways to prevent neurocognitive impairment by adjusting anticancer treatment regimens, Krull said.
“This starts with the oncologists who are now focused on lowering treatment intensity to improve outcome while maintaining high survival rates,” he said.
A report by Nicholas S. Phillips, MD, PhD, and colleagues, published this year in the Journal of Clinical Oncology as part of a special issues on neurocognitive outcomes in survivors of pediatric cancer, reviewed the growing body of evidence that shows both traditional cancer treatments and emerging therapies influence the risk for cancer-related neurocognitive impairments, including neurotoxicity observed with use of immunotherapy, adoptive cell therapy and immune checkpoint inhibitors.
“There are active attempts to employ drugs that reduce oxidative stress during cancer therapy to limit damage to healthy brain cells, though these are still somewhat experimental,” Krull said.
Because it is difficult to determine if or when a childhood cancer survivor may show signs of neurocognitive decline, prevention is as much about limiting the damage done during treatment as it is about continued best health practices.
“I cannot stress enough the importance of health behaviors,” Krull said.
In cases where a child is or may be at risk for neurocognitive impairment, Krull said that the best advice was to quickly engage them in prolonged cognitive stimulation and physical enrichment, including to:
- provide age-appropriate learning and enrichment (eg, reading, art, music);
- maintain healthy eating patterns and a healthy body weight;
- ensure regular physical exercise (both aerobic and resistance training);
- limit screen time and other sedentary behavior;
- maintain good sleep hygiene; and
- continue age-appropriate social interactions with positive peers and role models.
“These actions will help all children but are essential for children who are going to become cancer survivors,” he said. “Survivors of childhood cancer and cancer therapy have lower physiological and brain reserve, and they will be impacted to a greater degree by these health habits. This is why it is essential for survivors to develop and maintain healthy lifestyles.”
Krull also noted that long-term survivors of childhood cancer are at an elevated risk for chronic health conditions, including cardiac, respiratory, neurologic and endocrine morbidity. It is just as important to detect and treat these morbidities early to prevent their progression and limit their negative impact on typical development and aging, he said.
Best practices for these children involve monitoring them from treatment into young adulthood, Walsh said.
“Having health care teams that include neuropsychology has been something that impacts the patients and their families in very positive ways,” she said. “That team approach can assist with monitoring because there are different levels of assessment needed. There are tiers of monitoring, some of which happen in the clinic with the physician and others that need a comprehensive neuropsychologic assessment with a neuropsychologist. This is how we can collaborate with our physician colleagues to make their jobs easier and improve care for these children.”
- Hocking MC, et al. J Clin Oncol. 2021;doi:10.1200/JCO.20.02327.
- Jacola LM, et al. J Clin Oncol. 2021;doi:10.1200/JCO.20.02444.
- Phillips NS, et al. J Clin Oncol. 2021;doi:10.1200/JCO.20.02533.
For more information:
Kevin R. Krull, PhD, can be reached at firstname.lastname@example.org.
Karin S. Walsh, PsyD, can be reached at email@example.com.