Adaptive IMRT using a multiobjective evolutionary algorithm integrated with a diffusion-invasion model of glioblastoma.

We demonstrate a patient-specific method of adaptive IMRT treatment for glioblastoma using a multiobjective evolutionary algorithm (MOEA). The MOEA generates spatially optimized dose distributions using an iterative dialogue between the MOEA and a mathematical model of tumor cell proliferation, diffusion and response. Dose distributions optimized on a weekly basis using biological metrics have the potential to substantially improve and individualize treatment outcomes. Optimized dose distributions were generated using three different decision criteria for the tumor and compared with plans utilizing standard dose of 1.8 Gy/fraction to the CTV (T2-visible MRI region plus a 2.5 cm margin). The sets of optimal dose distributions generated using the MOEA approach the Pareto Front (the set of IMRT plans that delineate optimal tradeoffs amongst the clinical goals of tumor control and normal tissue sparing). MOEA optimized doses demonstrated superior performance as judged by three biological metrics according to simulated results. The predicted number of reproductively viable cells 12 weeks after treatment was found to be the best target objective for use in the MOEA.