A Novel Approach to Determining Tumor Progression Using a Three-Site Pilot Clinical Trial of Spectroscopic MRI-Guided Radiation Dose Escalation in Glioblastoma
Karthik K. Ramesh,
Vicki Huang,
Jeffrey Rosenthal,
Eric A. Mellon,
Mohammed Goryawala,
Peter B. Barker,
Saumya S. Gurbani,
Anuradha G. Trivedi,
Alexander S. Giuffrida,
Eduard Schreibmann,
Hui Han,
Macarena de le Fuente,
Erin M. Dunbar,
Matthias Holdhoff,
Lawrence R. Kleinberg,
Hui-Kuo G. Shu,
Hyunsuk Shim,
Brent D. Weinberg
Affiliations
Karthik K. Ramesh
Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
Vicki Huang
Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
Jeffrey Rosenthal
Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
Eric A. Mellon
Department of Radiation Oncology, University of Miami, Miami, FL 45056, USA
Mohammed Goryawala
Department of Radiology, University of Miami, Miami, FL 45056, USA
Peter B. Barker
Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21218, USA
Saumya S. Gurbani
Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
Anuradha G. Trivedi
Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
Alexander S. Giuffrida
Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
Eduard Schreibmann
Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
Hui Han
Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Macarena de le Fuente
Department of Neurology, University of Miami, Miami, FL 45056, USA
Erin M. Dunbar
Department of Neuro-Oncology and Neurosurgery, Piedmont Atlanta Hospital, Atlanta, GA 30309, USA
Matthias Holdhoff
Department of Oncology, Johns Hopkins University, Baltimore, MD 21218, USA
Lawrence R. Kleinberg
Department of Radiation Oncology, Johns Hopkins University, Baltimore, MD 21218, USA
Hui-Kuo G. Shu
Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
Hyunsuk Shim
Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
Brent D. Weinberg
Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
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).
