Author: Ignacio Espinoza, Ignacio Narea, Beatriz Sanchez-Nieto π¨βπ¬
Affiliation: Institute of Physics, Pontificia Universidad CatΓ³lica de Chile π
Purpose: This study aims to evaluate the tumor response to combined radiochemotherapy on MCF7 spheroids using an open-source multiscale computational framework. The model provides a platform to simulate realistic tumor microenvironments, optimizing treatment strategies through the integration of experimental and theoretical insights.
Methods: PhysiCell, a physics-based simulator, was utilized to model 3D tumor spheroids. The model incorporated key features such as oxygen diffusion, drug transport, and cell cycle dynamics. Cisplatin was used for chemotherapy modeling, with IC50 values derived from literature and experimental data, while radiotherapy was implemented using a modified linear-quadratic model, including oxygen enhancement ratio (OER) and cell cycle effects. Simulations explored individual and combined therapy strategies, including neoadjuvant, adjuvant, and concomitant approaches.
Results: The model accurately reproduced key biological phenomena, including oxygen gradients, hypoxia-induced necrosis, and Gompertzian growth patterns. The calibrated doubling time of 45 hours and cell cycle phase distributions closely matched experimental observations. Chemotherapy simulations yielded an IC50 of 13.62 Β± 0.43 ΞΌM for cisplatin, consistent with literature values. Radiotherapy simulations demonstrated expected cell survival, with diminished efficacy observed in hypoxic conditions. Combined radiochemotherapy showed superior tumor volume reduction in neoadjuvant setups.
Conclusion: This computational framework successfully models the effects of radiochemotherapy on tumor spheroids, providing a validated platform for studying treatment efficacy. The findings highlight the importance of therapy timing and sequencing, offering a basis for future preclinical validations and optimization of therapeutic protocols.