3043 - Radiobiology of Image-Guided Radiotherapy: In Vitro<em> </em>Radiosensitivity of Lung Cancer following Computed Tomography Exposure

05:00pm - 06:00pm PT

Hall F

Screen: 2

POSTER

Presenter(s)

Rana El-Hassan, MS - American University of Beirut, Beirut, Beyrouth

R. El-Hassan¹, C. Feghaly², H. Bou Hadir², R. Challita¹, V. Manouguian¹, T. A. Eid², W. Abou-Kheir¹, and L. Bodgi²; ¹American University of Beirut, Beirut, Lebanon, ²American University of Beirut Medical Center, Beirut, Lebanon

Purpose/Objective(s):

Modern radiotherapy (RT) systems incorporate image-guided and adaptive techniques, involving daily computed tomography (CT) scans before each RT session to adjust treatment plans in real time based on tumor size or anatomical changes.

Radiation from imaging is commonly considered clinically negligible compared to therapeutic doses. However, emerging evidence shows that even low doses can cause harmful effects, particularly when followed by a high dose. The time interval between a low CT dose and a higher RT dose may significantly influence this effect.

We hypothesize that undergoing CT scans before RT may radioprotect through an adaptive response or radiosensitize cells depending on both the time interval between both irradiations and the intrinsic radiosensitivity of cells.

Materials/Methods:

Two human lung cancer cell lines and one normal skin fibroblast cell line were subjected to: (a) single low-dose radiation (0.1 or 0.2 Gy) at low energy ([i] 50 kV, 2 mA, dose rate (DR) = 3 cGy/min; [ii] 50 kV, 20 mA, DR = 30 cGy/min) or high energy ([iii] 225 kV, 13.3 mA, DR = 260 cGy/min), (b) a single high-energy 2 Gy dose, or (c) a low dose followed by 2 Gy, with time intervals (?t = 1-20 min).

Cellular radiosensitivity was determined through clonogenic and micronuclei (MN) assays. DNA double-strand break (DSB) repair kinetics were evaluated using immunofluorescence, targeting key protein markers pATM and ?H2AX before and after irradiation.

Results:

Cells treated with a low dose followed by a high dose had a significantly lower surviving fraction compared to the sum of single doses, indicating that sequential irradiation has a more detrimental effect on cell survival than an additive response, with the time interval between exposures possibly playing a critical role in this effect.

Immunofluorescence targeting pATM and ?H2AX DSB repair biomarkers confirmed these results. Cells subjected to low-dose irradiation showed significant unrepaired DNA DSBs 24h after exposure. When a low dose was followed by a 2 Gy dose with a 1-min interval, ?H2AX foci were significantly higher compared to the 2 Gy dose or the sum of separate doses. Similarly, MN formation increased 24h post-irradiation, whether cells were treated with single low or high doses or a combination of doses. In cells treated with combination doses, a decrease in pATM foci was observed 10 min and 1h post-irradiation, suggesting that CT exposure impairs DNA DSB repair.

Conclusion:

Our results indicate that the time interval between a low dose followed by a high dose can impact the DNA damage response. This has potential clinical implications for adaptive RT, especially when administered daily. It emphasizes the importance of considering both imaging exposure and the time interval in RT planning.

Abstract 3043 - Table 1

Condition	Dose (Gy)	Energy & Parameters			Time Interval (min)
		Voltage (kV)	Current (mA)	DR (cGy/min)
Low Dose	0.1	50	2	3	?t = 1-20
	0.2	50	20	30
High Dose	2	225	13.3	260
Combination	0.1 + ?t + 2	Same parameters as above
	0.2 + ?t + 2