arXiv subjects

Isabel González-Crespo

Publications and source records attributed to Isabel González-Crespo.

4 recordsLinked to original sources

arXiv2026

On the calculation of the radiobiological effect of radiolytic oxygen depletion in FLASH radiotherapy

Objective: Radiolytic oxygen depletion (ROD) may play a role in the sparing of cells irradiated with ultra-high dose rates. Different methods have been used to quantify the effect of ROD during FLASH irradiation on cell survival, typically involving some kind of averaging of the oxygen effect and the LQ model. In this work, we compare the results obtained with several of these methods and introduce a novel method based on the non-linear differential form of the LQ model. Approach: We present a novel method to account for a varying oxygen concentration on the dose-response based on the non-linear differential form of the LQ model, and we compare the results obtained with this method with those obtained with other methods that linearize the averaging of the oxygen effect during irradiation. Main results: We found differences in the surviving fractions obtained with the method introduced in this work and other methods that introduce different linearizations (averaging) of the non-linear dependence on the oxygen concentration, especially for oxygenations and doses that lead to important changes in the OERs during the delivery of the dose (initial oxygenations $\approx$5--10 mmHg and doses $>30$~Gy). On the other hand, we showed that the method presented by Zhu \emph{et al.} is equivalent to a first-order Euler numerical method of the differential LQ model. Significance: The method introduced in this work and the method of Zhu \emph{et al.} may allow a more precise quantification of the effect of ROD on dose-response, both for tumors and normal tissues. While all the reviewed methods show an oxygen-dependent sparing effect of FLASH radiotherapy driven by ROD and qualitatively similar results, the method introduced in this work and that of Zhu \emph{et al.} may be more suitable to quantitatively analyze new preclinical (and future clinical) data coming from experimental studies.

physics.med-ph↗

arXiv2023

Variation of the relative biological effectiveness with fractionation in proton therapy: analysis of prostate cancer response

Purpose: To present a methodology to analyze the variation of RBE with fractionation from clinical data of tumor control probability (TCP) and to apply it to study the response of prostate cancer to proton therapy. M&M: We analyzed the dependence of the RBE on the dose per fraction by using the LQ model and the Poisson TCP formalism. Clinical TCPs for prostate cancer treated with photon and proton therapy for conventional fractionation (2 Gy(RBE)x37 fractions), moderate hypofractionation (3 Gy(RBE)x20 fractions) and hypofractionation (7.25 Gy(RBE)x5 fractions) were obtained from the literature and analyzed. Results: The theoretical analysis showed three distinct regions with RBE monotonically decreasing, increasing or staying constant with the dose per fraction, depending on the change of (α, \{beta}) values between photon and proton irradiation (the equilibrium point being at(α_p/\{beta}_p)=(α_X/\{beta}_X)(α_X/α_p)). An analysis of the clinical data showed RBE values that decline with increasing dose per fraction: for low risk RBE=1.124, 1.119, and 1.102 for 1.82 Gy, 2.73 Gy and 6.59 Gy per fraction (physical proton doses), respectively; for intermediate risk RBE=1.119, and 1.102 for 1.82 Gy, and 6.59 Gy per fraction (physical proton doses), respectively. These values are nonetheless very close to the nominal 1.1 value. Conclusions: We presented a methodology to analyze the RBE for different fractionations, and we used it to study clinical data for prostate cancer. The analysis shows a monotonically decreasing RBE with increasing dose per fraction, which is expected from the LQ formalism and the changes in (α, \{beta}) between photon and proton irradiation. However, the calculations in this study have to be considered with care as they may be biased by limitations in the modeling and/or by the clinical data set used for the analysis.

physics.med-ph↗

arXiv2023

An in-silico study of conventional and FLASH radiotherapy iso-effectiveness: Radiolytic oxygen depletion and its potential impact on tumor control probability

FLASH radiotherapy (FLASH-RT) has shown the potential to spare normal tissue while seemingly maintaining the effectiveness of conventional radiotherapy (CONV-RT). It has been suggested that the protective effect arises from the radiolytic oxygen depletion (ROD) caused by FLASH-RT, but it is not entirely clear why this protective effect is not observed in tumors. Iso-effectiveness has been experimentally observed in time-volume curves of preclinical tumors irradiated with FLASH and conventional radiotherapy, but it may not translate to clinical trials, where tumor control probability (TCP) is typically the investigated endpoint. In this work, we used mathematical models to investigate the iso-effectiveness of FLASH-RT/CONV-RT on tumors, focusing on the role of ROD. We used a spatiotemporal reaction-diffusion model, including ROD, to simulate tumor oxygenation. From those oxygen distributions we obtained surviving fractions (SFs), using the linear-quadratic model with oxygen enhancement ratios (OER). We then used the calculated SFs to describe the evolution of preclinical tumor volumes through a mathematical model of tumor response. We also calculated TCPs using the Poisson-LQ approach. Our study suggests that ROD causes differences in SF between FLASH-RT and CONV-RT, especially in low $α$/$β$ and poorly oxygenated cells. These changes do not lead to significant differences in the evolution of preclinical tumors. However, when extrapolating this effect to TCP curves, we observed important differences between both techniques (TCP is lower in FLASH-RT). Nonetheless, it cannot be discarded that other effects not modeled in this work could contribute to tumor control and maintain the iso-effectiveness of FLASH-RT.

physics.med-ph↗

arXiv2022

A biomathematical model of tumor response to radioimmunotherapy with $α$PDL1 and $α$CTLA4

There is evidence of synergy between radiotherapy and immunotherapy. Radiotherapy can increase liberation of tumor antigens, causing activation of antitumor T-cells. This effect can be boosted with immunotherapy. Radioimmunotherapy has potential to increase tumor control rates. Biomathematical models of response to radioimmunotherapy may help on understanding of the mechanisms affecting response, and assist clinicians on the design of optimal treatment strategies. In this work we present a biomathematical model of tumor response to radioimmunotherapy. The model uses the linear-quadratic response of tumor cells to radiation (or variation of it), and builds on previous developments to include the radiation-induced immune effect. We have focused this study on the combined effect of radiotherapy and $α$PDL1/$α$CTLA4 therapies. The model can fit preclinical data of volume dynamics and control obtained with different dose fractionations and $α$PDL1/$α$CTLA4. A biomathematical study of optimal combination strategies suggests that a good understanding of the involved biological delays, the biokinetics of the immunotherapy drug, and the interplay between them, may be of paramount importance to design optimal radioimmunotherapy schedules. Biomathematical models like the one we present can help to interpret experimental data on the synergy between radiotherapy and immunotherapy, and to assist in the design of more effective treatments.

physics.med-ph↗