Combining FLASH and spatially fractionated radiation therapy: The best of both worlds

Schneider, Tim; Fernández-Palomo, Cristian; Bertho, Annaïg; Fazzari, Jennifer; Iturri, Lorea; Martin, Olga A.; Trappetti, Verdiana; Djonov, Valentin; Prezado, Yolanda

doi:10.1016/j.radonc.2022.08.004

Cited by 12 publications

(9 citation statements)

References 125 publications

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“…A novel partial irradiation technique, spatially fractionated radiation therapy (SFRT), can also induce an antitumor immune response. SFRT can deliver a high dose to a large irradiation field that is segmented into several small units with steep dose gradients, which lead to reduce the normal tissue toxicity ( 208 – 211 ). In the study of Johnsrud et al.…”

Section: Partial Irradiationmentioning

confidence: 99%

Application of individualized multimodal radiotherapy combined with immunotherapy in metastatic tumors

Jiang

Wang

et al. 2023

Front. Immunol.

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Radiotherapy is one of the mainstays of cancer treatment. More than half of cancer patients receive radiation therapy. In addition to the well-known direct tumoricidal effect, radiotherapy has immunomodulatory properties. When combined with immunotherapy, radiotherapy, especially high-dose radiotherapy (HDRT), exert superior systemic effects on distal and unirradiated tumors, which is called abscopal effect. However, these effects are not always effective for cancer patients. Therefore, many studies have focused on exploring the optimized radiotherapy regimens to further enhance the antitumor immunity of HDRT and reduce its immunosuppressive effect. Several studies have shown that low-dose radiotherapy (LDRT) can effectively reprogram the tumor microenvironment, thereby potentially overcoming the immunosuppressive stroma induced by HDRT. However, bridging the gap between preclinical commitment and effective clinical delivery is challenging. In this review, we summarized the existing studies supporting the combined use of HDRT and LDRT to synergistically enhance antitumor immunity, and provided ideas for the individualized clinical application of multimodal radiotherapy (HDRT+LDRT) combined with immunotherapy.

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Section: Partial Irradiationmentioning

confidence: 99%

Application of individualized multimodal radiotherapy combined with immunotherapy in metastatic tumors

Jiang

Wang

et al. 2023

Front. Immunol.

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“…Spatially-fractionated radiotherapy (SFRT) and FLASH RT delivered at ultra-high dose rates (UHDRs) are two new non-standard radiotherapy techniques of great interest in modern oncology due to the distinct normal-tissue-sparing effects they can each elicit. Recent discussion has arisen on a possible synergy between the two techniques which could potentially result in the increase of their individual therapeutic windows (Schneider et al 2022). However, research on potential delivery methods to achieve the two tissue-sparing effects in deep-seated tumours simultaneously is needed.…”

Section: Introductionmentioning

confidence: 99%

“…Sub-second FLASH irradiations synergize well with spatially-fractionated techniques, given that loss of spatial fractionation often occurs as a result of organ motion due to treatment times longer than physiological motion. The normal tissue-sparing effects of FLASH RT and SFRT are thought to occur through different biological mechanisms (Schneider et al 2022) and thus have different physical and delivery requirements; as an example, SFRT does not seem to have the same requirements on the beam time structure, threshold dose, irradiation time, and tissue oxygen concentration that FLASH radiotherapy does (Dilmanian et al 2003, Adrian et al 2020, Vozenin et al 2020, Wilson et al 2020. Therefore, future studies using sources that are capable of spatially-fractionated and open beam UHDR irradiations could help determine the potential for combining the techniques and determining to what degree each technique contributes should the effects synergize (Wright et al 2021).…”

Section: Introductionmentioning

confidence: 99%

Mini-GRID radiotherapy on the CLEAR very-high-energy electron beamline: collimator optimization, film dosimetry, and Monte Carlo simulations

Clements,

Esplen,

Bateman

et al. 2024

Phys. Med. Biol.

