Spectroscopic MRI-Guided Radiation Therapy Planning in Glioblastoma Patients
Gliobastomas are the most common malignant brain tumor in adults with very poor survival. After surgical resection of visible tumor in standard imaging, treatment for glioblastoma involves radiation therapy with adjuvant and concurrent chemotherapy. With this protocol, the median overall survival is 15-16 months and progression free survival is 4-7 months in historical controls. In this trial, which opened in mid-2017, completed enrollment in mid-2019, and is closing soon, we sought to assess the efficacy and safety of escalating radiation dosage to the brain guided by metabolic abnormalities in brain tissue detected by spectroscopic MRI (sMRI). With sMRI, we previously found that regions of the brain where the ratio of metabolites Choline (Cho) to N-acetylaspartate (NAA) is highly correlative with tumor burden [1]. Often, sMRI can identify Cho/NAA abnormalities that standard clinical imaging like T1w-CE and T2/FLAIR fail to detect, which we believe leads to undertreatment of infiltrating tumor. To that end, in this trial we sought to irradiate regions of the brain with residual enhancing tumor and where the Cho/NAA ratio was greater than 2 times that in normal appearing white matter (NAWM) with 75 Gy of radiation, as well as 60 Gy for the resection cavity and 50.1 Gy for for FLAIR hyperintense regions (Figure 1B). As indicated in Figure 1A, sMRI detects much larger regions of infiltrating tumor that are otherwise not visible in standard CE-T1w MRI [2].
Through this treatment regimen, over one year after completing enrollment, we achieved a median overall survival of 23.0 months and a median progression free survival of 16.6 months (Figure 2) [2]. With these promising results with this cohort of 30 patients, a consortium trial with a larger patient population is in the process of starting.
[1] Cordova JS, Shu HK, Liang Z, et al. Whole-brain spectroscopic MRI biomarkers identify infiltrating margins in glioblastoma patients. Neuro Oncol. 2016; 18(8):1180-1189.
[2] Ramesh K, Mellon EA, Gurbani SS, et al., A multi-institutional pilot clinical trial of spectroscopic MRI-guided radiation dose escalation for newly diagnosed glioblastoma, Neuro-Oncology Advances, Volume 4, Issue 1, January-December 2022, vdac006, https://doi.org/10.1093/noajnl/vdac006