A radiobiological model of reoxygenation and fractionation effects

Guerrero, Mariana; Carlson, David J.

doi:10.1002/mp.12194

Cited by 9 publications

(13 citation statements)

References 14 publications

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“…Recently, Guerrero and Carlson ( 20 ) developed a radiobiological model that quantifies the reoxygenation effect for different fractionations and modeled the hypoxic fraction in tumors as a function of the number of radiation treatments in order to develop a simple analytical expression for a reoxygenation term in biological effect calculations.…”

Section: Resultsmentioning

confidence: 99%

Radiobiological Optimization in Lung Stereotactic Body Radiation Therapy: Are We Ready to Apply Radiobiological Models?

et al. 2018

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Lung tumors are often associated with a poor prognosis although different schedules and treatment modalities have been extensively tested in the clinical practice. The complexity of this disease and the use of combined therapeutic approaches have been investigated and the use of high dose-rates is emerging as effective strategy. Technological improvements of clinical linear accelerators allow combining high dose-rate and a more conformal dose delivery with accurate imaging modalities pre- and during therapy. This paper aims at reporting the state of the art and future direction in the use of radiobiological models and radiobiological-based optimizations in the clinical practice for the treatment of lung cancer. To address this issue, a search was carried out on PubMed database to identify potential papers reporting tumor control probability and normal tissue complication probability for lung tumors. Full articles were retrieved when the abstract was considered relevant, and only papers published in English language were considered. The bibliographies of retrieved papers were also searched and relevant articles included. At the state of the art, dose–response relationships have been reported in literature for local tumor control and survival in stage III non-small cell lung cancer. Due to the lack of published radiobiological models for SBRT, several authors used dose constraints and models derived for conventional fractionation schemes. Recently, several radiobiological models and parameters for SBRT have been published and could be used in prospective trials although external validations are recommended to improve the robustness of model predictive capability. Moreover, radiobiological-based functions have been used within treatment planning systems for plan optimization but the advantages of using this strategy in the clinical practice are still under discussion. Future research should be directed toward combined regimens, in order to potentially improve both local tumor control and survival. Indeed, accurate knowledge of the relevant parameters describing tumor biology and normal tissue response is mandatory to correctly address this issue. In this context, the role of medical physicists and the AAPM in the development of radiobiological models is crucial for the progress of developing specific tool for radiobiological-based optimization treatment planning.

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Section: Resultsmentioning

confidence: 99%

Radiobiological Optimization in Lung Stereotactic Body Radiation Therapy: Are We Ready to Apply Radiobiological Models?

et al. 2018

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“…In the case when the target is comprised of only two‐compartments with different values of alpha and beta, it is more convenient to use a different quantity, referred to as radiobiological effect (

E_{tar}

), instead of

B E D_{italictar}

(e.g., Refs. [26,27]):

E_{italictar} = - \ln \overset{true¯}{S_{tar}} .

…”

Section: Methodsmentioning

confidence: 99%

Effect of reoxygenation on hypofractionated radiotherapy of prostate cancer

Kuperman

Lubich

2020

Medical Physics

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Purpose: To assess the role of reoxygenation of hypoxic tumor cells in hypofractionated radiotherapy of prostate cancer. Methods: The considered radiobiological model is based on the assumption of two populations (compartments) of cells: oxygenated (aerobic) cells and hypoxic cells. After each fraction of radiation, some of the hypoxic cells reoxygenate while a fraction of initially aerobic cells becomes hypoxic. The kinetics of this process between successive treatments is described by coupled, first-order differential equations. To determine the effect of reoxygenation on cell kill in the treatment target, we utilize the linear-quadratic (LQ) model assuming different radiosensitivities for the aerobic and hypoxic cells. Results: Analytical solutions for the number of surviving malignant cells are obtained for special cases of slow and fast reoxygenation. The radiobiological effect of reoxygenation for different fractionation regimens is also evaluated numerically. Conclusions: In this study, a radiobiological model for kinetics of reoxygenation in tumors is used to evaluate different fractionation schedules in radiotherapy of prostate cancer. The obtained results indicate that in the case of low alpha/beta ratio for malignant cells (e.g., α=β = 1.5 Gy), treatment schedule with 4-10 fractions and dose per fraction >4-5 Gy can result in increased cell kill in the treatment target at the same level of rectal toxicity as compared to conventional fractionation. The findings of this study also suggest that radiotherapy of the prostate with 1-3 fractions can be radiobiologically inferior to treatments with greater number of fractions.

