Author: Alejandro Bertolet, Jose Antonio Lopez-Valverde, Victor V. Onecha, Daniel Puerta 👨🔬
Affiliation: Dana Farber Cancer Institute/Brigham and Women's Hospital, Departamento de Física Atómica, Molecular y Nuclear, Universidad de Granada, Massachusetts General Hospital and Harvard Medical School 🌍
Purpose: Besides its superior dose conformity, proton therapy induces greater damage to tissue than conventional radiotherapies. This increased damage is usually quantified through the concept of relative biological effectiveness (RBE). As there are decades of experience studying prescription doses and their effects in conventional radiotherapy, we need models that can accurately determine RBE to harness accumulated clinical experience.
In this work, we use ChronoRepair, an agent-based model for the repair of radiation-induced cellular damage, to investigate the evolution of cell viabilities after photon and proton irradiation and, thus, estimate RBE.
Methods: ChronoRepair simulates the evolution of the DNA damage in a cell during and after irradiation considering specific repair mechanisms of DNA damage. The algorithm requires initial distributions of DNA damage as input, which were computed using TOPAS-nBio, a track-structure Monte Carlo toolkit.
ChronoRepair includes an exhaustive variety of parameters in the simulation, such as cell cycle phase, DNA structure, and preferred repair mechanism. Here, we analyzed a generic cell model with ChronoRepair current defaults for the cellular parameters and tested ChronoRepair’s sensitivity by considering its three repair options.
Survival curves and foci evolution were simulated for a generic cell 24 h post irradiation for 250 keV photons and 0.5 MeV protons for the different repair options.
Results: Our findings include: 1) proton survival curves are more sensitive to repair option choice; 2) foci evolution is similar for photons and protons; and 3) the model successfully reproduces an RBE of 1.1–1.6, depending on the survival endpoint.
Conclusion: Our preliminary but key results for the irradiation of a generic cell with different radiation qualities and repair models showcase the promise of ChronoRepair to characterize complex relative biological differences between radiation modalities. We aim to expand this work by using ChronoRepair to model cell lines based on experimental data.