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.

Inclusion Criteria:

- Patients with newly diagnosed with high grade glioma (grade 3 or 4) having completed
surgery.

- Patients must be ≥ 18 and ≤ 70 years of age;

- WHO/ECOG Performance Status of 2 or less.

- MRI of the brain as delineated above.

- Patients must sign a study-specific informed consent prior to study entry.

Exclusion Criteria:

- Evidence of brainstem involvement on radiographs;

- Evidence of oligodendroglioma histology.

- Evidence of progressive disease at the time of study entry;

- Evidence of extracranial distant metastatic disease;

- Prior cranial irradiation;

- Patients may not be entered on other studies that have progression free, disease
free, or overall survival as a primary endpoint;

- Patients with synchronous or prior malignancy, other than non-melanomatous skin
cancer unless disease free greater than 3 years;

- Pregnant women are ineligible as treatment involves unforeseeable risks to the
participant and to the embryo or fetus; patients with childbearing potential must
practice appropriate contraception.