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Session: Pre-Clinical Modeling [Return to Session]

A Cell Survival Model That Accounts for Sublethal Radiation Damage

O Vassiliev*, R Mohan, UT MD Anderson Cancer Center, Houston, TX


TU-D1030-IePD-F4-2 (Tuesday, 7/12/2022) 10:30 AM - 11:00 AM [Eastern Time (GMT-4)]

Exhibit Hall | Forum 4

Purpose: The amount of sublethal radiation damage (SRD) increases with increasing dose. This results in increasing radiosensitivity of surviving cells. This radiosensitization is expressed in survival curves as their slope increasing with increasing dose until it reaches its maximum value. We developed a cell survival model that accounts for accumulation of SRD and applied it to a set of measured cell survival data for protons with LETs from 1.1 to 19 keV/μm.

Methods: The model is based on a rigorous microdosimetry-based formalism. We make only one assumption - Poisson statistics for a number of protons entering a volume. All the key results are derived by exact algebra. The model has a maximum of four parameters, their number decreases with increasing LET, down to one. We investigated parameters using data from over 300 survival curves for x-rays, protons, helium and heavy ions. To apply the model to a set of proton survival data we performed a global fit of all survival curves simultaneously using optimization software.

Results: The model explains the linear-quadratic-linear form of survival curves. It predicts smooth transition from linear-quadratic to linear dependence with increasing dose and/or increasing LET. The model agrees with proton experimental data in terms of dose and LET dependencies. Accumulation of SRD begins at doses below 1 Gy and includes increasing the number of damaged cells and damage buildup in individual cells. At 10 Gy few cells remain unaffected by SRD. SRD impacts cell at random, which makes cell population heterogeneous in terms of radiosensitivity.

Conclusion: Accumulation of SRD is an important factor in cell response to radiation. Starting at doses below 1 Gy this process makes the population of surviving cells more radiosensitive and heterogeneous in terms of radiosensitivity. We have developed and tested a model that accounts for these effects.


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