ESTRO 2024 - Abstract Book

S5309 ESTRO 2024 TSR in irradiated rats compared with Control rats. In addition, t\The FLASH-95 rats had increased ASR compared with Control rats. In MWM acquisition and reversal, the Conv and FLASH-60 rats had reduced path efficiency compared with Controls with the FLASH-95 group in between. For MWM shift and shift reversal all irradiated rats had longer latencies and reduced path efficiencies. In CWM-A all irradiated rats had longer latencies and more errors than Controls, but there were no differences in CWM-B. There were no differences in the novelty tests or RWM. No cognitive sparing was observed for FLASH in this experiment. Experiment 3: For adult rats, all irradiated groups had deficits in the CWM-A. Decreased center ambulation in the open-field, increased latency on day-1 of RWM, and deficits in CWM-B were observed in irradiated groups, except the 5 Gy FLASH group which showed sparing. ASR and TSR were reduced in the 8 Gy FLASH group and day-2 latencies in the RWM were increased in FLASH groups compared with controls. There were no effects on prepulse trials of ASR or TSR, or on NOR, MWM, or conditioned freezing. The 5 Gy FLASH group showed cognitive sparing and these data reveal that FLASH sparing of brain function occurs at intermediate exposure levels. Radiobiology - Normal tissue radiobiology

Conclusion:

Proton radiotherapy is an important step forward toward reducing adverse cognitive effects, but the FLASH effect occurs within an intermediate dose level. The results suggest that the striatum, prefrontal cortex, and hippocampus and the cognitive effects associated with them are radiosensitive in rats. Future studies should examine FLASH dose rates below 18 Gy to identify where the FLASH effect is most pronounced.

Keywords: protons, Flash effect, cognitive

References:

1. Coomans, M.B., et al., Treatment of cognitive deficits in brain tumour patients: current status and future directions. Curr Opin Oncol, 2019. 31(6): p. 540-547.

2. Greenberger, B.A., et al., Clinical outcomes and late endocrine, neurocognitive, and visual profiles of proton radiation for pediatric low-grade gliomas. Int J Radiat Oncol Biol Phys, 2014. 89(5): p. 1060-1068.

3. Ma, T.M., et al., A prospective evaluation of hippocampal radiation dose volume effects and memory deficits following cranial irradiation. Radiother Oncol, 2017. 125(2): p. 234-240.

4. Ventura, L.M., et al., Executive functioning, academic skills, and quality of life in pediatric patients with brain tumors post-proton radiation therapy. J Neurooncol, 2018. 137(1): p. 119-126.

5. Carbonara, R., et al., Proton versus Photon Radiotherapy for Pediatric Central Nervous System Malignancies: A Systematic Review and Meta-Analysis of Dosimetric Comparison Studies. Journal of oncology, 2019. 2019: p. 5879723-5879723.

6. Slater, J.D., Clinical applications of proton radiation treatment at Loma Linda University: review of a fifteen year experience. Technol Cancer Res Treat, 2006. 5(2): p. 81-9.

7. Kahalley, L.S., et al., Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma. J Clin Oncol, 2020. 38(5): p. 454-461.

8. Alaghband, Y., et al., Uncovering the Protective Neurologic Mechanisms of Hypofractionated FLASH Radiotherapy. Cancer Res Commun, 2023. 3(4): p. 725-737.