Ponente
Descripción
The efficacy of radiation therapy in oncological treatment depends on multiple interrelated physical, chemical, and biological effects. Agent-based computational models have emerged as invaluable tools for elucidating these intricate interactions, although existing models predominantly rely on absorbed dose as the sole metric for predicting tumor response. Mechanistic models that incorporate tumor microenvironmental factors into the biological response to radiation are therefore necessary.
To address this gap, we introduce AMBER (Agent-based Modeling of Biophysical Evolution after Radiotherapy), a novel hybrid computational framework that synergistically combines agent-based and continuum approaches within a voxelized geometry. AMBER is engineered to simulate four fundamental mechanisms governing tumor dynamics: (i) cellular proliferation and migration, (ii) microenvironmental oxygenation, (iii) angiogenic signaling, and (iv) cellular fate determination. Specifically, AMBER employs Gamma-distributed cellular division times within each voxel and diffusive migration to adjacent voxels. Oxygen distribution is calibrated through sub-voxel simulations based on vessel density and cellular crowding, represented by a Beta distribution. Angiogenesis is modeled as a directed random walk influenced by vascular endothelial growth factor (VEGF) gradients and cellular crowding. Cellular vitality, a composite metric, is evaluated at each time step to categorize cells as either cycling, quiescent, or undergoing apoptosis/necrosis.
Radiation effects are incorporated using dose metrics obtained from the TOPAS Monte Carlo toolkit, with cell death modeled as a dose-dependent phenomenon following a log-normal time distribution. AMBER is thus uniquely positioned to simulate the impact of fractionated radiation doses on tumor dynamics, taking into account both microenvironmental and radiosensitivity variables. Preliminary results, depicted in Figure 1, demonstrate the capability of the model to simulate the effects of 6 MeV gamma irradiation over a five-day course on both cellular count and tumor volume.
AMBER is designed as a modular piece of code thought to be extended, facilitating the future integration of high-fidelity radiation bioeffect models such as TOPAS-nBio, as well as models elucidating DNA damage and repair mechanisms. This makes AMBER a versatile and comprehensive tool for advancing our understanding of the complex interplay between radiation therapy and tumor biology.
