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

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.

Fig. 1.

Composite doses received by brain structures, stratified by radiation modality. Medians are shown with a thick horizontal line, and means are shown with a closed circle. The boxplots represent first and third quartiles (IQR), whiskers denote values 1.5 × IQR away from the first and third quartiles, and outliers are shown with open circles. Abbreviations: PRI = perceptual reasoning index; VCI = verbal comprehension index; WMI = working memory index.

Fig. 2.

Modeled (estimated) cognitive index values at 3 years postradiation (y-axis), based on dose (Gy, x-axis) to brain structures most associated with cognition. Estimated cognitive scores (colored lines) are stratified by the presence or absence of posterior fossa syndrome. Overlaid on the graphs is a scatter plot of delivered dose to each individual patient and their actual test score values. By inspection, one can see that the filled circles predominate the left side of the x-axis, reflecting that patients who had proton therapy had less dose to brain structures overall. Abbreviation: RT = radiation therapy.