Neurocognitive outcomes in pediatric brain tumors after treatment with proton versus photon radiation: a systematic review and meta-analysis

World J Pediatr. 2023 Aug;19(8):727-740. doi: 10.1007/s12519-023-00726-6. Epub 2023 May 8.


Background: Advances in cancer treatments, particularly the development of radiation therapy, have led to improvements in survival outcomes in children with brain tumors. However, radiation therapy is associated with significant long-term neurocognitive morbidity. The present systematic review and meta-analysis aimed to compare the neurocognitive outcomes of children and adolescents with brain tumors treated with photon radiation (XRT) or proton therapy (PBRT).

Methods: A systematic search was conducted (PubMed, Embase, Cochrane, and Web of Science from inception until 02/01/2022) for studies comparing the neurocognitive outcomes of children and adolescents with brain tumors treated with XRT vs. PBRT. The pooled mean differences (expressed as Z scores) were calculated using a random effects method for those endpoints analyzed by a minimum of three studies.

Results: Totally 10 studies (n = 630 patients, average age range: 1-20 years) met the inclusion criteria. Patients who had received PBRT achieved significantly higher scores (difference in Z scores ranging from 0.29-0.75, all P < 0.05 and significant in sensitivity analyses) after treatment than those who had received XRT for most analyzed neurocognitive outcomes (i.e., intelligence quotient, verbal comprehension and perceptual reasoning indices, visual motor integration, and verbal memory). No robust significant differences (P > 0.05 in main analyses or sensitivity analyses) were found for nonverbal memory, verbal working memory and working memory index, processing speed index, or focused attention.

Conclusions: Pediatric brain tumor patients who receive PBRT achieve significantly higher scores on most neurocognitive outcomes than those who receive XRT. Larger studies with long-term follow-ups are needed to confirm these results.

Keywords: Brain health; Childhood cancer; Intelligence quotient; Radiotherapy.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Brain Neoplasms* / pathology
  • Brain Neoplasms* / radiotherapy
  • Child
  • Child, Preschool
  • Humans
  • Infant
  • Proton Therapy* / adverse effects
  • Proton Therapy* / methods
  • Protons
  • Young Adult


  • Protons