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Overcoming Hypoxia in Large Brain Metastases Via Adpative Hypofractionation A Biological Modeling Study


L Ma

L Ma1*, C Tseng2 , A Sahgal2 , (1) Department of Radiation Oncology, UCSF School of Medicine, San Francisco, CA, (2) Department of Radiation Oncology Sunnybrook Health Sciences Centre, Toronto, ON

Presentations

WE-G-FS1-7 (Wednesday, August 2, 2017) 4:30 PM - 6:00 PM Room: Four Seasons 1


Purpose: Hypoxia is a well-known phenomenon for large brain tumors. The goal of this study is to investigate whether novel fractionation scheme such as the adaptive hyofractionation can help overcome such an effect for hypofractionated radiosurgery of large brain metastases.

Methods: A generalized biological effective dose (gBED) model was developed via directly solving the linear-quadratic survival fraction expression, and the hypoxia within a large tumor was modeled via a hypoxia reduction factor (HRF) as proposed by Carlson et al (IJROBP, Vol 79(4) 1188, 2011). The amount of the hypoxic units was randomly distributed to examine the overall effect on the target that received highly non-uniform dose distributions for 3 to 5 hypofractionated treatments. Effects of the hypoxia on both early- and late-responding tumors (α/β ranged from 3 Gy to 20 Gy) were investigated, and specifically compared for two hypofractionated treatments: (1) conventional daily fractationation and (2) adaptive hypofractionation where interfracational interval was set to be approximately 2 weeks allowing tumor volume variation and replanning of individual treatments.

Results: Regardless α/β values, relatively small amount of hypoxia (such as 10% or less) inside the target volume exhibited little difference in composite biological effective doses between the conventional daily hypofrationated treatments and the adaptive hypofractionated treatments. However, for targets with relatively low α/β values such as 3-8 Gy and a high level of hypoxia (such as 50% or higher), adaptive hypofractionation was found to deliver significantly higher (approximately 20% to 30% ) biological effective dose over the convention treatments while lowering the normal brain dose by as much as 60% for most cases. Moreover, with increasing levels of hypoxia, such an effect also monotonically increased for these targets.

Conclusion: Adaptive hypofractionation is predicted to be significantly more advantageous in overcoming hypoxia as compared to the conventional hypofractionated radiosurgery of large brain metastases.


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