Tumor Control in RG2 Glioma-Bearing Rats: A Comparison Between Proton Minibeam Therapy and Standard Proton Therapy

Prezado, Yolanda; Jouvion, Grégory; Guardiola, Consuelo; González, Wilfredo; Juchaux, Marjorie; Bergs, Judith; Nauraye, C.; Labiod, Dalila; Marzi, Ludovic De; Pouzoulet, F.; Patriarca, Annalisa; Dendale, R.

doi:10.1016/j.ijrobp.2019.01.080

Cited by 60 publications

(87 citation statements)

References 7 publications

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“…One of the main advantages of pMBRT is the fact that dose homogenization can be obtained in the target with a single array, while normal tissues at the entrance profit from a PVDR high enough to ensure sparing effects . However, dose homogenization is not strictly needed in pMBRT for tumor control …”

Section: Resultsmentioning

confidence: 99%

“…Nevertheless, helium ions might still present a valuable and viable option for MBRT as several experiments indicate that a completely homogeneous dose coverage may not to be strictly needed to achieve tumor control. Instead, it was found in in vitro and animal experiments that, as long as a certain valley dose is assured in the target, a heterogenous target dose can still provide tumor sterilization . Experimental biological evaluations will be needed to assess whether this also holds for the case for HeMBRT.…”

Section: Resultsmentioning

confidence: 99%

“…For a perfect homogenization, an optimization algorithm would have been needed. However, our recent results from proton minibeam irradiation of small rodents indicate that tumor control can be achieved even with heterogeneous dose distributions …”

Section: Methodsmentioning

confidence: 99%

“…1,11 However, dose homogenization is not strictly needed in pMBRT for tumor control. 13,14 Provided the same c-t-c distance, helium ions also yield a higher PVDR than protons which would be beneficial for tissue sparing. At a c-t-c distance of 3.5 mm and an intermediate depth of 4 cm, helium minibeams still reach a PVDR of about 40 while the PVDR for protons is already below 10 ( Fig.…”

Section: B Dose Distributionsmentioning

confidence: 99%

“…The expected gain in normal tissue dose tolerances might allow a safe dose escalation in the tumor from which a higher tumor control may be expected. Along this line, proton minibeam radiation therapy has already shown a remarkable reduction of neurotoxicity as well as an important tumor control effectiveness in high‐grade gliomas in small animal experiments …”

Section: Introductionmentioning

confidence: 99%

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Improving the dose distributions in minibeam radiation therapy: Helium ions vs protons

2019

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Purpose Charged particle minibeam radiation therapy is a novel therapeutic strategy aiming at reducing the normal tissue complication probability by combining the normal tissue sparing of submillimetric, spatially fractionated beams with the improved dose deposition of ions. This may allow a safe dose escalation in the tumor and other targets. In particular, proton minibeam radiation therapy has already proven a remarkable increase of the therapeutic index for high‐grade gliomas in animal experiments. The reduced multiple Coulomb scattering and nuclear fragmentation of helium ions compared to protons and heavier ions, respectively, make them a good candidate for minibeam radiation therapy (MBRT). The purpose of the present work was to perform a comprehensive dosimetric comparison between proton and helium MBRT (pMBRT and HeMBRT). Methods Proton and helium minibeams of the same range (7.7 cm) have been simulated in a water phantom and in CT images of an anonymized human head. The Monte Carlo simulation toolkit GATE v8.0 was used. Different beam sizes (1 and 3 mm) and multiple beam spacings were evaluated. Depth dose curves, lateral profiles, peak‐to‐valley dose ratios (PVDR), and dose‐averaged linear energy transfer (LET) were assessed. Furthermore, evaluations of the secondary products in the valley regions were carried out and a basic example of a treatment plan in pMBRT and HeMBRT was considered. Results Compared to protons, helium ions yield a significantly improved Bragg‐peak‐to‐entrance dose ratio (BEDR) and higher PVDR at equal minibeam spacing. At the same time, due to the lower lateral scattering, dose homogenization in the target becomes more difficult for helium ions than for protons. To achieve a homogeneous target dose in HeMBRT, the minibeam spacing has to be reduced which in turn decreases the PVDR in normal tissues to values lower than those observed for protons. LET maps show up to 20%–30% higher values in the valley regions than in the peak regions for all evaluated cases. Helium ions lead to higher LET than protons at all depths, including the entrance region. However, this is compensated by a lower dose at shallow depths thanks to the improved BEDR of HeMBRT. Conclusions Helium ions might offer a good choice for minibeam radiation therapy. They provide a more pronounced spatial fractionation than protons without the possible drawbacks linked to nuclear fragmentation of heavier ions. However, biological experiments are needed to evaluate whether the higher dose heterogeneity in the target volume in HeMBRT would still lead to an efficient tumor control, as in the case of pMBRT.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: B Dose Distributionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Improving the dose distributions in minibeam radiation therapy: Helium ions vs protons

