Proton Therapy Mediates Dose Reductions to Brain Structures Associated With Cognition in Children With Medulloblastoma

Authors

Julianna Sienna
Lisa S Kahalley
Donald Mabbott
David Grosshans
Anna Theresa Santiago
Arnold Dela Cruz Paulino
Thomas E Merchant
Gohar S Manzar
Hitesh Dama
David C Hodgson
Murali Chintagumpala
Mehmet Fatih Okcu
William E Whitehead
Normand Laperriere
Vijay Ramaswamy
Ute Bartels
Uri Tabori
Julie M Bennett
Anirban Das
Tim Craig
Derek S Tsang

Publication Date

5-1-2024

Journal

International Journal of Radiation Oncology, Biology, Physics

Abstract

Purpose: Emerging evidence suggests proton radiation therapy may offer cognitive sparing advantages over photon radiation therapy, yet dosimetry has not been compared previously. The purpose of this study was to examine dosimetric correlates of cognitive outcomes in children with medulloblastoma treated with proton versus photon radiation therapy.

Methods and materials: In this retrospective, bi-institutional study, dosimetric and cognitive data from 75 patients (39 photon and 36 proton) were analyzed. Doses to brain structures were compared between treatment modalities. Linear mixed-effects models were used to create models of global IQ and cognitive domain scores.

Results: The mean dose and dose to 40% of the brain (D40) were 2.7 and 4.1 Gy less among proton-treated patients compared with photon-treated patients (P = .03 and .007, respectively). Mean doses to the left and right hippocampi were 11.2 Gy lower among proton-treated patients (P < .001 for both). Mean doses to the left and right temporal lobes were 6.9 and 7.1 Gy lower with proton treatment, respectively (P < .001 for both). Models of cognition found statistically significant associations between higher mean brain dose and reduced verbal comprehension, increased right temporal lobe D40 with reduced perceptual reasoning, and greater left temporal mean dose with reduced working memory. Higher brain D40 was associated with reduced processing speed and global IQ scores.

Conclusions: Proton therapy reduces doses to normal brain structures compared with photon treatment. This leads to reduced cognitive decline after radiation therapy across multiple intellectual endpoints. Proton therapy should be offered to children receiving radiation for medulloblastoma.

Keywords

Child, Humans, Medulloblastoma, Proton Therapy, Protons, Retrospective Studies, Drug Tapering, Brain, Cognition, Cerebellar Neoplasms, Radiotherapy Dosage

DOI

10.1016/j.ijrobp.2023.11.035

PMID

38040059

PMCID

PMC11023754

PubMedCentral® Posted Date

5-1-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes