Baseline Total Brain Volume predicts for changes in quality of life and overall survival after cranial radiotherapy in older patients with a Glioblastoma (GBM). Results from the prospective BRITER study

Short-course partial brain radiotherapy +/- chemotherapy for older patients with GBM extends survival but there is no validated evidence for prediction of individual risk of acute radiotherapy related side effects. This prospective multicentre observational trial recruited patients with newly diagnosed GBM aged ≥ 65 planned for cranial radiotherapy. Baseline MRI scans were analysed for markers of brain resilience including relative total brain volume (ratio of cerebrospinal fluid (CSF) volume to total intracranial volume (TIV)) and their relationship to change in quality of life (QoL). 126 patients enrolled: mean age 72 years (range 65-83). 77% had debulking surgery. 79% received radiotherapy with concurrent TMZ, 21% received palliative radiotherapy alone. Median OS was 10.7 months. After accounting for age, sex, treatment and baseline MoCA score, there was a relationship between baseline CSF:TIV and change in QoL score at 8 weeks post treatment. For each unit point of increase in CSF:TIV, there was a corresponding decrease in QoL score of 1.72 (95% CI -3.24 to -0.19 p=0.027). 35 participants were too unwell to complete questionnaires or had died by the 8 week follow up visit. In this subgroup, post hoc logistic regression showed baseline CSF:TIV was related to risk of non-attendance (OR 1.35, 95% CI 1.01 to 1.80, p=0.042). Cox regression models showed baseline CSF:TIV was associated with worsened OS (HR 1.41, 95% CI 1.19 to 1.66, p<0.001). This study provides evidence to support the use of an imaging biomarker to help assess the risk:benefit ratio for radiotherapy.