ArticleRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2025
FLASH proton reirradiation, with or without hypofractionation, reduces chronic toxicity in the normal murine intestine, skin, and bone.
Article in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed.
- Harnessing the sparing effect of FLASH-RT: From phenomenon observation, radiophysical determinants to molecular mechanisms and synergistic strategies.Materials today. Bio · 2026Review
- Musculoskeletal and Marrow Sparing With Proton FLASH Radiation Therapy in Juvenile Mice.International journal of radiation oncology, biology, physics · 2026Article
- Preliminary mechanistic study of mitochondrial function in intestinal protection mediated by high-energy X-ray FLASH radiotherapy.Radiation oncology (London, England) · 2026Article
- Investigating the oxygen dependence of FLASH-RT using electron paramagnetic resonance imaging.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2026Article
- FLASH radiotherapy as an emerging paradigm in radioimmunotherapy: biological rationale, preclinical evidence, and translational roadmap.Frontiers in immunology · 2026Review
- Mechanisms, challenges and opportunities for FLASH radiotherapy in cancer.Nature reviews. Cancer · 2026Review
- FLASH effect is diminished by daily fractionation of electron RT in mouse skin.Physics in medicine and biology · 2025Article
- Factors Influencing the Biological Effects of FLASH Irradiation.Antioxidants (Basel, Switzerland) · 2025Review
- Tissue-specific iron levels modulate lipid peroxidation and the FLASH radiotherapy effect.Cell death & disease · 2025Article
- Comparative metabolomic analysis of human lung slices (hu-PCLS) exposed to either standard or FLASH protons: a pilot study.Radiation oncology (London, England) · 2025Article
- Physicochemical indication of the FLASH effect from shoot-through proton pencil beam scanning parameters delivered under ultra-high dose rates.Physics in medicine and biology · 2025Article
- Fixation method influences FLASH skin sparing in an in vivo leg model.Acta oncologica (Stockholm, Sweden) · 2025Article
- Commissioning of a 142.4 MeV ultra-high dose rate (UHDR) proton beamline in a synchrotron-based proton therapy system.Medical physics · 2025Article
- Reirradiation: Standards, challenges, and patient-focused strategies across tumor types.CA: a cancer journal for cliniciansReview
- Towards Clinical Translation: Establishing Optimal Dose and Dose-Rate Parameters for the FLASH Skin-Sparing Effect.Dose-response : a publication of International Hormesis SocietyArticle
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Abstract
background and purposeThe normal tissue sparing afforded by FLASH radiotherapy is being intensely investigated for potential clinical translation. Here, we studied the effects of FLASH proton radiotherapy (F-PRT) in the reirradiation setting, with or without hypofractionation. Chronic toxicities in three murine models of normal tissue toxicity including the intestine, skin, and bone were investigated. MATERIALS AND
methodsIn studies of the intestine, single-dose irradiation was performed with 12 Gy of standard proton RT (S-PRT), followed by a second dose of 12 Gy of F-PRT or S-PRT. Additionally, a hypofractionation scheme was applied in the reirradiation setting (3 x 6.4 Gy of F-PRT or S-PRT, given every 48 hrs). In studies of skin/bone of the murine leg, 15 Gy of S-PRT was followed by hypofractionated reirradiation with F-PRT or S-PRT (3 x 11 Gy).
resultsCompared to reirradiation with S-PRT, F-PRT induced less intestinal fibrosis and collagen deposition that was accompanied by significantly increased survival rate, demonstrating its protective effects on intestinal tissues in the reirradiation setting. In previously irradiated leg tissues, reirradiation with hypofractionated F-PRT created transient dermatitis that fully resolved in contrast to reirradiation with hypofractionated S-PRT. Lymphedema was also alleviated after a second course of radiation with F-PRT, along with significant reductions in the accumulation of fibrous connective tissue in the skin, compared to mice reirradiated with S-PRT. The delivery of a second course of fractionated S-PRT induced tibial fractures in 83.3% of the mice, whereas only 20% of mice reirradiated with F-PRT presented with fractures.
conclusionThese studies provide the first evidence of the sparing effects of F-PRT in the setting of hypofractionated reirradiation. The results support FLASH as highly relevant to the reirradiation regimen where it exhibits significant potential to minimize chronic complications for patients undergoing RT.
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