Nouvelles approches en Radiothérapie

Publications de l’équipe

Année de publication : 2017

Immaculada Martínez-Rovira, Josep Puxeu-Vaqué, Yolanda Prezado (2017 Jul 25)

Dose evaluation of Grid Therapy using a 6 MV flattening filter-free (FFF) photon beam: A Monte Carlo study.

Medical physics : 5378-5383 : DOI : 10.1002/mp.12485 En savoir plus
Résumé

Spatially fractionated radiotherapy is a strategy to overcome the main limitation of radiotherapy, i.e., the restrained normal tissue tolerances. A well-known example is Grid Therapy, which is currently performed at some hospitals using megavoltage photon beams delivered by Linacs. Grid Therapy has been successfully used in the management of bulky abdominal tumors with low toxicity. The aim of this work was to evaluate whether an improvement in therapeutic index in Grid Therapy can be obtained by implementing it in a flattening filter-free (FFF) Linac. The rationale behind is that the removal of the flattening filter shifts the beam energy spectrum towards lower energies and increase the photon fluence. Lower energies result in a reduction of lateral scattering and thus, to higher peak-to-valley dose ratios (PVDR) in normal tissues. In addition, the gain in fluence might allow using smaller beams leading a more efficient exploitation of dose-volume effects, and consequently, a better normal tissue sparing.

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Jayde Livingstone, Jean François Adam, Jeffrey C Crosbie, Chris J Hall, Jessica E Lye, Jonathan McKinlay, Daniele Pelliccia, Frédéric Pouzoulet, Yolanda Prezado, Andrew W Stevenson, Daniel Häusermann (2017 Jul 1)

Preclinical radiotherapy at the Australian Synchrotron’s Imaging and Medical Beamline: instrumentation, dosimetry and a small-animal feasibility study.

Journal of synchrotron radiation : 854-865 : DOI : 10.1107/S1600577517006233 En savoir plus
Résumé

Therapeutic applications of synchrotron X-rays such as microbeam (MRT) and minibeam (MBRT) radiation therapy promise significant advantages over conventional clinical techniques for some diseases if successfully transferred to clinical practice. Preclinical studies show clear evidence that a number of normal tissues in animal models display a tolerance to much higher doses from MRT compared with conventional radiotherapy. However, a wide spread in the parameters studied makes it difficult to make any conclusions about the associated tumour control or normal tissue complication probabilities. To facilitate more systematic and reproducible preclinical synchrotron radiotherapy studies, a dedicated preclinical station including small-animal irradiation stage was designed and installed at the Imaging and Medical Beamline (IMBL) at the Australian Synchrotron. The stage was characterized in terms of the accuracy and reliability of the vertical scanning speed, as this is the key variable in dose delivery. The measured speed was found to be within 1% of the nominal speed for the range of speeds measured by an interferometer. Furthermore, dose measurements confirm the expected relationship between speed and dose and show that the measured dose is independent of the scan direction. Important dosimetric parameters such as peak dose, valley dose, the collimator output factor and peak-to-valley dose ratio are presented for 5 mm × 5 mm, 10 mm × 10 mm and 20 mm × 20 mm field sizes. Finally, a feasibility study on three glioma-bearing rats was performed. MRT and MBRT doses were prescribed to achieve an average dose of 65 Gy in the target, and magnetic resonance imaging follow-up was performed at various time points after irradiation to follow the tumour volume. Although it is impossible to draw conclusions on the different treatments with such a small number of animals, the feasibility of end-to-end preclinical synchrotron radiotherapy studies using the IMBL preclinical stage is demonstrated.

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Immaculada Martínez-Rovira, Wilfredo González, Stephan Brons, Yolanda Prezado (2017 May 31)

Carbon and oxygen minibeam radiation therapy: An experimental dosimetric evaluation.

Medical physics : 4223-4229 : DOI : 10.1002/mp.12383 En savoir plus
Résumé

To perform dosimetric characterization of a minibeam collimator in both carbon and oxygen ion beams to guide optimal setup geometry and irradiation for future radiobiological studies.

