ESTRO 2024 - Abstract Book

S5360

Radiobiology - Tumour biology

ESTRO 2024

sparing both in normoxia and hypoxia, compared to conventional dose rates (5 Gy/min). Preliminary data suggests that the levels of DNA double strand breaks are not significantly different between the irradiation conditions, but this and other biological end-points are being explored. Work examining FLASH PBT at higher LET is currently underway, and which will be presented.

Conclusion:

PBT with increasing LET shows enhanced biological effectiveness in HNSCC cell models due to increases in complex DNA damage, and which can be targeted with specific DNA repair inhibitors to further optimise the radiobiological response. Further studies are required and underway to explore the impact of hypoxia and FLASH on the radiobiology of PBT, necessary to contribute to more optimised treatments for HNSCC patients using PBT.

Keywords: Proton, DNA damage repair, FLASH

References:

1. Vitti, E-T., and Parsons, J.L. (2019) The radiobiological effect of proton beam therapy: Impact on DNA damage and repair. Cancers., 11 (7):946, doi: 10.3390/cancers11070946.

2. Hill, R.R., Rocha, S., and Parsons, J.L. (2022) Overcoming the impact of hypoxia in driving radiotherapy resistance in head and neck squamous cell carcinoma. Cancers. 14 (17):4130. doi: 10.3390/cancers14174130.

3. Hughes, J.R., and Parsons J.L. (2020) FLASH radiotherapy: Current knowledge and future insights using proton beam therapy. Int. J. Mol. Sci., 21 (18):E6492, doi: 10.3390/ijms21186492.

4. Carter, R.J, Nickson, C.M., Kacperek, A., Thompson, J., Hill, M.A., and Parsons, J.L. (2018) Complex DNA damage induced by high-LET α-particles and proton irradiation triggers a specific cellular DNA damage response. Int. J. Radiat. Oncol. Biol. Phys., 100 (3), 776-784, doi: 10.1016/j.ijrobp.2017.11.012. 5. Vitti, E-T., Kacperek, A., and Parsons, J.L. (2020) Targeting DNA double-strand break repair enhances radiosensitivity of HPV-positive and HPV-negative head and neck squamous cell carcinoma to photons and protons. Cancers., 12 (6):1490, doi: 10.3390/cancers12061490. 6. Carter, R.J., Nickson, C.M., Thompson, J.M., Kacperek, A., Hill, M.A., and Parsons, J.L. (2019) Characterisation of deubiquitylating enzymes involved in the cellular response to high-LET ionising radiation and complex DNA damage. Int. J. Radiat. Oncol. Biol. Phys., 104 (3), 656-665, doi: 10.1016/j.ijrobp.2019.02.053.

1013

Proffered Paper

Imaging and transcriptomic biomarkers of breast tumour response to radiotherapy in the KORTUC trial.