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Updated: Jan 14, 2026
Ischemic Tissue Injury in the Dorsal Skinfold Chamber of the Mouse: A Skin Flap Model to Investigate Acute Persistent Ischemia
Published on: November 17, 2014
Fractionation increasingly reduces FLASH sparing for acute murine skin damage
Line Kristensen1, Sky Rohrer2, Jacob Graversen Johansen2
1Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark; Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Fractionation significantly reduces the normal tissue-sparing effect of FLASH radiotherapy. While a single dose shows a substantial effect, this benefit diminishes with multiple fractions, suggesting FLASH may be most effective in hypofractionated treatments.
Area of Science:
- Radiation oncology
- Preclinical research
- Cancer therapy
Background:
- FLASH radiotherapy demonstrates normal tissue sparing in preclinical models.
- Most studies focus on single-fraction irradiations, leaving the impact of fractionation unclear.
- Understanding fractionation's effect is crucial for clinical translation of FLASH therapy.
Purpose of the Study:
- To compare the tissue-sparing effects of FLASH irradiation on acute skin toxicity.
- To evaluate FLASH sparing across single-fraction, four-fraction, and eight-fraction schemes.
- To determine the impact of fractionation on FLASH's normal tissue-sparing capabilities.
Main Methods:
- Acute skin toxicity was assessed in mice following conventional dose rate (CONV) and FLASH irradiation.
- Irradiation schemes included single, four, and eight fractions using a 16 MeV electron beam.
- Doses ranged from 24.5 to 89.9 Gy, with toxicity quantified daily for 28 days post-treatment.
Main Results:
- A significant FLASH tissue-sparing effect was observed in single-fraction irradiations (Dose Modification Ratio [DMR] = 1.41).
- The sparing effect was reduced by approximately half in four-fraction schemes (DMR = 1.18).
- The tissue-sparing effect was markedly reduced and nonsignificant in eight-fraction schemes (DMR = 1.05).
Conclusions:
- Fractionation progressively diminishes the acute skin-sparing advantage of FLASH radiotherapy.
- An 18% sparing effect persisted with four fractions, but only a nonsignificant 5% was observed with eight fractions.
- Clinical application of FLASH radiotherapy may be most beneficial in highly hypofractionated treatment protocols.
