Discovery of FLASH effect conditions using compact carbon ion synchrotron opens door to safer cancer therapy

Radiation therapy is a standard cancer treatment, but it often damages not only tumors but also surrounding healthy tissues. The FLASH effect, discovered in 2014, shows that delivering radiation at dose rates exceeding 40 Gy/s can spare normal tissue while maintaining tumor control. Although FLASH effects have been reported with X-rays, electron and proton beams, evidence for similar effects using carbon ion beams -- known for their high precision and strong biological impact -- was lacking. Due to the complexity of creating a controlled uHDR environment for carbon ions, little was known about the specific conditions needed for this effect to occur.

Using a specially modified synchrotron-based system at the Osaka Heavy Ion Therapy Center, the researchers irradiated three types of human cells, two normal and one tumor, under varying conditions of oxygen concentration and linear energy transfer (LET). They found that even under normoxic (normal oxygen) conditions, uHDR carbon ion beams produced a significant "cell-sparing" effect -- an increase in the survival of normal cells compared to conventional dose rates.

This sparing effect was more prominent when using higher LET (50 keV/μm), a value typical near tumor sites in carbon therapy. Moreover, markers of DNA damage were notably lower in cells exposed to FLASH-like irradiation, suggesting a fundamental biological mechanism distinct from conventional radiation damage.

"This is the first time we have observed the cell-sparing effect with carbon ions under normoxic conditions," said Kazumasa Minami, the lead author, "it was a challenging experiment, but the results open new possibilities for safer radiotherapy." says corresponding author, Masashi Yagi.

This is the first study to demonstrate the FLASH effect under normal oxygen conditions using carbon ions, opening new possibilities for applying this technique in clinical settings. By fine-tuning irradiation parameters, such as dose, LET, and oxygen levels, researchers hope to deliver powerful cancer treatments with fewer side effects. The team envisions future studies expanding into immune response effects and tumor-specific applications.