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July 13, 2021
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Young children with brain tumors may experience cognitive difficulty before treatment

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Young children with brain tumors experienced cognitive difficulties prior to adjuvant treatment, with those of a younger age at diagnosis and lower socioeconomic status at greatest risk, according to a study in Journal of Clinical Oncology.

In addition, changes in cognitive function as children aged were associated with tumor location and surgical factors as opposed to treatment exposure, results of the phase 2 multi-institutional study showed.

Heather M. Conklin, PhD, researcher in the department of psychology at St. Jude Children’s Research Hospital

“It is well-established that children treated for brain tumors are at risk for cognitive problems that negatively impact their quality of life,” Heather M. Conklin, PhD, researcher in the department of psychology at St. Jude Children’s Research Hospital, told Healio. “Young children are at particular cognitive risk due to vulnerability of a developing brain and missed normative social and learning experiences due to treatment requirements. Thus far, there are few studies that investigated neurocognitive trajectories for very young children treated for brain tumors, with the few available studies inconsistent in their findings.”

Conklin and colleagues sought to determine predictors for cognitive outcomes among a cohort of 139 children (mean age at diagnosis, 1.7 years; 59% male; 74.8% white) who received chemotherapy with or without focal proton or photon radiation therapy for central nervous system tumors during infancy between November 2007 and May 2017.

Researchers performed cognitive assessments at baseline, 6 months, 1 year and annually thereafter for up to 5 years. Neurocognitive testing consisted of assessment of intellectual functioning, parent ratings of executive functioning and emotional and behavioral functioning, and socioeconomic status.

Median follow-up was 26.8 months.

According to study results, mean baseline IQ was 89.88 (standard deviation, 18.22), with IQ significantly below age expectations (estimated intercept, 90.85; standard error, 1.37; P < .001).

Children of higher socioeconomic status had higher IQ scores at baseline (P = .004), whereas researchers reported “marginal evidence” that children aged younger at diagnosis had lower baseline IQ scores.

Results of random coefficients models showed an estimated intercept for Behavior Rating Inventory of Executive Functioning-Preschool Version (BRIEF-P) working memory of 57.26 (standard error, 1.33), which was lower than age expectations (P < .001). Estimated Bailey-III Adaptive Behavior Composite intercept also was significantly below normative expectations (0.78; standard error, 0.1; P < .001).

Children with supratentorial tumor location requiring cerebrospinal fluid diversion appeared at greatest risk for cognitive difficulties. However, researchers observed no association of treatment exposure with differences in cognitive outcomes.

“[Although] these findings need to be replicated in larger samples and followed for longer periods of time, there is some indication that the pattern of neurocognitive outcomes for young children treated for brain tumors is different than for older children. This finding may relate to increased vulnerability to tumor mass effect and surgery and/or greater neuroplasticity facilitating recovery,” Conklin said. “We now have plans to look at additional cognitive risk factors in this population, incorporate genetic and neuroimaging methods in future studies and develop cognitive interventions specifically tailored for younger children.”

These findings should be interpreted in a circumspect manner, as follow-up was only about 1 year after treatment completion and the deficits that occur within the domains of attention, working memory, processing speed and executive functioning emerge around 2 years after completion of treatment for pediatric brain tumors, according to an accompanying editorial by Stephen A. Sands, PsyD, researcher at Memorial Sloan Kettering Cancer Center.

“Although caution is warranted, the implications of these preliminary results may represent a turning point with regard to the timing of baseline assessments, perhaps providing a more complete understanding of the impact from the tumor, surgery and adjuvant therapies for those at highest risk, who could benefit from proactive, targeted interventions to improve survivorship,” Sands wrote.

For more information:

Heather M. Conklin, PhD, can be reached at St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Mail Stop 740, Memphis, TN 38105; email: heather.conklin@st.jude.org.

References:

Ali JS, et al. J Clin Oncol. 2021;doi:10.1200/JCO.20.01687.
Sands SA, et al. J Clin Oncol. 2021;doi:10.1200/JCO.20.01687.