Time Gaps May Be Critical Parameters When Sparing Skin During FLASH Radiation Therapy

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Researchers have demonstrated that, in preclinical models, multiple beams and intervals in delivery during FLASH radiation therapy may compromise the skin-sparing effects of the technique, according to a novel study published by Mascia et al in the International Journal of Radiation Oncology • Biology • Physics.


FLASH is an experimental mode of delivering radiation therapy that can be delivered to patients with cancer in less than 1 second—and may be over 100 times faster than conventional radiation therapy.

Previous studies have indicated that FLASH may be safer than standard forms of radiation therapy and, in many cases, may cause fewer side effects such as skin irritation or burning. 

“FLASH proton pencil-beam scanning has shown a reduction in skin toxicity for preclinical models when delivered in a single, uninterrupted high dose,” highlighted senior study author Mathieu Sertorio, PhD, a member of the Basic Science Research program at the University of Cincinnati Cancer Center. “However, for treatment of patients, multiple beams are required to diminish the exposure of normal tissue to radiation and to make sure the entire area identified for treatment is targeted. The administration of these beams [is] separated by minutes to allow patient and equipment repositioning,” he added.

Study Methods and Results

In the new study, the researchers delivered a particular radiation dose of FLASH therapy in either a single beam or multiple beams in one area of a mouse model and observed skin tissue over the course of 16 weeks.

“The treatment was delivered as one, two, or three equal beams with an interruption of 2 minutes simulating the clinical experience of patients,” explained Dr. Sertorio.

The researchers found that the single-beam delivery showed a maximum benefit to the skin; however, when it was interrupted for 2 minutes and then readministered in the same area, it reduced the FLASH skin-sparing effect. After two interruptions, the skin tissue–sparing effect was further eliminated.


“Our results indicate that the FLASH skin-sparing effect in areas of beam overlap were diminished by multiple beams as opposed to single beams,” Dr. Sertorio emphasized. “This study suggests the number of beams and the spatial arrangement of those beams are important parameters for FLASH studies. Furthermore, the effect of multibeam delivery is likely different for different organs of interest,” he suggested.

"This study is important because it informs the clinical translation of FLASH [radiation] therapy, with respect to beam delivery modalities, treatment planning, and radiation prescriptions,” underscored lead study author Anthony Mascia, PhD, of the Cincinnati Children’s Hospital Medical Center. “We need to identify where FLASH works and where FLASH doesn't work to move forward,” he concluded.

Disclosure: For full disclosures of the study authors, visit

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