TU-F-BRF-08: Intensity Modulation Expanded to Spatio-Temporal Space; IMRT Combined with Optimal Fractionation Schedule




Past efforts to improve the therapeutic ratio have focused on a spatial approach where highly conformal radiation dose is given to tumors while minimizing dose to normal tissues, e.g., IMRT, VMAT, and IGRT. However, the fractionation schedule, i.e., a temporal approach to radiotherapy, has been largely overlooked so far in maximizing the therapeutic ratio. We establish a rigorous mathematical spatio-temporal approach to systematically investigate the feasibility and potential benefits of simultaneously optimizing radiation dose distribution in space and time.


Stochastic control formalism is constructed to maximize the average tumor BED by choosing an optimal radiation dose distribution for an optimal number of fractions subject to normal tissue BED constraints. Three separate simulations are run on two groups of phantom cases; 5 cases with prostate cancer and 5 cases with head-and-neck cancer. (1) Conventional IMRT with 70Gy/35fx for head-and-neck, and 81Gy/45fx for prostate, (2) IMRT is done independently from the fractionation schedule optimization (S-model), (3) integrated spatio-temporal approach (I-model) where radiation intensities are simultaneously optimized for the first time ever in space and time. Final tumor BEDs from the three trials are compared in prostate and head-and-neck cases.


Numerical simulations show that final tumor BED from I-model is 20–90% larger than conventional IMRT, and 20-50% larger than S-model for head-and-neck cancer with α/β=10 and Tdouble=2–50 days. Final tumor BED from I-model is also 90–140% larger than conventional IMRT, and 20–30% larger than S-model for prostate cancer with α/β=2 and Tdouble=5–80 days.


Our spatio-temporal optimization of radiotherapy allows an expansion of search space for the optimal treatment plans to include the temporal distribution of radiation dose in addition to the spatial distribution. Such spatio-temporal approach shows great potential to improve the therapeutic ratio, particularly with fast growing, aggressive tumors with short doubling time and/or low α/β.