For ultra-high dose rate carbon-ion irradiation, comparable beam parameters induce the equivalent cell sparing (FLASH) effect.

Abstract

Recently, ultra-high dose rate (uHDR) irradiation has received attention for FLASH effect, a phenomenon in vivo that reduces normal-tissue damage without compromising antitumor efficacy compared to normal dose rate (NDR) irradiation. Such protective responses observed in vitro are referred to as cell-sparing effect. In previous studies, the cell-sparing effect was demonstrated using a carbon-ion beam scanning system. This study aimed to reproduce comparable irradiation conditions using a different machine at another facility and evaluate the cell-sparing effect. Comparable beam settings were adopted: physical dose 7 Gy, average dose rates (ADR) 100 Gy/s for uHDR and 1 Gy/s for NDR, dose-averaged linear energy transfer (LETd) 16.3 and 50 keV/μm, and identical scanning patterns. The same cell lines, Human salivary gland cell line (HSGc-C5), human dermal fibroblast (HDF), and human lung bronchial epithelial cell line (Nuli-1), were irradiated under normoxia. Colony formation assay and immunofluorescence staining of γH2AX were performed to assess cell survival and DNA damage. Comparable physical dose, ADR, and field flatness were verified by measurements. HDF and Nuli-1 showed the cell-sparing effects with increased surviving fractions and less DNA damage, which were enhanced at higher LET. In contrast, HSGc-C5 exhibited the smaller cell-sparing effect, being absent at low LET. These results were largely consistent with previous studies. To the best of current knowledge, this study is the first to indicate that the cell-sparing effect depends not on irradiation devices but on beam parameters, contributing to accelerating further FLASH research and clinical implementation of carbon-ion uHDR irradiation.