# Research Supplements to Promote Diversity in Health-Related Research: Preclinical optimization of ultra-high dose rate (FLASH) radiotherapy parameters for translational relevance

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $88,526

## Abstract

Project Summary
Radiation therapy delivered at ultra-high dose rates may be becoming a breakthrough treatment option for cancer
patients. Targeting cancers with ultra-high radiation dose rates produces a FLASH effect, wherein control of
tumor growth is maintained similarly to conventional (CONV) radiation dose rates, but normal tissue toxicity is
significantly reduced. Although FLASH irradiation has been shown to evoke strong, reproducible responses
across many different organ systems (e.g., brain, lungs, gastrointestinal [GI] tract, skin) across multiple species,
some studies have shown that ultra-high-dose rate irradiation to have either no effect or detrimental effects on
normal tissue. This discrepancy is not clear; however, it likely stems from inconsistency in the physical radiation
beam and fractionation parameters. Furthermore, although previous studies have shown either no change in or
improved tumor responses from FLASH irradiation as compared with CONV dose rate irradiation, no studies
have looked beyond simple tumor growth delay when evaluating tumor responses. A more relevant analysis for
preclinical tumor responses to radiotherapy is the Tumor Control (TCD50) assay, and to date, no comparisons
between FLASH and CONV dose rate irradiation on the dose required to cure 50% of tumors (TCD50) have been
performed. The lack of comparisons of radiation types, the lack of consistency between physical radiation beam
parameters and fractionation, and the lack of accurate measurements of tumor control in previous FLASH
irradiation studies provides impetus to conduct this rigorous, high throughput, multi-institutional study to provide
confirmatory evidence of the reproducibility of FLASH effects. This proposed project will test the hypothesis that
there is an optimal set of physical beam parameters that will maximize the FLASH effect, and that under the
same dose parameters and the same physical dose, the FLASH effect dose response will be the same between
different radiation types. In order to test the hypothesis, Aim 1 will focus on determining whether radiation type
(e.g., electrons, photons, and photons) alters abdominal FLASH-mediated normal tissue-sparing effects, with
the expectation of similar responses to the different radiation types. In order to optimize the physical beam and
fractionation parameters to maximally reduce normal tissue toxicity, physical beam parameters (e.g., mean dose
rate, dose per pulse, pulse duration, overall delivery time, priming dose, and oxygen tension) as well as
fractionation will be systematically changed and tested (Aim 2). Aim 3 will focus on establishing the therapeutic
effects of FLASH dose rate irradiation mediate similar control of syngeneic, heterotopic tumors of three different
cancer cell lines using the more relevant TCD50 assay. The overarching goal of this project is to minimize side
effects for all cancer patients receiving radiation therapy, which will inevitably improve quality of life. Preve...

## Key facts

- **NIH application ID:** 11063601
- **Project number:** 3R01CA266673-03S1
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Emil Schueler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $88,526
- **Award type:** 3
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11063601

## Citation

> US National Institutes of Health, RePORTER application 11063601, Research Supplements to Promote Diversity in Health-Related Research: Preclinical optimization of ultra-high dose rate (FLASH) radiotherapy parameters for translational relevance (3R01CA266673-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11063601. Licensed CC0.

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