2019

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Preclinical dosimetry in proton minibeam radiation therapy: Robustness analysis and guidelines

2022

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Purpose Proton minibeam radiation therapy (pMBRT) is a new radiotherapy approach that has shown a significant increase in the therapeutic window in glioma‐bearing rats compared to conventional proton therapy. The dosimetry of pMBRT is challenging and error prone due to the submillimetric beamlet sizes used. The aim of this study was to perform a robustness analysis on the setup parameters utilized in current preclinical trials and provide guidelines for reproducible dosimetry. The results of this work are intended to guide upcoming implementations of pMBRT worldwide, as well as pave the way for future clinical implementations. Methods Monte Carlo simulations and experimental data were used to evaluate the impact of variations in setup parameters and uncertainties in collimator specifications on lateral pMBRT dose distributions. The value of each parameter was modified individually to evaluate their effect on dose distributions. Experimental dosimetry was performed by means of high‐resolution detectors, that is, radiochromic films, the IBA Razor and the Microdiamond detector. New guidelines were proposed to optimize the experimental setup in pMBRT studies and perform reproducible dosimetry. Results The sensitivity of dose distributions to uncertainties and variations in setup parameters was quantified. Quantities that define pMBRT lateral profiles (i.e., the peak‐to‐valley dose ratio [PVDR], peak and valley doses, and peak width) are significantly influenced by small‐scale fluctuations in several of those parameters. The setup implemented at the Orsay proton therapy center for pMBRT irradiation was optimized to increase PVDRs and peak symmetry. In addition, we proposed guidelines to perform accurate and reproducible dosimetry in preclinical studies. Conclusions This study revealed the importance of adopting guidelines and protocols tailored to the distinct dose delivery method and dose distributions in pMBRT. This new methodology leads to reproducible dosimetry, which is imperative in preclinical trials. The results and guidelines presented in this manuscript can ease the initiation of pMBRT investigations in other centers.

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Radiation quality correction factors for improved dosimetry in preclinical minibeam radiotherapy

Sotiropoulos

Prezado

2022

Medical Physics

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Background In reference dosimetry, radiation quality correction factors are used in order to account for changes in the detector's response among different radiation qualities, improving dosimetric accuracy. Purpose Reference dosimetry radiation quality corrections factors for the PTW microDiamond were calculated for preclinical X‐ray and proton minibeams, and their impact in dosimetric accuracy was evaluated. Methods A formalism for the calculation of radiation quality correction factors for absolute dosimetry in minibeam fields was developed. Following our formalism, radiation quality correction factors were calculated for the PTW microDiamond detector, using the Monte Carlo method. Models of the detector, and X‐ray and proton irradiation platform, were imported into the TOPAS Monte Carlo simulation toolkit. The radiation quality correction factors were calculated in the following scenarios: (i) reference dosimetry open field to minibeam center of the central peak, (ii) different positions at the minibeam profile (along the peaks and valleys direction) to the center of the central minibeam, and (iii) some representative depth positions. In addition, the radiation quality correction factors needed for the calculation of the peak‐to‐valley dose ratio at different depths were calculated. Results An important overestimation of the dose (about 10%) was found in the case of the open to minibeam field for both X‐rays and proton beams, when the correction factors were used. Smaller differences were observed in the other cases. Conclusions The usage of the PTW microDiamond detector requires radiation quality correction factors in order to be used in minibeam reference dosimetry.

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Tumor Control in RG2 Glioma-Bearing Rats: A Comparison Between Proton Minibeam Therapy and Standard Proton Therapy

Cited by 60 publications

References 7 publications

Improving the dose distributions in minibeam radiation therapy: Helium ions vs protons

Improving the dose distributions in minibeam radiation therapy: Helium ions vs protons

Preclinical dosimetry in proton minibeam radiation therapy: Robustness analysis and guidelines

Radiation quality correction factors for improved dosimetry in preclinical minibeam radiotherapy

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