Abstract
The standard of care for glioblastoma is neurosurgical resection followed by radiation therapy (RT) and temozolomide (TMZ) chemotherapy. Previous RT with TMZ dose escalation attempts with RT doses up to 75 Gy targeted gadolinium contrast enhancing portions of tumor. These studies generated no significant benefits in recurrence or survival, but this may be because areas of gadolinium contrast enhancement only partially correlate with areas of future recurrence. Proton spectroscopic MRI (sMRI) measures endogenous metabolite levels without intravenous contrast agent. Elevated choline to N-acetylaspartate ratios (Cho/NAA) measured with whole brain sMRI mapping have significantly correlated with histological disease and, intriguingly, sMRI metabolic abnormalities predate disease recurrence. To enable RT dose escalation by sMRI in a multi-institutional clinical study setting, we specifically designed a cloud software platform to incorporate sMRI into the RT planning workflow. In order to test the sMRI workflow across institutions, a sMRI-guided dose escalation feasibility study is underway at three university hospitals (Emory, Johns Hopkins, and U. Miami). Eligible patients with glioblastoma after biopsy or surgical resection undergo MRI and sMRI within 14 days of start of therapy with TMZ and dose painted RT. Elevated Cho/NAA and residual contrast-enhancing lesions are targeted for boosted radiation to 75 Gy while the remaining tissue received standard-of-care therapy to 60 or 51 Gy in 30 fractions. Patients also receive a second sMRI scan during the third week of therapy to assess for early tumor response. Preliminary results are encouraging. In the first of three years of planned accrual, 11 patients (Emory 5, Miami 4, Hopkins 2) of a planned 30 have been treated within this trial with no observed serious adverse events. As this is a technical feasibility study with no control group, we plan for a future randomized cooperative group study with sMRI dose escalation versus standard of care.