SU-E-T-03: Justification and Feasibility of Neural Stem Cell Sparing in Whole Brain Irradiation Using VMAT.

PURPOSE To determine the impact of radiation on neural stem cells and examine the feasibility of neural stem cell sparing using volumetric modulated arc therapy (VMAT) for whole brain irradiation. METHODS Murine neural stem cells were harvested from the sub-ventricular zone (SVZ), cultured and assessed for radio-sensitivity and differentiation potential in response to radiation (0-6Gy). Clonogenic survival of these cells was compared to that of tumor cells derived from the murine PTEN-/-/Kras+ spontaneous brain tumor model. The differentiation potential of neural stem cells surviving irradiation was examined by allowing the cells to differentiate for five days and analyzing cell types. In order to address the feasibility of neural stem cell sparing, a typical 3D whole brain treatment was compared to VMAT, in which the neural stem cell compartment, designated and contoured as the lateral ventricles with a 3-5mm margin, was spared. Whole brain dose coverage was maintained similarly to conventional 3D treatment, while minimizing the dose to the stem cell compartment. RESULTS Neural stem cells are significantly more radio-sensitive than their tumor counterparts (2Gy, p=0.018), and the neuronal differentiation capacity of stem cells that survive radiation treatment is markedly diminished. Compared to conventional 3D treatment, VMAT reduces radiation dose to the stem cell SVZ compartment while maintaining adequate coverage of the whole brain. CONCLUSIONS Radiation-induced cognitive decline from whole brain irradiation is of particular clinical relevance. Cognitive functions are strongly influenced by the activity of neural stem cells, thus stem cell sparing may help mitigate radiation-induced cognitive decline. To our knowledge, this is the first study to confirm that radiation induces impaired neuronal differentiation at clinically relevant doses, and that improved stem cell sparing of the lateral ventricles (SVZ) is feasible using VMAT. Thus our studies confirm that VMAT should be examined further for clinical relevance in whole brain irradiation.