# Increasing the therapeutic index of brain tumor treatment through innovative FLASH radiotherapy

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $1,538,120

## Abstract

PROJECT SUMMARY: OVERALL
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 whether 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 across 4 projects that will evaluate effects
of FLASH-RT on tumor control and neurocognition. Work at 3 performance sites (CHUV, Stanford, Indiana) will
implement conventional and FLASH irradiation paradigms to evaluate how each radiation modality impacts GBM
tumor control, neurocognition and associated pathologies in orthotopic tumor bearing and tumor free animals
(Projects 1 and 2). A clinical trial conducted at the CHUV in Switzerland will recruit GBM dog patients to evaluate
the therapeutic benefits of dose escalation using the FLASH modality. Lastly, each performance site will be
involved in elucidating the mechanistic basis of the FLASH effect by altering oxygen tension during irradiation
and by implementing redox sensitive transgenic mouse models. Importantly, this work will be facilitated and
integrated by two critical research cores (dosimetry/physics and neurobehavioral). In the Dosimetry and Physics
Core 2, radiation dosimetry will be cross-validated and technological innovation will be implemented across all
irradiation platforms at the CHUV, Stanford and Indiana University. In the Neurobehavioral Core 3, animals
irradiated at each performance site will be shipped to UCI where animals will be subjected to a standard and
comprehensive battery of carefully controlled behavioral tests designed to evaluate how each irradiation
paradigm functionally impacts cognition. The Administrative Core will serve as the organizational hub for all
scientific and programmatic activities. The overall goal of this Core will be to centralize these activities while
promoting efficiency in operations and transparency for the program investigators.

## Key facts

- **NIH application ID:** 10652596
- **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:** $1,538,120
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10652596

## Citation

> US National Institutes of Health, RePORTER application 10652596, Increasing the therapeutic index of brain tumor treatment through innovative FLASH radiotherapy (5P01CA244091-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10652596. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*