Stem Cell Radiotherapy and Temozolomide for Newly Diagnosed High-grade Glioma
Stem Cell Radiotherapy and Temozolomide for Newly Diagnosed High-grade Glioma
There are preliminary studies that suggest that radiation therapy to areas of the brain
 containing cancer stem cells (in addition to the area where the tumor was surgically treated)
 may help patients with high-grade brain tumors live longer. The purpose of this study is to
 determine whether the addition of stem-cell radiation therapy to the standard chemoradiation
 will further improve the outcome. The investigators will collect information about the
 patient's clinical status, disease control, neurocognitive effects, and quality of life
 during follow-up in our department.

 The purpose of the study is to improve the overall survival patients with newly diagnosed
 malignant brain tumors treated with stem cell radiation therapy and chemotherapy. The
 investigators will also measure how patients treated with this novel method of radiation
 therapy do over time in terms of disease control, potential neurocognitive side effects,
 overall function, and quality of life.
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.