A two-beam IMPT plan for brain tumor optimized based on criteria defined in terms of constant RBE of 1.1 (squares) and in terms of variable RBE computed using a model published by Wilkens, et al. (triangles). After optimization, both dose distributions were converted to variable RBE-weighted dose for comparison. The dose to the gross tumor volume (GTV) is more homogeneous for variable RBE-weighted optimization but lower to normal tissues to varying degrees. Notably, the dose in a 5 mm shell surrounding the GTV is reduced substantially. (Unpublished, Courtesy of Cao, University of Houston.)