P18.28.A LONGITUDINAL TESTING OF COGNITIVE FUNCTION IN GRADE 2 AND 3 IDH MUTATED DIFFUSE GLIOMA: EFFECT OF MEAN BRAIN DOSE IN PHOTON RADIOTHERAPY
Authors: Jaspers J , Méndez Romero A , El Yaakoubi A , Nout R , van den Bent M , Satoer D 
Published: October 2024

Abstract

BACKGROUND
Postoperative radiotherapy and chemotherapy improve progression free survival and overall survival in diffuse glioma. However, postoperative radiotherapy has been related to the development of delayed neurocognitive decline. Mean bran dose is currently used as one of the dosimetry parameters to select patients for proton therapy in the Netherlands. It is unknown whether this parameter is related to neurocognitive outcome. We investigated whether mean brain dose is related to neurocognitive decline in patients with grade 2 and 3 IDH mutated glioma treated with photon radiotherapy.

MATERIAL AND METHODS
Patients that underwent resection and postoperative radiotherapy for IDH mutated diffuse glioma, grades 2 or 3, underwent neurocognitive testing before surgery and after surgery in semiregular intervals until disease progression. Three tests were administerd: the HVLT measuring verbal learning, the TMT A/B measuring attention and visuomotor speed, and Letter Fluency (LF) measuring executive functioning and lexical access ability. From these tests, five test scores were normalized using population data: the HVLT imprinting, HVLT delayed recall condition, Trail Making Test A, Trail Making Test B and Letter Fluency. Patients were considered dropped out of neurocognitive testing if no test results were available 12 months preceding disease progression or end of follow-up. In order to estimate the effect of covariates on test performance, two random effects models were generated for each test variable: one with time from surgery as a dependent covariate, and one with WHO grade, clinical target volume (CTV), and mean brain dose as covariates. Survival statistics were computed for overall survival and disease free survival. Additionally, survival statistics were computed for “dropout-free survival” as a metric for testing compliance.

RESULTS
Between 10-2013 and 12-2022, 49 patients underwent neurocognitive testing. Tumor grade was grade 2 in 36 patients (73%). All grade 2 patients were treated to a dose of 50.4 Gy in 28 fractions and all grade 3 patients were treated to a dose of 59.4 in 33 fractions. Mean dose to brain minus CTV was 17.8 Gy (16.1 - 19.4). Median follow-up in patients free from disease progression was 5.8 years (range 1.1 - 20.8). A total of 209 neurocognitive tests were completed; a median of 4 per patient (range 1-9). Freedom from dropout during the first five years of follow up was 88% (95% CI 0.79- 0.98). For each of the five tests, the estimated coefficient for the effect for time was not significant from zero (p &gt; 0.34), indicating patients did not decline over time. A negative effect of mean brain dose was found for four out of five tests (p &lt; 0.02). There was no effect of tumor grade (p &gt; 0.2).

CONCLUSION
In this study, no effect of time on neurocognitive outcomes was found. An inverse relationship was observed between mean brain dose and test results, irrespective of grade.