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Dose-Volume Effects in TCP for Hypoxic and Oxygenated Tumors

A Chvetsov*, R Stewart, M Kim, J Meyer, University of Washington, Seattle, WA

Presentations

(Sunday, 7/12/2020)   [Eastern Time (GMT-4)]

Room: AAPM ePoster Library

Purpose: Clinical studies in radiation therapy with conventional fractionation show a reduction in the tumor control probability (TCP) with an increase in the total and hypoxic tumor volumes. One of the main objectives of this article is to derive an analytical dependence of TCP on the hypoxic and total tumor volumes and use this dependence to evaluate the hypoxia-targeted dose escalation.

Methods: The TCP equation derived from the Poisson probability distribution predicts that both 1) an increase in the number of tumor clonogens and 2) an increase in the average cell surviving fraction may contribute to the loss of local control. Using this TCP equation and the Linear Quadratic (LQ) model for cell survival in a tumor model with two discrete levels of hypoxic and oxygenated cells, we derived equations for the TCP dependence on the total and hypoxic tumor volumes. The predicted trends in the local control as a function of total and hypoxic tumor volumes were evaluated for conventional treatments for head and neck cancers.

Results: Our calculations show that the TCP dependence on the total tumor volume for completely oxygenated tumors is negligible compared to the TCP reduction observed in the clinical studies. The volume dependence in TCP is defined predominantly by hypoxic volume and is negligible for oxygenated tumors. The theoretically required dose escalation should be 100% because it was estimated that OER=2 for conventional fractionation. We have shown that clinically acceptable values of TCP would require much lower hypoxia-targeted dose escalation (<50%) with the volume effects taken into account.

Conclusion: Our simulations show that, at the dose levels used in radiation therapy, the dose-volume effects are negligible for oxygenated tumors. The dose-volume effects are defined by the hypoxic volume and can reduce the dose-escalation level required to overcome radioresistance of hypoxic cells.

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