Cognitive and neuroimaging outcomes in individuals with benign and low-grade brain tumours receiving radiotherapy: a protocol for a prospective cohort study

Abstract

Introduction: Radiation-induced cognitive decline (RICD) occurs in 50%-90% of adult patients 6 months post-treatment. In patients with low-grade and benign tumours with long expected survival, this is of paramount importance. Despite advances in radiation therapy (RT) treatment delivery, better understanding of structures important for RICD is necessary to improve cognitive outcomes. We hypothesise that RT may affect network topology and microstructural integrity on MRI prior to any gross anatomical or apparent cognitive changes. In this longitudinal cohort study, we aim to determine the effects of RT on brain structural and functional integrity and cognition.

Methods and analysis: This study will enroll patients with benign and low-grade brain tumours receiving partial brain radiotherapy. Patients will receive either hypofractionated (>2 Gy/fraction) or conventionally fractionated (1.8-2 Gy/fraction) RT. All participants will be followed for 12 months, with MRIs conducted pre-RT and 6-month and 12 month post-RT, along with a battery of neurocognitive tests and questionnaires. The study was initiated in late 2018 and will continue enrolling through 2024 with final follow-ups completing in 2025. The neurocognitive battery assesses visual and verbal memory, attention, executive function, processing speed and emotional cognition. MRI protocols incorporate diffusion tensor imaging and resting state fMRI to assess structural connectivity and functional connectivity, respectively. We will estimate the association between radiation dose, imaging metrics and cognitive outcomes.

Ethics and dissemination: This study has been approved by the Research Subjects Review Board at the University of Rochester (STUDY00001512: Cognitive changes in patients receiving partial brain radiation). All results will be published in peer-reviewed journals and at scientific conferences.

Trial registration number: ClinicalTrials.gov NCT04390906.

Keywords: magnetic resonance imaging; neurological oncology; radiation oncology; radiotherapy.

Figure 1

Study schema.

Figure 2

MRI data processing pipeline. AD, axial diffusivity; dMRI, diffusion MRI; DTI, diffusion tensor imaging; FA, fractional anisotropy; FC, functional connectivity; FEAT, FMRI Expert Analysis Tool; FIX, FMRIB’s ICA-based Xnoisefier; GTV, Gross Target Volume; MD, mean diffusivity; MELODIC, Multivariate Exploratory Linear Optimised Decomposition into Independent Components; RD, radial diffusivity; rs-fMRI, resting state functional MRI; RT, radiotherapy; SC, structural connectivity.

Figure 3

Representative images from participant with vestibular schwannoma. (A) RT dose map from RT structure set, mapped to CT image and scaled. (B) T1w structural image coregistered with CT image and RT dose map via affine transformation (yellow circle shows acoustic schwannoma). (C) T1w image with gross target volume (GTV, yellow circle) used to mask tumour prior to processing. (D) Subcortical and cortical structures obtained from brain parcellation, with vestibular schwannoma excluded (yellow arrow). RT, radiation therapy.

Figure 4

Representative functional connectivity correlation matrices. Matrices are computed using the Pearson correlation coefficient between every time course for all pairs of nodes. Matrices are thresholded at 0.5 and normalised. The average of all patient specific correlation matrices at baseline (A) and 6 months post-RT (B). The colour bar represents the normalised correlation coefficient between pairs of nodes. RT, radiation therapy.