A Prospective Trial of Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide for Newly Diagnosed Glioblastoma Multiforme
Radiation therapy (RT) is an integral component of the management of brain tumors, but
cognitive deficits following cranial irradiation are well documented. There is an
association between damage to neural progenitor cells (NPC) and neurocognitive dysfunction.
NPC are similarly known to play an important role in recovery from damage to the brain,
including radiation-induced damage. However NPC are extremely sensitive to radiation. In
spite of this information, current RT planning techniques do not limit the radiation dose to
the NPC containing regions. Recent human studies have demonstrated that it is possible to
use intensity modulated radiation therapy to reduce the radiation dose to NPC containing
regions during RT for brain tumors, without compromising coverage of the tumor. We
hypothesize that NPC-sparing RT will reduce neurocognitive decline following treatment for
brain tumors, without compromising tumor local control. However, there is conflicting data
regarding the role of NPC in the development of glioblastoma multiforme (GBM). Some studies
suggest that GBM are derived from NPC whereas others have associated NPC with improved tumor
control following therapy for GBM. Prior to evaluation of neurocognitive outcomes with
NPC-sparing RT, it is therefore imperative to evaluate whether NPC-sparing RT techniques
lead to increased LR in the spared NPC containing niches of the brain.
The proposed study is designed to evaluate LR in the spared regions of the brain following
NPC sparing RT in patients with newly diagnosed GBM. Our research will consist of 3 specific
aims: 1) Determine the LR rate at 1 year in the spared NPC containing niches in patients
treated with NPC sparing RT for GBM; 2) Quantify the extent of radiation dose sparing to the
NPC containing regions that is possible without compromising tumor coverage in patients with
GBM; 3) Determine if it is feasible to evaluate cognitive function prospectively in patients
undergoing NPC sparing RT for GBM.
The long term goal of this research is to establish whether NPC sparing RT techniques
improve neurocognitive outcomes compared to conventional RT for brain tumors. If the
proposed study demonstrates that NPC sparing RT is not associated with increased LR in the
spared regions of the brain compared to conventional RT, it will ideally serve as the
foundation for a future multi-institutional randomized controlled trial comparing
neurocognitive outcomes in patients treated with NPC-sparing RT versus conventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To estimate the local recurrence (LR) rate at 1 year in the spared neural progenitor cell (NPC) containing niches of the brain in patients treated with NPC sparing radiation therapy (RT) plus temozolomide for newly diagnosed glioblastoma multiforme (GBM).
Kristin Redmond, M.D.
The Johns Hopkins University School of Medicine
United States: Institutional Review Board
|The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231|