ENGS 88 Honors Thesis (AB Students)

Degree Program

A.B.

Year of Graduation

2021

Faculty Advisor

P. Jack Hoopes

Document Type

Thesis (Senior Honors)

Publication Date

Spring 6-6-2021

Abstract

FLASH ultra-high dose rate radiotherapy (RT) is one of the most rapidly growing subfields of radiation oncology today due to its potential to increase the limits of the therapeutic ratio. The FLASH effect, which includes heightened normal tissue sparing paired with iso-effective tumor cell killing, has been literature documented, in a limited manner, in rodent models, a few large animals, and one clinical patients.

A porcine-based experiment was conducted to test the effects of FLASH RT on normal tissue compared to conventional (CONV) RT. A clinical linear accelerator (LINAC) was reversibly converted to be capable of FLASH RT. A female Yucatan mini- pig was irradiated at both CONV and FLASH dose rates at four different dose levels: 0, 20, 30, and 40 Gy. Gafchromic film was used for dosimetry. To assess for radiation- induced skin reactions, two novel apps were developed in MATLAB App Designer in order to quantify previously unquantifiable data. These data included skin pigmentation metrics from RGB iPhone images as well as epithelial melanin concentration from Masson-Fontana histological stain images. To assess RT-inducted skin damage, both an H&E histological stain and Optical Coherence Tomography (OCT) were implemented for measuring epithelial thickness.

Two trends were consistent across our data. First, skin reaction in terms of pigmentation, epithelial melanin, and epithelial thickness all varied proportionally with radiation dose within FLASH and CONV RT modes. Second, FLASH elicited a stronger RT-induced response across all three metrics. However, the epithelial thinning damage, based on H&E histology, was not statistically significant.

From a regression analysis, our data suggests skin pigmentation can be linearly modelled to predict epithelial thinning as a result of FLASH and CONV RT and may serve as an important noninvasive alternative for assessing radiation-induced skin damage. The FLASH effect normal tissue sparing theory was not demonstrated by this short term single animal study however it provides excellent evidence for use in future, more comprehensive FLASH radiation studies. More research should be conducted in order to bolster the strength of the currently crude linear model which correlates skin pigmentation with RT-induced epithelial thinning.

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