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“…TOPAS has been successfully applied to research in radiation therapy physics and macroscopic organ or cellular biology. However, more fundamental research is needed to understand the underlying mechanisms of radiation action, describe effects of oxygenation, intracellular signaling, drug-induced radiation sensitization or resistance and many other effects (8)(9)(10). Variations at the (sub-)cellular (cellular and sub-cellular) level, both for tumors and surrounding normal tissues, need to be considered.…”

Section: Motivation For Topas-nbiomentioning

confidence: 99%

TOPAS-nBio: An Extension to the TOPAS Simulation Toolkit for Cellular and Sub-cellular Radiobiology

et al. 2018

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The TOPAS Monte Carlo (MC) system is used in radiation therapy and medical imaging research, having played a significant role in making Monte Carlo simulations widely available for proton therapy related research. While TOPAS provides detailed simulations of patient scale properties, the fundamental unit of the biological response to radiation is a cell. Thus, our goal was to develop TOPAS-nBio, an extension of TOPAS dedicated to advance understanding of radiobiological effects at the (sub-)cellular, (i.e., the cellular and sub-cellular) scale. TOPAS-nBio was designed as a set of open source classes that extends TOPAS to model radiobiological experiments. TOPAS-nBio is based on and extends Geant4-DNA, which extends the Geant4 toolkit, the basis of TOPAS, to include very low-energy interactions of particles down to vibrational energies, explicitly simulates every particle interaction (i.e., without using condensed histories) and propagates radiolysis products. To further facilitate the use of TOPAS-nBio, a graphical user interface was developed. TOPAS-nBio offers full track-structure Monte Carlo simulations, integration of chemical reactions within the first millisecond, an extensive catalogue of specialized cell geometries as well as sub-cellular structures such as DNA and mitochondria, and interfaces to mechanistic models of DNA repair kinetics. We compared TOPAS-nBio simulations to measured and published data of energy deposition patterns and chemical reaction rates (G values). Our simulations agreed well within the experimental uncertainties. Additionally, we expanded the chemical reactions and species provided in Geant4-DNA and developed a new method based on independent reaction times (IRT), including a total of 72 reactions classified into 6 types between neutral and charged species. Chemical stage simulations using IRT were a factor of 145 faster than with step-by-step tracking. Finally, we applied the geometric/chemical modeling to obtain initial yields of double-strand breaks (DSBs) in DNA fibers for proton irradiations of 3 and 50 MeV and compared the effect of including chemical reactions on the number and complexity of DSB induction. Over half of the DSBs were found to include chemical reactions with approximately 5% of DSBs caused only by chemical reactions. In conclusion, the TOPAS-nBio extension to the TOPAS MC application offers access to accurate and detailed multiscale simulations, from a macroscopic description of the radiation field to microscopic description of biological outcome for selected cells. TOPAS-nBio offers detailed physics and chemistry simulations of radiobiological experiments on cells simulating the initially induced damage and links to models of DNA repair kinetics.

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A radiobiological model of reoxygenation and fractionation effects

Cited by 9 publications

References 14 publications

Radiobiological Optimization in Lung Stereotactic Body Radiation Therapy: Are We Ready to Apply Radiobiological Models?

Radiobiological Optimization in Lung Stereotactic Body Radiation Therapy: Are We Ready to Apply Radiobiological Models?

Effect of reoxygenation on hypofractionated radiotherapy of prostate cancer

TOPAS-nBio: An Extension to the TOPAS Simulation Toolkit for Cellular and Sub-cellular Radiobiology

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