Monday, September 4, 2017

Temporally-Feathered Intensity Modulated Radiation Therapy: A technique to reduce normal tissue toxicity

Temporally-Feathered Intensity Modulated Radiation Therapy: A technique to reduce normal tissue toxicity

J. C. L. AlfonsoS. ParsaiN. JoshiA. GodleyS. A. KoyfmanJ. J. CaudellC. D. FullerH. EnderlingJacob Scott

Abstract

Purpose/Objective: We introduce a novel strategy of radiation therapy planning using canonical radiobiology principles and leveraging time to further decrease normal tissue complication probability (NTCP). Temporally feathered radiation therapy (TFRT) is presented as a strategy to reduce radiation-induced toxicity, and is compared with conventionally fractionated radiotherapy an in silico model of normal tissue radiation response. Material/Methods: As a first choice to compare conventional and temporally feathered plans, we consider the biologically equivalent dose (BED), which is the most common model used to compare different fractionation schemes in radiotherapy. We formulated a mathematical model to simulate normal tissue radiation-induced damage and recovery induced by different fractionation regimens. This model considers tissue recovery as a dynamic process rather than a static probability. Radiation response is determined by the Linear-Quadratic (LQ) model, which is widely used in radiobiology. Results: TFRT is shown to be beneficial in reducing radiation-induced toxicity to normal tissues compared to conventional treatment schedules. BED is not suitable to evaluate the success potential of TFRT because of its static nature in time, the proposed dynamical NTCP model however, demonstrates that there exists a window of opportunity for temporally feathering organs at risk whereby toxicity can be reduced without affecting tumor dosing. The high and low fractional doses delivered by temporally feathered plans to organs at risk allow increased damage recovery despite higher total doses compared to standard plans. The clinical benefit of temporally feathered plans not only depends on the combination of fractional doses considered, but also on the organ-specific recovery rate of radiation damage. In particular, we found that when comparing temporally feathered and standard plans, for each recovery rate a certain range of standard fractional doses exists in which TFRT reduces toxicity. Although the potential benefit of TFRT over conventionally fractionated radiotherapy is always higher in those ranges, there exists an optimal standard fractional dose in which toxicity induced by the temporally feathered plan is minimum. Conclusions: Our novel TFRT methodology opens a yet unexplored avenue for planning optimization in radiotherapy. Application of this technique to carefully selected cases will not only potentially allow reduction in normal tissue toxicity, but also allow dose escalation to the tumor thereby enhancing the therapeutic ratio.

http://www.biorxiv.org/content/early/2017/09/03/184044