Longitudinal analysis of cognitive function in patients treated with postoperative radiotherapy for grade 2 and 3 IDH mutant diffuse glioma.

Abstract

Postoperative radiotherapy and chemotherapy improve survival in IDH mutant diffuse glioma. We investigated whether neurocognitive function declines over time, and whether mean dose to the brain outside of CTV (mean brain dose) is related to neurocognitive function. Patients that underwent resection and postoperative radiotherapy for grade 2 or 3 IDH mutant diffuse glioma were tested using the Hopkins Verbal Learning Test, Letter Fluency and Trail Making Test before surgery and afterwards up until disease progression. Mixed effects models were fitted for each of three cognitive test scores, using time from surgery, mean brain dose, CTV volume, and tumor grade as fixed effects. Between 1-10-2013 and 31-12-2022, 49 patients underwent longitudinal neurocognitive testing. Average mean dose to brain minus CTV was 17.8 Gy (95 % CI 16.1 - 19.4). At the time of analysis, median follow-up in patients free from disease progression was 5.8 years (range 1.1 - 20.8). Attrition rate during the first five years of follow up was 14.1 %. There was no decline of test performance over time (p ≥ 0.526). However, there was a negative effect of increasing mean brain dose on TMT score A (-0.11, p = 0.008) and TMT score B (-0.13, p = 0.004). In this study, no effect of time after resection on test scores was found. Multivariable modelling indicates an negative relationship between mean brain dose and specific neurocognitive test scores, accounting for effects of tumor grade and CTV volume.