Tinganelli Walter, Puspitasari-Kokko Anggraeini, Sokol Olga, Helm Alexander, Simoniello Palma, Schuy Christoph, Lerchl Sylvie, Eckert Denise, Oppermann Julius, Rehm Anna, Janssen Stefan, Engel Denise, Moeller Ralf, Romano Rossana, Horst Felix, Boscolo Daria, Fournier Claudia, Durante Marco, Weber Uli
GSI Helmholtzzentrum für Schwerionenforschung, Biophysics Department, Darmstadt, Germany.
Department of Research and Development, Holland PTC, Delft, The Netherlands.
Int J Radiat Oncol Biol Phys. 2025 Apr 1;121(5):1282-1292. doi: 10.1016/j.ijrobp.2024.11.089. Epub 2024 Nov 26.
In recent years, ultra-high dose rate (UHDR) irradiation has emerged as a promising innovative approach to cancer treatment. Characteristic feature of this regimen, commonly referred to as FLASH effect, demonstrated primarily for electrons, photons, or protons, is the improved normal tissue sparing, whereas the tumor control is similar to the one of the conventional dose-rate (CDR) treatments. The FLASH mechanism is, however, unknown. One major question is whether this effect is maintained when using densely ionizing (high-LET) heavy nuclei.
Here, we report the effects of 20 Gy UHDR heavy ion irradiation in clinically relevant conditions, ie, at high-LET in the spread-out Bragg peak of a C beam using an osteosarcoma mouse model.
We show that UHDR irradiation was less toxic in the normal tissue compared with CDR while maintaining tumor control. The immune activation was also comparable in UHDR and CDR groups. Both UHDR and CDR exposures steered the metagenome toward a balanced state.
These results suggest that the UHDR irradiations can improve the safety and effectiveness of heavy ion therapy, and provide a crucial benchmark for current mechanistic FLASH models. However, additional experiments are needed to validate these findings across other animal and tumor models.
近年来，超高剂量率（UHDR）辐照已成为一种有前景的癌症治疗创新方法。这种治疗方案的特征，通常称为FLASH效应，主要在电子、光子或质子照射中得到证实，即能更好地保护正常组织，而肿瘤控制情况与传统剂量率（CDR）治疗相似。然而，FLASH机制尚不清楚。一个主要问题是，当使用高电离密度（高传能线密度，high-LET）的重离子时，这种效应是否依然存在。
在此，我们报告了在临床相关条件下，即使用骨肉瘤小鼠模型，在碳离子束扩展布拉格峰的高传能线密度条件下，20 Gy超高剂量率重离子辐照的效果。
我们发现，与传统剂量率辐照相比，超高剂量率辐照对正常组织的毒性更小，同时能维持肿瘤控制效果。超高剂量率组和传统剂量率组的免疫激活情况也相当。超高剂量率辐照和传统剂量率辐照均使宏基因组趋向平衡状态。
这些结果表明，超高剂量率辐照可提高重离子治疗的安全性和有效性，并为当前的FLASH效应机制模型提供关键基准。然而，需要更多实验在其他动物和肿瘤模型中验证这些发现。
