Ponente
Descripción
To evaluate the impact of various radiation types on biological damage, the Relative Biological Effectiveness (RBE) is defined as the ratio of doses required to produce a given biological response (endpoint) between the radiation source under study and a reference radiation type, typically photons. To potentially account for this in clinical practice, phenomenological and mechanistic models have been proposed to determine the RBE in particle therapy, such as the Microdosimetric Kinetic Model (MKM). The MKM introduces the concept of "domain" linked to the maximum distance over which sublethal lesions can interact, leading to lethal lesions and cell death. The size of the cell nucleus is also relevant to characterize how many lethal and sublethal lesions can be induced by radiation and at what point a lethal lesion is warranted from a given radiation.
Clonogenic experiments are important for this purpose because they determine the percentage of cells that keep their mitotic viability after exposure to ionizing radiation. The Particle Irradiation Database Ensemble (PIDE), developed at the GSI Helmholtz Center (Germany), is a database that provides data on irradiation conditions, the ion used, cell line information, and the parameters of the linear-quadratic model (LQ) for different clonogenic experiments. By analyzing these data derived from experimental campaigns with protons, alpha particles, or carbon ions, two key quantities of the MKM can be obtained: the statistical distribution of domain radius values and the cell nucleus radius. These parameters are used by the MKM to obtain the linear parameter (α) of the LQ model for a given radiation type.
In this work, survival curves obtained from clonogenic assays were employed to determine the values of cell-specific parameters mentioned above in a systematic way. This determination represents an approach to include further information on the cell line-specific radiosensitivity. Our results showed large variability among different cell lines [1], illustrating the importance of intrinsic response to radiation of different biological systems when determining RBE. The considerable deviations among groups and experiments raise the question of how valuable RBE models based on clonogenic assays are for the clinics. Also, the significant number of nuances to be considered in these models and the lack of connection with realistic biological processes in the clinical response to radiation contribute to challenging the translatability of clonogenic survival data in the clinic.
It is likely that a significant portion of the reported variability in PIDE comes from the fact that multiple institutions and laboratories carried out these experiments in different experimental conditions. Hence, standardized methods to perform clonogenic assays for different particles and energies, especially clinical ones, may help to decrease the variability observed in experimental results, leading to a better RBE assessment for clinical practice.
[1] D. Suárez-García et al. Radiother. Oncol. 185: 109730 (2023).
