A treatment planning system for a radiotherapy apparatus comprises a processor that receives an input data set comprising: a dose distribution within a volume to be irradiated that is to be achieved by the radiotherapy apparatus； a three dimensional volume image that characterises tissue types within the volume； and a set of process parameters which characterise a delivery process of radiotherapy. The system outputs a treatment plan to deliver the dose distribution when implemented by the delivery process, by optimising a function that includes at least one part representing a time-dependent response of the tissue types to an applied radiation dose. The input data set may further comprise a number of treatment fractions over which the dose distribution is to be delivered and the processor arranged to assign fractional parts of the dose distribution to successive treatment fractions, taking into account time and dose dependent characteristics of the tissue types in the volume image. The three-dimensional volume image may characterise the tissue types according to at least their local microenvironment. The at least one part representing a time-dependent response of the tissue types may represent at least one of a cell repair model and a tumour diffusion model.
