Photon FLASH spares radiation-induced changes in cardiac function, remodelling and arrythmia in a preclinical model.
Ghita-Pettigrew M., Brown KH., Kerr BN., Walls GM., Verginadis II., Adrian G., Petersson K., McMahon SJ., Butterworth KT.
INTRODUCTION: Preclinical studies have demonstrated the ability of FLASH irradiation to expand the therapeutic window by sparing normal tissues. The heart is a critical organ at risk in patients receiving radiotherapy for thoracic cancers. This study aimed to quantify the cardiac sparing effects of photon FLASH delivered as single (FLASH) or FLASH split dose (FSD) exposures. METHODS: Female C57BL/6 mice were irradiated with 18.5 ± 0.6 Gy delivered to the whole heart using a FLASH-SARRP (Xstrahl Life Sciences, UK) at a dose rate of 85.6 ± 1.6 Gy/s (isocentre dose rate 75.9 ± 1.5 Gy/s). Comparative studies were undertaken using 18.6 ± 0.4 Gy delivered using two consecutive pulses (FSD) at an average dose rate of 2.8 ± 0.9 Gy/s, and with 20.1 ± 0.5 Gy using a conventional SARRP at a dose rate of 3.4 ± 0.2 Gy/min (CONV). Transthoracic echocardiography was performed at 10 and 30 weeks with supporting histology and analysis of serum biomarkers 30 weeks post irradiation. RESULTS: In comparison to CONV and FSD exposures, FLASH significantly reduced radiation-induced loss of cardiac function, cardiac remodelling and arrythmia 30 weeks after irradiation. These observations were supported by reduced myocardial fibrosis, cardiac injury biomarkers and inflammatory cytokines. CONCLUSIONS: This study highlights the ability of photon FLASH to preserve cardiac function and structure from radiation damage with the level of sparing dependent on average dose rate and beam structure.