ESTRO 2024 - Abstract Book

S5411

Radiobiology - Tumour biology

ESTRO 2024

Key NHEJ genes had the greatest impact on photon sensitivity (Lig4-/- SER = 1.8 and ATM-/- SER = 2), with genes associated with HR and complex damage having smaller effects (BRCA1-/- SER = 1.2). Wild-type cells showed RBEs of 1.1, 1.3, and 5.0 for low- and high-LET protons and alpha particles respectively. NHEJ-defective cells proved to be markedly hypersensitive across all tested LETs. Due to this hypersensitivity, the impact of NHEJ KO on survival decreases with increasing LET, due to ‘overkill’ effects. HR-defective cells had moderately increased sensitivity across all tested LETs, but, notably, the contribution of the HR pathway to survival appears independent of LET. Additionally, SERs for different genes are shown to be independent of LET.

53BP1 foci show that NHEJ-defective cells had the least DSB repair after low LET exposure, and no visible repair after high LET exposure. HR-defective cells also had slower repair kinetics, but HR’s impact is not as severe as NHEJ.

Conclusion:

Results presented here support that DNA repair capability is an important factor influencing intrinsic cellular radiosensitivity. An approximately linear correlation between RBE and LET was also shown for the tested cell models. This implies that cells which are more sensitive to photons will also be similarly more sensitive to particle therapy. Moreover, it suggests the major DNA repair pathway is NHEJ, independent of LET and, in contrast to some published data, these genetically modified cell lines show no increased dependence on HR with increasing LET. This suggests that allocation of particle therapy based on DNA repair defects may not be an effective approach to maximize the benefits of these therapies.

Keywords: High LET, CRISPR-Cas9, RBE

2429

Poster Discussion

Pioneering Change in Radiotherapy: The Transition to Biological Adaptive Radiotherapy (BART)

Daisuke Kawahara 1 , Akito Koganezawa 2 , Hikaru Yamaguchi 3 , Nobuki Imano 1 , Ikuno Nishibuchi 1 , Yuji Murakami 1

1 Hiroshima University, Radiation Oncology, Hiroshima, Japan. 2 Teikyo University, Information and Electronic Engineering, Tochigi, Japan. 3 Osaka University, Division of Health Sciences, Osaka, Japan

Purpose/Objective:

Adaptive Radiotherapy (ART) is garnering increasing attention in the realm of radiation oncology. This approach allows for the adjustment of treatment in response to daily anatomical and physiological changes, ensuring precise and optimized delivery of radiation. However, a notable limitation of current ART systems is their inability to account for the biological effects of radiation, which play a crucial role in determining therapeutic outcomes. The biological effects of radiation are multifaceted, encompassing a spectrum of cellular and tissue reactions that can influence the efficacy of the treatment. For instance, factors such as hypoxia, cellular repair mechanisms, and proliferation can significantly affect the radiosensitivity of tissues. Ignoring these effects can result in suboptimal treatment plans that either