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Wilfredo González, Cécile Peucelle, Yolanda Prezado (2017 Feb 26)

Theoretical dosimetric evaluation of carbon and oxygen minibeam radiation therapy.

Medical physics : 1921-1929 : DOI : 10.1002/mp.12175 En savoir plus
Résumé

Charged particles have several advantages over x-ray radiations, both in terms of physics and radiobiology. The combination of these advantages with those of minibeam radiation therapy (MBRT) could help enhancing the therapeutic index for some cancers with poor prognosis. Among the different ions explored for therapy, carbon ions are considered to provide the optimum physical and biological characteristics. Oxygen could be advantageous due to a reduced oxygen enhancement ratio along with a still moderate biological entrance dose. The aforementioned reasons justified an in-depth evaluation of the dosimetric features of carbon and oxygen minibeam radiation therapy to establish the interest of further explorations of this avenue.

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Asuncion Carmona, Stéphane Roudeau, Baptiste L'Homel, Frédéric Pouzoulet, Sarah Bonnet-Boissinot, Yolanda Prezado, Richard Ortega (2017 Feb 23)

Heterogeneous intratumoral distribution of gadolinium nanoparticles within U87 human glioblastoma xenografts unveiled by micro-PIXE imaging.

Analytical biochemistry : 50-57 : DOI : S0003-2697(17)30080-5 En savoir plus
Résumé

Metallic nanoparticles have great potential in cancer radiotherapy as theranostic drugs since, they serve simultaneously as contrast agents for medical imaging and as radio-therapy sensitizers. As with other anticancer drugs, intratumoral diffusion is one of the main limiting factors for therapeutic efficiency. To date, a few reports have investigated the intratumoral distribution of metallic nanoparticles. The aim of this study was to determine the quantitative distribution of gadolinium (Gd) nanoparticles after direct intratumoral injection within U87 human glioblastoma tumors grafted in mice, using micro-PIXE (Particle Induced X-ray Emission) imaging. AGuIX (Activation and Guiding of Irradiation by X-ray) 3 nm particles composed of a polysiloxane network surrounded by gadolinium chelates were used. PIXE results indicate that the direct injection of Gd nanoparticles in tumors results in their heterogeneous diffusion, probably related to variations in tumor density. All tumor regions contain Gd, but with markedly different concentrations, with a more than 250-fold difference. Also Gd can diffuse to the healthy adjacent tissue. This study highlights the usefulness of mapping the distribution of metallic nanoparticles at the intratumoral level, and proposes PIXE as an imaging modality to probe the quantitative distribution of metallic nanoparticles in tumors from experimental animal models with micrometer resolution.

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Consuelo Guardiola, Cécile Peucelle, Yolanda Prezado (2017 Jan 28)

Optimization of the mechanical collimation for minibeam generation in proton minibeam radiation therapy.

Medical physics : 1470-1478 : DOI : 10.1002/mp.12131 En savoir plus
Résumé

The dose tolerances of normal tissues continue to be the main barrier in radiation therapy. To lower it, a novel concept based on a combination of proton therapy and the use of arrays of parallel and thin beams has been recently proposed: proton minibeam radiation therapy (pMBRT). It allies the inherent advantages of protons with the remarkable normal tissue preservation observed when irradiated with submillimetric spatially fractionated beams. Due to multiple Coulomb scattering, the tumor receives a homogeneous dose distribution, while normal tissues in the beam path benefit from the spatial fractionation of the dose. This promising technique has already been implemented at a clinical center (Proton therapy Center of Orsay) by means of a first prototype of a multislit collimator. The main goal of this work was to optimize the minibeam generation by means of a mechanical collimation.

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Année de publication : 2016

Audrey Bouchet, Elke Bräuer-Krisch, Yolanda Prezado, Michèle El Atifi, Léonid Rogalev, Céline Le Clec'h, Jean Albert Laissue, Laurent Pelletier, Géraldine Le Duc (2016 Jun 22)

Better Efficacy of Synchrotron Spatially Microfractionated Radiation Therapy Than Uniform Radiation Therapy on Glioma.

