Modeling Stereotactic Body Radiation Therapy (SBRT) Including Cell Cycle-Dependent Radiosensitivity, Hypoxia, Reoxygenation and Proliferation: Is SBRT Explainable Based On Classical Radiobiological Factors?
J Jeong1*, J O Deasy2, (1) University of Missouri, Columbia, MO, (2) Memorial Sloan Kettering Cancer Center, New York, NYSU-C-BRB-6 Sunday 1:30:00 PM - 2:15:00 PM Room: Ballroom B
Purpose: The tumoricidal effectiveness of standard fractionation radiotherapy is usually understood qualitatively in terms of proliferation, hypoxia, and reoxygenation. We have developed a novel, state-based computational model that includes those factors. The efficacy of SBRT has been hypothesized to be due to other factors, such as apoptosis of vasculature and/or immune-response factors. The goal of this project is to see if SBRT can potentially be explained using only those classical radiobiology factors.
Methods: The state-based computational model considers the cell cycle effect on radiosensitivity and cycle reassortment. Varying fractionation schemes were compared in terms of model predicted equivalent dose at 2 Gy/fx (EQD_model). Using relevant parameters for lung cancer tumors, the EQD_model was estimated for several typical SBRT regimes.
Results: SBRT is predicted to benefit from less repopulation (as expected) and high cell-kill relative effectiveness, but is also predicted to suffer from less reoxygenation and the absence of cell-cycle reassortment. Overall, the model predicted EQD_model was significantly reduced from the BED-based NTD2 (NTD2=BED/1.2, assuming alpha/beta=10), typically by about 25-30%. The treatment duration of SBRT affected the treatment efficacy and the ratio of EQD_model/NTD2 was lowest for high dose single fraction SBRT (~60%). With longer treatment duration, the EQD_model increased and approached to NTD2, due to increased reoxygenation. For most evaluated SBRT regimens, predicted cell-survival levels were too high to account for the reported high local-response rates of the SBRT outcomes.
Conclusions: Considering four Rs of radiobiology, the equivalent dose in 2 Gy/fx was estimated for several SBRT regimes. The treatment efficacy of SBRT estimated from BED is significantly overestimated compared to the model results and the SBRT schedule seems to affect the treatment efficacy. Non-classical biological or radiobiological principals are apparently at work in high-dose SBRT treatments.