State-Driven Mathematical Model Simulations of Tumor Response to Radiotherapy: How Does High FDG Uptake Relate to Classical Radiobiological Principles?
J Jeong1*, J O Deasy2, (1) University of Missouri, Columbia, MO, (2) Memorial Sloan Kettering Cancer Center, New York, NYTH-C-213AB-9 Thursday 10:30:00 AM - 12:30:00 PM Room: 213AB
Purpose: High FDG-PET tracer tumor uptake is well-established to correlated to increased local failures and shorter overall survival. However, the relationship between uptake and classical radiobiological mechanisms is unclear. We explore the potential relationship between FDG-PET uptake and classical radiobiolocial mechanisms using a mathematical framework.
Methods: Tumor response was simulated using a novel, state-driven tumor response model, including proliferating, hypoxic, and intermediate cell sub-populations. Different potential relationships between FDG uptake and these cell populations were simulated. The uptake of FDG was assumed to be associated either with (1) the total number of viable cells, (2) the number of proliferative cells or (3) the number of intermediate cells. The predicted tumor doses for 50% control (TD50) in 2 Gy/fx were estimated for all possible initial conditions and correlated with the FDG uptake level for each assumption.
Results: When the FDG uptake pattern was assumed to reflect the level of proliferation, the TD50 decreased with high FDG uptake. When the FDG was assumed to reflect the fraction of viable cells, only a weak positive correlation was observed between FDG uptake and TD50. As a surrogate of metabolically-viable hypoxic cells, FDG uptake exhibited a strong positive correlation with TD50, consistent with clinical observations.
Conclusions: Several different FDG uptake patterns were simulated using the model. Given the established clinical fact that FDG uptake correlates to a requirement of higher dose to achieve local control, the results support a potential avidity of FDG for cells in the intermediate stress state between being well-oxygenated (and proliferating) and very poorly oxygenated (extremely hypoxic).