International journal of radiation oncology, biology, physics : 1485-1494 : DOI : S0360-3016(16)30030-X En savoir plus
Résumé

Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly focused synchrotron beam into arrays of parallel microbeams, typically a few tens of microns wide and depositing several hundred grays. This irradiation modality was shown to have a high therapeutic impact on tumors, especially in intracranial locations. However, mechanisms responsible for such a property are not fully understood.

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Ibraheem Yousef, Olivier Seksek, Sílvia Gil, Yolanda Prezado, Josep Sulé-Suso, Immaculada Martínez-Rovira (2016 Mar 3)

Study of the biochemical effects induced by X-ray irradiations in combination with gadolinium nanoparticles in F98 glioma cells: first FTIR studies at the Emira laboratory of the SESAME synchrotron.

The Analyst : 2238-49 : DOI : 10.1039/c5an02378e En savoir plus
Résumé

One strategy to improve the clinical outcome of radiotherapy is to use nanoparticles as radiosensitizers. Along this line, numerous studies have shown the enhanced effectiveness of tumour cell killing when nanoparticles are exposed to irradiation. However, the mechanisms of action are not clear yet. In addition to the damage due to a possible local radiation dose enhancement, the interaction of nanoparticles with essential biological macromolecules could lead to changes in the cells, such as cell arrest at radiosensitive phases. Within this framework, vibrational spectroscopy was used to investigate the biochemical changes in F98 glioma cells induced by X-ray irradiations combined with gadolinium nanoparticles. Fourier transform infrared (FTIR) microspectroscopy experiments were performed at the Emira laboratory of the SESAME synchrotron (Jordan), allowing the characterisation of spectral signatures of nanoparticle-induced effects in glioma cells. Multivariate analysis of the spectra recorded using principal component analysis reveals clear differences in the DNA, protein and lipid regions in the presence of nanoparticles. Prior to irradiation, results show that nanoparticles induce biochemical modifications in the cells, probably due to changes in the cellular function. Biochemical alterations are amplified in the presence of radiation. In particular, variations in the intensity and in the position of the PO2(-) symmetric and asymmetric modes are observed due to radiation damage to the DNA, which is increased in nanoparticle-treated cells. At 24 hours post-irradiation, biochemical changes related to the hallmark characteristics of cell death are detected. This includes a shift towards low wavenumbers in the amide I and II bands, relative amplitude changes in the CH2 and CH3 stretching modes, along with DNA chromatin condensation indications. Results were confirmed by two complementary cell viability assays.

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Année de publication : 2015

Yolanda Prezado, Pierre Deman, Pascale Varlet, Gregory Jouvion, Silvia Gil, Céline Le Clec'H, Hélène Bernard, Géraldine Le Duc, Sukhena Sarun (2015 Aug 19)

Tolerance to Dose Escalation in Minibeam Radiation Therapy Applied to Normal Rat Brain: Long-Term Clinical, Radiological and Histopathological Analysis.

Radiation research : 314-21 : DOI : 10.1667/RR14018.1 En savoir plus
Résumé

The major limitation to reaching a curative radiation dose in radioresistant tumors such as malignant gliomas is the high sensitivity to radiation and subsequent damage of the surrounding normal tissues. Novel dose delivery methods such as minibeam radiation therapy (MBRT) may help to overcome this limitation. MBRT utilizes a combination of spatial fractionation of the dose and submillimetric (600 μm) field sizes with an array (« comb ») of parallel thin beams (« teeth »). The dose profiles in MBRT consist of peaks and valleys. In contrast, the seamless irradiations of the several squared centimeter field sizes employed in standard radiotherapy result in homogeneous dose distributions (and consequently, flat dose profiles). The innovative dose delivery methods employed in MBRT, unlike standard radiation therapy, have demonstrated remarkable normal tissue sparing. In this pilot work, we investigated the tolerance of the rat brain after whole-brain MBRT irradiation. A dose escalation was used to study the tissue response as a function of dose, so that a threshold could be established: doses as high as 100 Gy in one fraction were still well tolerated by the rat brain. This finding suggests that MBRT may be used to deliver higher and potentially curative radiation doses in clinical practice.

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