ArticleCancer research2021
FLASH Proton Radiotherapy Spares Normal Epithelial and Mesenchymal Tissues While Preserving Sarcoma Response.
Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
115 citing papers in PubMed, 4 syntheses or guidelines pooled it, 179 citations in OpenAlex.
- Global clinical landscape and multidisciplinary translational frontiers of FLASH radiotherapy: a systematic review and visualized bibliometric mapping based on WoSCC and PubMed (2014-2025).Frontiers in medicine · 2026Pooled it
- Impact assessment of current knowledge gaps and mitigation strategies in clinical FLASH proton therapy through a systematic review.Frontiers in oncology · 2025Pooled it
- The current status of FLASH particle therapy: a systematic review.Physical and engineering sciences in medicine · 2023Pooled it
- Examining the Occurrence of the FLASH Effect in Animal Models: A Systematic Review and Meta-Analysis of Ultra-High Dose Rate Proton or Carbon Ion Irradiation.Technology in cancer research & treatmentPooled it
- Harnessing Particle Ions for FLASH Radiotherapy.Cells · 2026Review
- Harnessing the sparing effect of FLASH-RT: From phenomenon observation, radiophysical determinants to molecular mechanisms and synergistic strategies.Materials today. Bio · 2026Review
- PROTAC-based nanoassemblies targeting BRD4 for potentiate FLASH radiosensitization therapy.Materials today. Bio · 2026Article
- From developmental origins to relapse: molecular and therapeutic insights in medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Review
- Article
- Deciphering Ultra-High Dose Rate Irradiation withAntioxidants (Basel, Switzerland) · 2026Article
- Musculoskeletal and Marrow Sparing With Proton FLASH Radiation Therapy in Juvenile Mice.International journal of radiation oncology, biology, physics · 2026Article
- A Novel Focal Duodenal Radiation Injury Model Reveals Dose-, Time-, and Spatially Dependent Microbiome Perturbations After Radiation Injury.International journal of radiation oncology, biology, physics · 2026Article
- One-year follow-up after fractionated ultra-high-dose-rate FLASH radiotherapy in patient with extramammary Paget disease of the scrotum.Precision radiation oncology · 2026Article
- Review
- FLASH radiotherapy preserves systemic and tissue homeostasis while maintaining antitumor efficacy.BMC medicine · 2026Article
- Is Ultrahigh Dose Rate Critical for the Effectiveness of Microbeam Radiation Therapy in a Broad-Beam Combined Treatment?Advances in radiation oncology · 2026Article
- Ionizing radiation: molecular mechanisms, biological effects, and therapeutic targets.Molecular biomedicine · 2026Review
- FLASH radiotherapy as an emerging paradigm in radioimmunotherapy: biological rationale, preclinical evidence, and translational roadmap.Frontiers in immunology · 2026Review
- Systematic analysis of biological endpoint variability and implications for quantitative modeling of the FLASH sparing effect.Physics and imaging in radiation oncology · 2026Review
- Microenvironmental remodeling in FLASH radiotherapy.Frontiers in cell and developmental biology · 2026Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 2 institutions in 3 countries.
Funding
Abstract
In studies of electron and proton radiotherapy, ultrahigh dose rates of FLASH radiotherapy appear to produce fewer toxicities than standard dose rates while maintaining local tumor control. FLASH-proton radiotherapy (F-PRT) brings the spatial advantages of PRT to FLASH dose rates (>40 Gy/second), making it important to understand if and how F-PRT spares normal tissues while providing antitumor efficacy that is equivalent to standard-proton radiotherapy (S-PRT). Here we studied PRT damage to skin and mesenchymal tissues of muscle and bone and found that F-PRT of the C57BL/6 murine hind leg produced fewer severe toxicities leading to death or requiring euthanasia than S-PRT of the same dose. RNA-seq analyses of murine skin and bone revealed pathways upregulated by S-PRT yet unaltered by F-PRT, such as apoptosis signaling and keratinocyte differentiation in skin, as well as osteoclast differentiation and chondrocyte development in bone. Corroborating these findings, F-PRT reduced skin injury, stem cell depletion, and inflammation, mitigated late effects including lymphedema, and decreased histopathologically detected myofiber atrophy, bone resorption, hair follicle atrophy, and epidermal hyperplasia. F-PRT was equipotent to S-PRT in control of two murine sarcoma models, including at an orthotopic intramuscular site, thereby establishing its relevance to mesenchymal cancers. Finally, S-PRT produced greater increases in TGFβ1 in murine skin and the skin of canines enrolled in a phase I study of F-PRT versus S-PRT. Collectively, these data provide novel insights into F-PRT-mediated tissue sparing and support its ongoing investigation in applications that would benefit from this sparing of skin and mesenchymal tissues. SIGNIFICANCE: These findings will spur investigation of FLASH radiotherapy in sarcoma and additional cancers where mesenchymal tissues are at risk, including head and neck cancer, breast cancer, and pelvic malignancies.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.