1. Introduction
tumor, Glioblastoma, aggressive cancer, BrICS-LIT, metabolic abnormalities
TUMOR, INFILTRATION, DISEASE, GLIOBLASTOMA, BRAIN TUMOR, AGGRESSIVE CANCER, BRAIN, TUMOR PROGRESSION, TUMOR RECURRENCE
Glioblastoma (GBM) is a fatal disease, with poor prognosis exacerbated by difficulty in assessing tumor extent with imaging. Spectroscopic MRI (sMRI) is a non-contrast imaging technique measuring endogenous metabolite levels of the brain that can serve as biomarkers for tumor extension. We completed a three-site study to assess survival benefits of GBM patients when treated with escalated radiation dose guided by metabolic abnormalities in sMRI. Escalated radiation led to complex post-treatment imaging, requiring unique approaches to discern tumor progression from radiation-related treatment effect through our quantitative imaging platform. The purpose of this study is to determine true tumor recurrence timepoints for patients in our dose-escalation multisite study using novel methodology and to report on median progression-free survival (PFS). Follow-up imaging for all 30 trial patients were collected, lesion volumes segmented and graphed, and imaging uploaded to our platform for visual interpretation. Eighteen months post-enrollment, the median PFS was 16.6 months with a median time to follow-up of 20.3 months. With this new treatment paradigm, incidence rate of tumor recurrence one year from treatment is 30% compared to 60–70% failure under standard care. Based on the delayed tumor progression and improved survival, a randomized phase II trial is under development (EAF211).Glioblastoma (GBM) is a highly aggressive cancer that originates in glial cells in the brain, with a very poor prognosis for every age group. The disease has a median survival of 15–16 months [Standard-of-care therapy for GBM patients is guided by a combination of T1-weighted contrast-enhanced MRI (T1w-CE) and T2-weighted fluid-attenuated inversion recovery MRI (FLAIR). T1w-CE indicates areas of high-grade tumor where gadolinium-based contrast agents can accumulate due to breakdown of the blood–brain barrier and is used to guide surgical resection. However, T1w-CE MRI usually underestimates the extent of tumor infiltration [We recently completed a multi-institutional, single-arm pilot clinical trial for newly-diagnosed GBM patients where brain regions with a Cho/NAA ≥ 2x normal were treated with an escalated radiation dose of 75 Gy [To address these challenges, we developed novel quantitative and visualization tools to track patients after initial treatment, minimize the effects of confounding treatment changes, pinpoint tumor recurrence timepoints, and perform PFS analysis. These tools use a combination of a quantitative imaging platform and structured reporting methods. The Brain Imaging Collaboration Suite Longitudinal Imaging Tracker (BrICS-LIT) is a custom-built web application for the purpose of longitudinal MRI imaging follow-up of brain tumor patients [