Social determinants of health: A forgotten risk factor for neurocognition in pediatric brain tumor survivors

Neurocognitive impairment is a known adverse effect following radiotherapy in pediatric and adult brain tumor patients. Neurocognitive decline can manifest across multiple domains, including memory, attention, processing speed, executive function, and especially for pediatric and young adult patients, intelligence quotient (IQ).¹ Children with neurocognitive deficits may fall behind on their learning trajectory relative to classmates, leading to inferior performance and achievement, inability to complete school and seek higher education, and failure to keep a full-time job and live independently.²

Data on neurocognitive decline following radiotherapy are widely known, such that physicians may delay or defer giving radiotherapy in selected brain tumor patients. Radiotherapy dose to the hippocampus and other radiosensitive brain substructures directly correlates with the risk of neurocognitive dysfunction.³ We know, however, that presence of a brain tumor itself, number of surgeries and surgical approach,^4,5 and use of systemic/intrathecal/intracystic chemotherapies also contribute to measurable neurocognitive deficits even before radiotherapy is administered.^6,7 Young age, hydrocephalus, antiepileptics, corticosteroids, hearing loss, metabolic/endocrine dysfunction, other medical comorbidities, and lower socioeconomic status (SES) also impact baseline and post-treatment neurocognitive function.

Quantifying the impact of individual variables on patient outcomes and toxicities is central to pediatric neuro-oncology and efforts to improve cure rates while minimizing late effects. In this issue, Mule and colleagues report that lower SES was significantly associated with poorer cognitive scores in 241 children treated with conformal photon radiotherapy (54-59.4 Gy) for ependymoma, low-grade glioma, and craniopharyngioma on a prospective trial. The authors demonstrate that lower SES predicted both baseline IQ and math scores and their change over time. Global economic hardship index score and measures of poverty in the patient’s neighborhood were the most consistent predictors of cognitive outcomes.⁸ After accounting for age and tumor location, pediatric patients with more favorable economic hardship index scores had higher baseline IQ and math scores and were more likely to preserve or experience significantly less decline in these scores over time than patients with lower SES (Figure 1).

This study highlights that we as a community are only beginning to understand the complex interplay between brain tumors, our treatments, and social determinants of health on neurocognition, survival, and future academic and vocational productivity. It is indisputable that patients with fewer opportunities and family/community support will struggle to achieve the same grades and accolades as more affluent students. Technological advances, like proton therapy, and dose reduction to normal organs may mitigate neurocognitive declines in brain tumor patients, but medical therapies will never abrogate poverty and other social determinants of health. Mule and colleagues refine our current understanding of SES and its impact on neurocognition after radiotherapy, but also highlight the need to prospectively collect data on and evaluate the interplay between radiotherapy dose, surgery, chemotherapy, and other often overlooked variables, such as SES, on both neurocognition and survival.

Key takeaways from this important work include: (1) all pediatric brain tumor patients treated with curative intent should regularly undergo neurocognitive assessments at baseline AND during follow-up as part of routine care (similar to other vital signs), (2) interventions during survivorship such as cognitive remediation therapy, maintaining a healthy lifestyle, and exercise can improve neurocognition,^9,10 and (3) clinicians must strive to minimize neurocognitive deficits through the selection of advanced treatment modalities, emphasize the importance of academic success during long-term follow-up, and recognize the importance of SES on survivorship.

Conflict of interest statement

M. Hall: Honorarium from Ion Beam Applications; research support from the Live Like Bella Pediatric Research Initiative, Florida Department of Health, Grants 8LA04 and 22L01. R. Kotecha: Honoraria from Accuray Inc., Elekta AB, ViewRay Inc., Novocure Inc., Elsevier Inc., Brainlab, Kazia Therapeutics, Castle Biosciences, Ion Beam Applications; institutional research funding from Medtronic Inc., Blue Earth Diagnostics Ltd., Novocure, Inc., GT Medical Technologies, AstraZeneca, Exelixis, ViewRay, Inc., Brainlab, Cantex Pharmaceuticals, Kazia Therapeutics, and Ion Beam Applications.