# Project 1: Optimizing Treatment of GBM by FLASH

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $223,430

## Abstract

PROJECT SUMMARY/ABSTRACT – Project 1: Optimizing Treatment of GBM by FLASH
We are proposing the creation of a research program entitled, “Increasing the therapeutic index of brain tumor
treatment through innovative FLASH radiotherapy (FLASH-RT),” focused on translating a novel irradiation
modality rapidly into the clinic. The overall hypothesis to be tested is that radiation delivered at ultra-high dose
rates (compared to the much lower dose rates used in current clinical practice) can significantly ameliorate
normal tissue complications while maintaining acceptable if not improved tumor control. To test this hypothesis,
the program will deploy a comprehensive series of preclinical studies that will critically evaluate tumor control,
neurocognitive outcomes and resultant radiation injury to the brain following FLASH-RT and conventional dose
rate irradiation. Collectively, these studies will generate the requisite data sets required for the rapid translation
of the novel FLASH irradiation platform to the clinical setting. Preclinical studies in mice assessing orthotopic
tumor control, cognition, neuronal and vascular structure, immunomodulation, and oxygen-dependent
mechanisms of radiation injury are coupled with a clinical trial in GBM dog patients to inform the oncologists of
the potential benefits of this potentially paradigm shifting approach. The objectives of this program project will
be facilitated by the activities conducted by the Dosimetry/Physics/Modeling core and the Neurobehavioral core.
Project 1 will focus on the assessing the therapeutic index, comprising tumor control and normal brain injury, of
FLASH-RT compared to conventional dose rate irradiation. Orthotopic tumor-bearing mice will be treated with
FLASH and conventional RT under clinically relevant scenarios: single fraction and fractionated, with and without
concurrent chemotherapy, using electron and MV x-ray beams. The experiments will be conducted across our
institutions (CHUV, Stanford, and Indiana University) using our novel FLASH irradiation platforms, supported by
Cores 2 and 3. We will evaluate cellular and molecular mechanisms underlying the differential effects of FLASH
by assessing neuronal and tumor structure, and markers of inflammation/immunomodulation.
The success of this innovative program project grant is bolstered by the unparalleled breadth and depth of
our multi-disciplinary investigative team at UC Irvine, Stanford University, SLAC National Accelerator
Laboratory, CHUV/Lausanne University Hospital, and Indiana University that has pioneered the
development of the initial experimental infrastructure for conducting FLASH-RT research and produced strong
preclinical evidence of increased therapeutic index, comprising expertise in radiation oncology, radiobiology,
medical physics, and preclinical imaging and accelerator science.
In summary, Project 1 will pave the way for near-term clinical translation of FLASH-RT by systematically testing
FLASH and conventiona...

## Key facts

- **NIH application ID:** 10652597
- **Project number:** 5P01CA244091-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Charles Limoli
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $223,430
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10652597

## Citation

> US National Institutes of Health, RePORTER application 10652597, Project 1: Optimizing Treatment of GBM by FLASH (5P01CA244091-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10652597. Licensed CC0.

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