Stem Cell Radiotherapy and Temozolomide for Newly Diagnosed High-grade Glioma

Even after optimal standard treatment, the outcome for patients suffering from glioblastoma (GB) is currently dismal, and temozolomide adds a modest survival benefit at high monetary cost and is accompanied by considerable toxicity. A possible explanation for the failure of radiotherapy to cure GB is the observation that glioma cells migrate widely into healthy bilateral brain tissue from one or more foci of origin. These isolated cells are not detected by current radiological techniques or even imaging and therefore usually not included into the target volume during radiotherapy. In this present study the investigators would like to test the hypothesis that the dose prescribed to the normal tissue stem cell niche in the adult brain will influence the effectiveness of radiotherapy for patients suffering from HGG/GB as these niches may serve as a harbor for radioresistant glioma stem cells, which are the only cells in a HGG believed to able to repopulate a tumor. The hypothesis is based on previous reports showing that adult normal tissue stem cells reside in the lateral periventricular regions of the lateral ventricles and animal studies reporting that transformation of normal tissues stem cells but not differentiated cells lead to tumor formation. This unique anatomical pattern of the brain that clearly separates stem cell niches as a potential pool of cancer stem cell (CSC's) from differentiated tissue make this an ideal model system to study the impact of radiation dose given to these stem cell niches. Therefore, prospective, randomized clinical trials are needed to address the efficacy and toxicity of including the CSC-containing subventricular region as additional target volumes into treatment plans for patients suffering from HGG/GB. This intervention could dramatically improve the outcomes of patients suffering from progressive, relapsing disease despite our best efforts currently.