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Objective: Spatially-fractionated radiotherapy (SFRT) delivered with avery-high-energy electron (VHEE) beam and a mini-GRID collimator was investigatedto achieve synergistic normal tissue-sparing through spatial fractionation and theFLASH effect.Approach: A tungsten mini-GRID collimator for delivering VHEE SFRT wasoptimized using Monte Carlo (MC) simulations. Peak-to-valley dose ratios (PVDRs),depths of convergence (DoCs, PVDR≤1.1), and peak and valley doses in a waterphantom from a simulated 150 MeV VHEE source were evaluated. Collimatorthickness, hole width, and septal width were varied to determine an optimal valuefor each parameter that maximized PVDR and DoC. The optimized collimator (20 mm thick rectangular prism with a 15 mm×15 mm face with a 7×7 array of 0.5mm holes separated by 1.1 mm septa) was 3D-printed and used for VHEE irradiationswith the CERN Linear Electron Accelerator for Research (CLEAR) beam. Open beamand mini-GRID irradiations were performed at 140, 175, and 200 MeV and dose wasrecorded with radiochromic films in a water tank. PVDR, central-axis (CAX) andvalley dose rates and DoCs were evaluated.Main results: Films demonstrated peak and valley dose rates on the order of 100sof MGy/s, which could promote FLASH-sparing effects. Across the three energies,PVDRs of 2-4 at 13 mm depth and DoCs between 39-47 mm were achieved. Openbeam and mini-GRID MC simulations were run to replicate the film results at 200MeV. For the mini-GRID irradiations, the film CAX dose was on average 15% higher,the film valley dose was 28% higher, and the film PVDR was 15% lower than calculatedby MC.Significance: Ultimately, the PVDRs and DoCs were determined to be too low fora significant potential for SFRT tissue-sparing effects to be present, particularly at depth. Further beam delivery optimization and investigations of new means of spatialfractionation are warranted.

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“…MRT exploits the dose-volume effect [7,8], a phenomenon in which mature biological tissues tolerate high microbeam doses in the order of hundreds of Gy better than broad beam doses of only a few Gy. MRT has shown remarkable results in numerous preclinical studies compared to conventional radiotherapy, thanks to increased tolerance of healthy tissues and increased effectiveness in limiting tumour development [8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Synchrotron x-ray spectra characterisation for radiation therapy applications at the ESRF - ID17 biomedical beamline

Di Manici,

Reyes-Herrera,

Day

et al. 2024

Phys. Scr.

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Objective: Radiation therapy requires reliable dosimetry protocols to deliver successful treatments with high accuracy and precision. In this context, accurate knowledge of the beam’s energy spectra is mandatory. The goal of this study was to validate the synchrotron X-ray spectrum of the ID17 beamline at the European Synchrotron Radiation Facility (ESRF). The modification of the synchrotron storage ring and beamline in recent years necessitates a new characterisation of the radiation spectra of the ID17 beamline. The validated spectra will be a starting point for possible future clinical applications.Approach: The half value layer method was used to measure the attenuation of the X-ray spectrum in Al and Cu. Experimental data was validated against theoretical data produced using OASYS; an in-house developed software for calculating beamline spectra. Two different spectral configurations, “conventional” and “clinical”, were investigated. The characterised spectra were used to perform dosimetric validation of depth dose profiles measured in a water-equivalent phantom. The dose profile was measured using two different detectors and compared with calculations generated using two different Monte Carlo algorithms.Main results: The results showed good agreement between measured and predicted half value layers, with differences of less than 1%. Excellent agreement to within 3% was obtained, an agreement that satisfies the requirements in conventional radiotherapy for approvable treatment planning.Significance: Accurate spectra have been defined and validated for the ESRF – ID17 Biomedical beamline. The validated spectra can be used as input for future dosimetric studies and treatment planning systems in the context of preclinical studies and possible future clinical trials.

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Combining FLASH and spatially fractionated radiation therapy: The best of both worlds

Cited by 12 publications

References 125 publications

Application of individualized multimodal radiotherapy combined with immunotherapy in metastatic tumors

Application of individualized multimodal radiotherapy combined with immunotherapy in metastatic tumors

Mini-GRID radiotherapy on the CLEAR very-high-energy electron beamline: collimator optimization, film dosimetry, and Monte Carlo simulations

Synchrotron x-ray spectra characterisation for radiation therapy applications at the ESRF - ID17 biomedical beamline

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