Modeling cell response to low doses of photon irradiation—Part 1: on the origin of fluctuations

Cunha, Micaela; Testa, É.; Komova, O. V.; Nasonova, Elena; Mel'nikova, L. A.; Shmakova, N.L.; Beuve, M.

doi:10.1007/s00411-015-0621-6

Cited by 8 publications

(6 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this sense, starting from concepts of the existing models, such as the notion of local and sublethal events, we resorted to microdosimetry and nanodosimetry to implement a fully statistical methodology. Indeed, the magnitude of fluctuations in energy deposition at micrometric and nanometric scales is not negligible and cannot be disregarded (Cunha et al 2016b). With NanOx, it is also possible to obtain the α and β coefficients of the LQ model, which would allow for the implementation of the model in a TPS.…”

Section: Introductionmentioning

confidence: 99%

“…where C norm is a normalization factor ensuring that the average of cell survival over all irradiation configurations leads to the experimental probability of cell survival to an irradiation with a reference radiation characterized by the coefficients α r and β r of the respective LQ fit. C norm , α G and β G are determined as a function of the α r and β r coefficients through the convolution of the cell survival for a given configuration of radiation impacts c K with a Gaussian law knowing that: (1) for an irradiation with low-LET photons, the distribution of energy depositions at a microscopic scale corresponding to that of cell dimensions can be modeled by a Gaussian law (Cunha et al 2016b); and (2) the cell survival to a given configuration c K can be determined from the specific energy Z cK in the sensitive volume, i.e.…”

mentioning

confidence: 99%

See 1 more Smart Citation

NanOx, a new model to predict cell survival in the context of particle therapy

Cunha¹,

Monini²,

Testa³

et al. 2017

Phys. Med. Biol.

View full text Add to dashboard Cite

Particle therapy is increasingly attractive for the treatment of tumors and the number of facilities offering it is rising worldwide. Due to the well-known enhanced effectiveness of ions, it is of utmost importance to plan treatments with great care to ensure tumor killing and healthy tissues sparing. Hence, the accurate quantification of the relative biological effectiveness (RBE) of ions, used in the calculation of the biological dose, is critical. Nevertheless, the RBE is a complex function of many parameters and its determination requires modeling. The approaches currently used have allowed particle therapy to thrive, but still show some shortcomings. We present herein a short description of a new theoretical framework, NanOx, to calculate cell survival in the context of particle therapy. It gathers principles from existing approaches, while addressing some of their weaknesses. NanOx is a multiscale model that takes the stochastic nature of radiation at nanometric and micrometric scales fully into account, integrating also the chemical aspects of radiation-matter interaction. The latter are included in the model by means of a chemical specific energy, determined from the production of reactive chemical species induced by irradiation. Such a production represents the accumulation of oxidative stress and sublethal damage in the cell, potentially generating non-local lethal events in NanOx. The complementary local lethal events occur in a very localized region and can, alone, lead to cell death. Both these classes of events contribute to cell death. The comparison between experimental data and model predictions for the V79 cell line show a good agreement. In particular, the dependence of the typical shoulders of cell survival curves on linear energy transfer are well described, but also the effectiveness of different ions, including the overkill effect. These results required the adjustment of a number of parameters compatible with the application of the model in a clinical scenario thereby showing the potential of NanOx. Said parameters are discussed in detail in this paper.

show abstract

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

NanOx, a new model to predict cell survival in the context of particle therapy

Cunha¹,

Monini²,

Testa³

et al. 2017

Phys. Med. Biol.

View full text Add to dashboard Cite

show abstract

“…Thus, a new theoretical framework, called NanOx ® (41), was created gathering principles from existing approaches, while addressing some of their weaknesses (42,43). NanOx ® is a multiscale model that takes the stochastic nature of radiation at nanometric and micrometric scales fully into account, which has been shown to be drastically important (42)(43)(44). It also integrates the chemical aspects of radiation-matter interaction by means of a chemical specific energy, a new quantity determined from the production of reactive chemical species induced by irradiation (45).…”

Section: Biophysical Modelization Of Cell and Tissue Responses To Parmentioning

confidence: 99%

Translational research in radiobiology in the framework of France HADRON national collaboration

Rodriguez-Lafrasse¹,

Saintigny²,

Chevalier³

et al. 2017

Transl. Cancer Res

View full text Add to dashboard Cite

show abstract

“…This notion was reused to describe processes leading to cell death due to energy deposition at the nanometric scale. However, as it was shown that the magnitude of fluctuations of such energy deposition cannot be disregarded [18], the local dose was replaced in NanOx by a stochastic quantity representing the physico-chemical mechanisms. This is in contrast to the latest version of the LEM [11,19], where the biological effect of ions is primarily linked to the initial distribution of DNA doublestrand breaks (DSB) induced by radiation rather than the local dose itself.…”

Section: Introductionmentioning

confidence: 99%

Formalism of the NanOx biophysical model for radiotherapy applications

et al. 2023

Self Cite

View full text Add to dashboard Cite

Introduction: NanOx is a theoretical framework developed to predict cell survival to ionizing radiation in the context of radiotherapy. Based on statistical physics, NanOx takes the stochastic nature of radiation at different spatial scales fully into account. It extends concepts from microdosimetry to nanodosimetry, and considers as well the primary oxidative stress. This article presents in detail the general formalism behind NanOx.Methods: Cell death induction in NanOx is modeled through two types of biological events: the local lethal events, modeled by the inactivation of nanometric sensitive targets, and the global events, represented by the toxic accumulation of oxidative stress and sublethal lesions. The model is structured into general premises and postulates, the theoretical bases compliant with radiation physics and chemistry, and into simplifications and approximations, which are required for its practical implementation.Results: Calculations performed with NanOx showed that the energy deposited in the penumbra of ion tracks may be neglected for the low-energy ions encountered in some radiotherapy techniques, such as targeted radionuclide therapy. On the other hand, the hydroxyl radical concentration induced by ions was shown to be larger for low-LET ions and to decrease faster with time compared to photons. Starting from the general formalism of the NanOx model, an expression was derived for the cell survival to local lethal events in the track-segment approximation.Discussion: The NanOx model combines premises of existing biophysical models with fully innovative features to consider the stochastic effects of radiation at all levels in order to estimate cell survival and the relative biological effectiveness of ions. The details about the NanOx model formalism given in this paper allow anyone to implement the model and modify it by introducing different approximations and simplifications to improve it, or even adapt it to other medical applications.

show abstract

Modeling cell response to low doses of photon irradiation—Part 1: on the origin of fluctuations

Cited by 8 publications

References 32 publications

NanOx, a new model to predict cell survival in the context of particle therapy

NanOx, a new model to predict cell survival in the context of particle therapy

Translational research in radiobiology in the framework of France HADRON national collaboration

Formalism of the NanOx biophysical model for radiotherapy applications

Contact Info

Product

Resources

About