Abstract

Abstract Background 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. Methods This prospective multicentre observational trial recruited patients with newly diagnosed GBM aged ≥65 planned for cranial radiotherapy. Baseline MRI scans were analyzed 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). Results 126 patients enrolled: mean age 72 years (range 65-83). 77% had debulking surgery. 79% received radiotherapy with concurrent TMZ, and 21% received palliative radiotherapy alone. The 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 = .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 the risk of non-attendance (OR 1.35, 95% CI 1.01 to 1.80, P = .042). Cox regression models showed baseline CSF:TIV was associated with worsened OS (HR 1.41, 95% CI 1.19 to 1.66, P < .001). Conclusions This study provides evidence to support the use of an imaging biomarker to help assess the risk:benefit ratio for radiotherapy.

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