A common second course of radiation therapy for recurrent glioblastoma uses 35 Gy in 10 fractions to a small area defined by gadolinium enhancement on MRI. This is based in part on a recent cooperative group trial (RTOG 1205, NCT01730950) with concurrent bevacizumab resulting in very low toxicity and borderline progression free survival benefit. We hypothesize that radiation therapy would be more effective for recurrent glioblastoma when delivered to a larger area defined by spectroscopic MRI. The spectroscopic MRI can delineate occult microscopic disease not seen on clinical MRI. Our group was a partner in the multi-institutional spectroscopic MRI guided dose escalation pilot trial in the first line for glioblastoma (NCT03137888) showing safety and efficacy of planning radiation therapy based on spectroscopic MRI Choline to NAA (Cho:NAA) ratio maps. A local Cho:NAA ratio above 2 (Cho:NAA>2) is known to correlate with high local GBM burden on pathology. In this study, we will use the same technique to target radiation therapy to recurrent glioblastoma in a larger area of the brain harboring microscopic tumor. We will start with the conventional radiation dose of 35 Gy in 10 fractions to the larger area defined by the spectroscopic MRI. If this is safe and feasible, we will perform a dose escalation to 40 Gy in 10 fractions to areas of gadolinium enhancement and sMRI Cho:NAA>2 since existing data suggests that those areas harbor the highest risk of future progression. Use of proton radiotherapy to limit brain targeted outside of the treated regions and bevacizumab to prevent radiation toxicity are hypothesized to limit the side effects of this approach.
The purpose of this research is to find hidden cancer with an experimental magnetic resonance imaging (MRI) scan called spectroscopic magnetic resonance imaging (sMRI). That spectroscopic MRI scan will be used to increase the area of the brain receiving radiation and then the dose of radiation in attempt to kill more of the cancer. Proton radiotherapy and bevacizumab (Avastin) are used to minimize the possible side effects of this approach.