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A Study of Indirect Apoptotic Death by Vascular Damage On Cell Survival After Single-Fraction Radiotherapy by Using An Improved Cellular Automata Model

D Kawahara1*, L WU2, Y Nagata1, Y Watanabe2, (1) ,Hiroshima University, Hiroshima, JP, (2) Minnesota University, Minneapolis, MN

Presentations

PO-GePV-T-441 (Sunday, 7/25/2021)   [Eastern Time (GMT-4)]

Purpose: To investigate the effects of indirect apoptotic cell death due to vascular damage by a single large dose with an improved cellular automata (CA) model.

Methods: The tumor growth process was simulated by considering the oxygen and nutrients supplied from the blood vessels. The cell damage process was simulated by considering the direct radiation damage with the LQ-model and the indirect apoptotic death by the vessel damage. The radiation caused increased permeation of plasma protein through the blood vessel or the breakdown of the vasculature. The amount of oxygen in cancer cells lead to a change in radiation sensitivity of cancer cells and tumor growth rate after irradiation. The indirect apoptotic death was evaluated with a single dose of 6 to 24 Gy on 100 day after the irradiation. The tumor control probability (TCP) was evaluated by varying the probability of apoptotic death, Pᵃᵖᵒᵖ, the threshold of the oxygen level for indirect apoptotic death, Oᵗʰʳᵉ, and the average oxygen level, Oᵃᵛᵛᵍ in cancer cells.

Results: The apoptotic death increased with a higher Oᵗʰʳᵉ and a higher Pᵃᵖᵒᵖ. Consequently, the TCP increased. TCP as a function of Oᵃᵛᵍ exhibited the minimum at a certain Oᵃᵛᵍ. The apoptosis increased as Oᵃᵛᵍ decreased to a very low value, leading to increased TCP. On the other hand, the radiation damage and proliferation of the tumor increased for higher Oᵃᵛᵍ. Specially, the direct radiation damage became dominant for cell killing for higher Oᵃᵛᵍ.

Conclusion: We showed that the indirect apoptotic death of cancer cells, which was caused by the reduction of the oxygen level due to the radiation-induced vascular damage, enhanced the radiation cell kill ability by explicitly modeling the damage of blood vessels by radiation in a CA simulation.

ePosters

    Keywords

    Radiobiology, Blood Vessels, Simulation

    Taxonomy

    Not Applicable / None Entered.

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