A system to provide enhanced computational efficiency in determining dose in a media of varying density from a high-energy radiation-beam for radiation treatment, program product, and related methods are provided. The system can include a radiation treatment planning computer and radiation treatment planning program product adapted to enhance optimization of a radiation treatment plan for delivering radiation to a complex medium defining a patient volume. The program product provides functions including those for predetermining a delivery machine-dependent representation of radiation dose for different electron densities selected over a representative range, predetermining a depth-dependent representation of central axis properties of a pencil beam passing through a complex medium, and determining with constant time computational complexity, radiation dose for each of a plurality of points of interest in a heterogeneous medium having a complex spatial distribution of heterogeneous electron densities by applying the predetermined machine-dependent and depth-dependent representations.