P13.18.B VOXEL-BASED ANALYSIS FOR ENDOCRINE AND COGNITIVE DAMAGE AFTER RADIOTHERAPY FOR PAEDIATRIC CNS TUMOURS
Authors: Aznar M , Davey A , Wilson L , Vasquez Osorio E , Vaughan K , Clayton P , Albutt L , van Herk M , Merchant T , McCabe M 
Published: October 2024

Abstract

BACKGROUND
Radiotherapy (RT) is a common treatment for paediatric brain tumours, but it can lead to long-lasting endocrine and cognitive sequalae. Voxel-based analysis (VBA) is a novel approach which can identify dose-sensitive regions in large cohorts of patients. Along with advanced RT approaches, such as Proton Beam Therapy, the identification of those regions could enable targeted dose reduction leading to fewer sequelae. We present the first VBA analysis on two independent cohorts of paediatric patients.

MATERIAL AND METHODS
VBA consists of two steps: 1) spatial normalisation of RT data (planning images and 3D dose distribution) onto a reference anatomy and 2) voxel-wise analysis of the correlation between dose deposition and outcomes. Here, data from 261 children (146 medulloblastoma patients in centre A, 115 patients with mixed diagnosis in centre B) was included. Treatment planning data (dose, MR+CT in centre A, CT only in centre B) were retrieved for all patients. The outcomes of interest were Growth Hormone Deficiency (GHD, presence/absence) and processing speed (PS, continuous slope derived from a linear mixed-effects model).The reference anatomy was selected within the cohort, as a single patient with a median brain volume. VBA was applied to identify a dose-sensitive region associated with each outcome (p value&lt;0.01). Then a multivariable analysis was performed including the mean dose delivered to this region and adjusting for age, risk status, hydrocephalus status/management, and chemotherapy.

RESULTS
For GHD, complete data was available for 146 patients from centre A and 115 patients from centre B. In each cohort, VBA identified a dose-sensitive region overlapping the hypothalamic-pituitary axis and the brainstem. Increase in GHD odds for every 1Gy to the identified region was calculated as: 13(2-27)% for centre A, with an inverse effect for age and 8(4-13)% for centre B with no other predictors.For PS, 139 patients in centre A were available for analysis. VBA identified a central frontal region from the medial frontal lobes to the hypothalamus where each 1Gy increase led to a -0.08(-0.20 - 0.04) PS change, with age and hydrocephalus management as contributing factors. Data from Centre B was too incomplete to allow for external validation. As alternative, sensitivity analysis was performed by repeating the VBA procedure on the cohort from centre A with two additional “reference anatomies”.The identified dose regions on each reference anatomy presented a high degree of concordance (&gt;75%), suggesting this result is robust to variations in spatial normalisation..

CONCLUSION
VBA identified a region (encompassing the hypothalamic-pituitary axis and brainstem) associated with increased risk of GHD. PS decline was linked to dose to a frontal region. Minimising dose to these identified regions could reduce the risk of cognitive and endocrine side-effects in future patients.