ArticleCancers2021
FLASH Proton Pencil Beam Scanning Irradiation Minimizes Radiation-Induced Leg Contracture and Skin Toxicity in Mice.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 5 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
127 citing papers in PubMed, 5 syntheses or guidelines pooled it, 218 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 FLASH effect-an evaluation of preclinical studies of ultra-high dose rate radiotherapy.Frontiers in oncology · 2024Pooled 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
- X‑ray FLASH RT inhibits lung cancer bone metastasis via activating CD4⁺ T-cell‑mediated antitumor immunity with modulation of Th17 cell response.Oncoimmunology · 2026Article
- 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
- Time-resolved point dosimetry for spread-out Bragg-peak proton FLASH using fibre-coupled scintillators.Medical physics · 2026Article
- Use of apertures in single-energy pristine Bragg peak FLASH radiotherapy.Journal of applied clinical medical physics · 2026Article
- Research progresses on FLASH radiotherapy and its application for the treatment of digestive system tumors.Discover oncology · 2026Review
- Investigating the FLASH Effect in a Rat Brain Organotypic Model With a Novel High-Energy Electron Beam.International journal of radiation oncology, biology, physics · 2026Article
- 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
- Biological effects of conventional and ultra high dose rate radiation in human cells.Scientific reports · 2026Article
- FLASH radiotherapy as an emerging paradigm in radioimmunotherapy: biological rationale, preclinical evidence, and translational roadmap.Frontiers in immunology · 2026Review
- FLASH radiotherapy and immunotherapy synergy: mechanisms, strategies, and clinical translation prospects.Frontiers in immunology · 2026Review
- The potential and risks of FLASH radiotherapy in pediatric patients.Neuro-oncology pediatrics · 2026Review
- Microenvironmental remodeling in FLASH radiotherapy.Frontiers in cell and developmental biology · 2026Review
- Combining advanced radiotherapy techniques and immunotherapy: immunomodulatory mechanisms and clinical prospects.Frontiers in immunology · 2026Review
67 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
11 authors at 3 institutions in 1 country.
Funding
Abstract
Ultra-high dose rate radiation has been reported to produce a more favorable toxicity and tumor control profile compared to conventional dose rates that are used for patient treatment. So far, the so-called FLASH effect has been validated for electron, photon and scattered proton beam, but not yet for proton pencil beam scanning (PBS). Because PBS is the state-of-the-art delivery modality for proton therapy and constitutes a wide and growing installation base, we determined the benefit of FLASH PBS on skin and soft tissue toxicity. Using a pencil beam scanning nozzle and the plateau region of a 250 MeV proton beam, a uniform physical dose of 35 Gy (toxicity study) or 15 Gy (tumor control study) was delivered to the right hind leg of mice at various dose rates: Sham, Conventional (Conv, 1 Gy/s), Flash60 (57 Gy/s) and Flash115 (115 Gy/s). Acute radiation effects were quantified by measurements of plasma and skin levels of TGF-β1 and skin toxicity scoring. Delayed irradiation response was defined by hind leg contracture as a surrogate of irradiation-induced skin and soft tissue toxicity and by plasma levels of 13 different cytokines (CXCL1, CXCL10, Eotaxin, IL1-beta, IL-6, MCP-1, Mip1alpha, TNF-alpha, TNF-beta, VEGF, G-CSF, GM-CSF and TGF- β1). Plasma and skin levels of TGF-β1, skin toxicity and leg contracture were all significantly decreased in FLASH compared to Conv groups of mice. FLASH and Conv PBS had similar efficacy with regards to growth control of MOC1 and MOC2 head and neck cancer cells transplanted into syngeneic, immunocompetent mice. These results demonstrate consistent delivery of FLASH PBS radiation from 1 to 115 Gy/s in a clinical gantry. Radiation response following delivery of 35 Gy indicates potential benefits of FLASH versus conventional PBS that are related to skin and soft tissue toxicity.
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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.