Neural Stem Cell-Preserving External-Beam Radiotherapy of Central Nervous System Malignancies

Abstract

Recent discoveries have implicated neural stem cells (NSC) as the source of plasticity and repair in the mature mammalian brain. Treatment-induced NSC dysfunction may lead to observed toxicity. This study evaluates the feasibility of NSC-preserving external beam radiotherapy. A single computed tomography (CT) dataset depicting a right periventricular lesion was used in this study as this location reflects the most problematic geometric arrangement with respect to NSC preservation. Conventional and NSC preserving radiotherapy (RT) plans were generated for the same lesion using two clinical scenarios: cerebral metastatic disease and primary high-grade glioma. Disease-specific target volumes were used. Metastatic disease was conventionally treated with whole-brain radiotherapy (WBRT) to 3,750 cGy (15 fractions) followed by a single stereotactic radiosurgery (SRS) boost of 1,800 cGy to gross disease only. High-grade glioma was treated with conventional opposed lateral and anterior superior oblique beams to 4,600 cGy (23 fractions) followed by a 1,400 cGy (7 fractions) boost. NSC preservation was achieved in both scenarios with inverse-planned intensity modulated radiotherapy (IMRT). Cumulative dose reductions of 65% (metastatic disease) and 25% (high-grade glioma) to the total volume of the intracranial NSC compartments were achieved with NSC-preserving IMRT plans. The reduction of entry and exit dose to NSC niches located contralateral to the target contributed most to NSC preservation. Neural stem cells preservation with current external beam radiotherapy techniques is achievable in context of both metastatic brain disease and high-grade glioma, even when the target is located adjacent to a stem cell compartment. Further investigation with clinical trials is warranted to evaluate whether NSC preservation will result in reduced toxicity.