Applying a Radiation Therapy Volume Analysis Pipeline to Determine the Utility of Spectroscopic MRI-Guided Adaptive Radiation Therapy for Glioblastoma.

Accurate radiation therapy (RT) targeting is crucial for glioblastoma treatment but may be challenging using clinical imaging alone due to the infiltrative nature of glioblastomas. Precise targeting by whole-brain spectroscopic MRI, which maps tumor metabolites including choline (Cho) and N-acetylaspartate (NAA), can quantify early treatment-induced molecular changes that other traditional modalities cannot measure. We developed a pipeline to determine how spectroscopic MRI changes during early RT are associated with patient outcomes to provide insight into the utility of adaptive RT planning. Data were obtained from a study (NCT03137888) where glioblastoma patients received high-dose RT guided by the pre-RT Cho/NAA twice normal (Cho/NAA ≥ 2x) volume, and received spectroscopic MRI scans pre- and mid-RT. Overlap statistics between pre- and mid-RT scans were used to quantify metabolic activity changes after two weeks of RT. Log-rank tests were used to quantify the relationship between imaging metrics and patient overall and progression-free survival (OS/PFS). Patients with lower Jaccard/Dice coefficients had longer PFS (p = 0.045 for both), and patients with lower Jaccard/Dice coefficients had higher OS trending towards significance (p = 0.060 for both). Cho/NAA ≥ 2x volumes changed significantly during early RT, putting healthy tissue at risk of irradiation, and warranting further study into using adaptive RT planning.

The Brain Imaging Collaboration Suite (BrICS): A Cloud Platform for Integrating Whole-Brain Spectroscopic MRI into the Radiation Therapy Planning Workflow.

Glioblastoma has poor prognosis with inevitable local recurrence despite aggressive treatment with surgery and chemoradiation. Radiation therapy (RT) is typically guided by contrast-enhanced T1-weighted magnetic resonance imaging (MRI) for defining the high-dose target and T2-weighted fluid-attenuation inversion recovery MRI for defining the moderate-dose target. There is an urgent need for improved imaging methods to better delineate tumors for focal RT. Spectroscopic MRI (sMRI) is a quantitative imaging technique that enables whole-brain analysis of endogenous metabolite levels, such as the ratio of choline-to-N-acetylaspartate. Previous work has shown that choline-to-N-acetylaspartate ratio accurately identifies tissue with high tumor burden beyond what is seen on standard imaging and can predict regions of metabolic abnormality that are at high risk for recurrence. To facilitate efficient clinical implementation of sMRI for RT planning, we developed the Brain Imaging Collaboration Suite (BrICS; https://brainimaging.emory.edu/brics-demo), a cloud platform that integrates sMRI with standard imaging and enables team members from multiple departments and institutions to work together in delineating RT targets. BrICS is being used in a multisite pilot study to assess feasibility and safety of dose-escalated RT based on metabolic abnormalities in patients with glioblastoma (Clinicaltrials.gov NCT03137888). The workflow of analyzing sMRI volumes and preparing RT plans is described. The pipeline achieved rapid turnaround time by enabling team members to perform their delegated tasks independently in BrICS when their clinical schedules allowed. To date, 18 patients have been treated using targets created in BrICS and no severe toxicities have been observed.