A prospective, longitudinal phase 2 study has found that family socioeconomic status (SES) is a strong predictor for neurocognitive outcomes in survivors after treatment for childhood brain tumors. Acute and chronic neurocognitive sequelae have been well described in these patients, but the risk of cognitive problems was thought to depend mostly on which treatments the patient received and other factors such as tumor type and age at diagnosis.

This research was led by investigators at St Jude Children’s Hospital in Memphis, Tennessee, and published in Neuro-Oncology.1 It suggests that the SES of families is a significant predictor of whether childhood brain tumor survivors will experience neurocognitive late effects up to a decade after their treatment.

Examining Cognitive Issues

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Children treated for brain tumors typically have a multitude of risk factors for cognitive issues. The tumor itself may cause symptoms, such as language or vision problems, that may have led to the initial diagnosis. Surgically resecting tumors comes with the risk of damaging cognitive function, and cranial radiation as well as certain types of chemotherapy are also associated with neurocognitive sequelae.

“The risk of cognitive issues is multifactorial as many previous studies have described, and treatment at a younger age was previously the most reliable risk factor for cognitive issues,” said Heather Conklin, PhD, of the department of psychology at St Jude and lead author of the work.

“What was most surprising about our study was that for some measures, the contribution of socioeconomic status was even greater than age at treatment, which has typically been [considered] the biggest risk factor,” added Dr Conklin.

The researchers followed the course of 248 children who were treated for ependymoma, low-grade glioma, or craniopharyngioma. The research team performed cognitive assessments of study participants frequently throughout 10 years of follow-up. Several metrics were assessed, including IQ, achievement in reading and math, attention, and adaptive function.

Each participant’s SES was assessed using the Barratt Simplified Measure of Social Status, which takes into account parental occupation, education, and marital status.

The Role of Socioeconomic Factors

High SES is known to be correlated to better cognitive performance in healthy children, and similarly, low SES is predictive of poorer cognitive performance. The study found significant associations between SES and IQ, academic achievement in reading and math, and adaptive function, with higher SES predicting better performance prior to radiation therapy in pediatric brain tumor survivors.

However, the research found that SES predicted change over time in 3 of these metrics after radiation therapy (IQ and achievement in reading and math), with higher SES being associated with less cognitive decline in these areas.

“What is most exciting is that what is driving these SES impacts are modifiable – whether it is reading books within the home or increasing advocacy for school services. We can’t modify age at diagnosis or sex, but we may be able to harness what’s good and protective about high SES and modify things for these [low SES] children,” said Dr Conklin.

The researchers are planning further analyses to attempt to pinpoint exactly which factors associated with high SES are related to better cognitive outcomes for childhood brain tumor survivors, with the hope that this will lead to designing interventions to improve cognitive outcomes for childhood brain tumor survivors who come from low SES families.

Future Directions

“Clinically we’ve been trying some of these things for years, but it will be much easier and more effective if we know what to target. We need to dismantle what is protective about high SES. For example, is it parental style, vocabulary use, literacy, advocacy with the child’s school? We assume these things are correlated with high SES and hence with better outcomes for childhood brain tumor survivors, but we need to find out what’s contributing the most,” said Dr Conklin.

Interventions targeting improvements based on SES are not the only strategies to improve cognitive outcomes in this patient population. Dr Conklin is also conducting an ongoing clinical trial (ClinicalTrials.gov identifier NCT03194906) with the dementia drug memantine to determine whether this can be used to change cognitive outcomes in childhood brain tumor survivors.

Other interventions currently under investigation for preventing cognitive changes in this patient group involve the diabetes drug metformin, which showed promising results in a pilot clinical trial last year.2


  1. Torres VA, Ashford JM, Wright E, et al. The impact of socioeconomic status (SES) on cognitive outcomes following radiotherapy for pediatric brain tumors: a prospective, longitudinal trial. Neuro Oncol. Published online February 5, 2021. doi:10.1093/neuonc/noab018
  2. Ayoub R, Ruddy RM, Cox E, et al. Assessment of cognitive and neural recovery in survivors of pediatric brain tumors in a pilot clinical trial using metformin. Nat Med. 2020;26(8):1285-1294. doi:10.1038/s41591-020-0985-2