Intensity-modulated radiation to spare neural stem cells in brain tumors: A computational platform for evaluation of physical and biological dose metrics

Abstract

Background: Neurocognitive effects following whole-brain and partial-brain irradiation can cause considerable morbidity. Sparing of neural stem cells (NSCs) is proposed as an avenue for reducing the long-term radiation-induced defects in learning, memory, and intelligence. We performed an analytical study to spare the NSC from partial-brain irradiation by intensity-modulated radiotherapy (IMRT). Objective: The aim of this study is to achieve maximal sparing of NSC during irradiation of brain tumors using biologically equivalent dose (BED) for all plans. The consequent clinical benefit will possibly be in terms of acute effects on stem cells and delayed neurologic sequelae to brain. A tool to modulate various physical and biological dose metrics has been used to study the optimization of radiation therapy for brain tumors with constraints imposed on total radiation to NSC. Materials and Methods: A total of 10 successive patients of grade III and IV gliomas of brain, who underwent total or near total excision of brain tumors, were included in the study. Patients underwent computed tomography and magnetic resonance imaging fusion for contouring. Computational codes used to analyze the efficacy of the plan are quality of coverage, homogeneity index, and conformity index. Wide range of radiosensitivity parameters were evaluated by using equivalent uniform dose and tumor control probability (TCP) to predict tumor control with and without sparing of NSC. Results: The physical and biological dose metrics were modulated by fitting standard deviation of 0.3% for all plans. The maximum NSC sparing was achieved in IMRT plans with constraints applied to local TCP. Similarly, for BED of plans with and without constraints, the estimated mean reduction in acute complications of NSC achieved was 12.23% (range, 4.27-28.33%). The estimated mean reduction in BED for late complications of late-reacting brain tissue is 14.69% (range, 7.39-33.56%).