An Investigation of Spiked Hypofractionation for Treating Large Brain Tumors

Purpose:

Spiked Hypofractionation (SHF) aims to superpose a dose lattice over the 3D conventional dose distribution of a radiation treatment, yet at the same time shifting the dose lattice from one treatment fraction to another to create variable 3D dose distributions for the entire treatment course.

Methods SHF was tested by superimposing an array of 3D dose spikes within a target over the conventional 3D dose distribution for a dedicated hypofractionated brain radiosurgery system (Leksell Gamma Knife Icon, Elekta AB). This array of 3D dose spikes was produced by iteratively adding and optimizing a series of 4-mm shots placed inside the target, and then shifted and reoptimized from one treatment fraction to another. Using a generalized linear-quadratic model, voxel-by-voxel dose variations were tracked to compute biologically equivalent EQD2 for the full treatment course. The final EQD2 values for SHF were compared with the conventional hypofractionated treatments to determine the potential benefits of SHF.

Results: Compared to conventional fractionation, SHF significantly (p<0.01) elevated the mean target dose by approximately 34% while maintained target volume coverage, dose conformity and peripheral dose fall-off. Most interestingly, SHF drastically increased the equivalent EQD2 for the tumor (a/b =10 Gy) by 70% over conventional hypofractionated treatments of delivering 30 Gy in 5 fractions. Such an increase was more pronounced for the late-responding tumor types such as a/b =3 Gy vs 10 Gy, and for a higher number of fractions such as 5 versus 3 fractions.



Conclusion: SHF is a new paradigm by leveraging the physics of dose variation for treating large brain tumors. Further studies are underway to validate these effects in animal experiments.