# Flexible Tools for Pre-Clinical Studies to Answer Key Questions UnderlyingHeavy-Ion Radiotherapy

> **NIH NIH U01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $654,731

## Abstract

SUMMARY / ABSTRACT
 Heavy-ion radiation therapy (HIRT) differs from other radiotherapy modalities such as x rays and protons as
these high-LET (Linear Energy Transfer) radiations deposit energy far more densely on a microscopic scale.
There is currently strong interest in the introduction of HIRT to the U.S., largely based on the experience of
carbon-ion radiotherapy in Japan and Germany, where very encouraging survival rates have been reported for
a number of hard-to-treat cancers such as pancreas, rectum and sarcomas. For example, 2-year survival of 50
to 65% has been reported after combined carbon-ion and gemcitabine chemotherapy for locally-advanced
pancreatic cancer, remarkably encouraging at a post-treatment time when survival is dominated by distant
metastases. Thus there has been much discussion that, as well as producing local effects to the tumor, HIRT
may also be inducing long-range systemic anti-cancer effects. However, the underlying mechanisms for such
high-LET-induced long-range systemic effects are not understood and there is evidence that the classic
radiobiological phenomena underlying the efficacy of conventional x-ray radiotherapy, while still potentially
relevant for local tumor control, are not the dominant phenomena driving the potential systemic efficacy of
HIRT. Rather the data suggest different high-LET-induced mechanisms underlying radiation-induced long-
range anti-cancer effects – and what is not known is the LET dependence of these long-range effects.
 In this BRP, and leveraging from the unique technologies and skillsets at the Radiological Research
Accelerator Facility (RARAF) and the Laboratory for Functional Optical Imaging (LFOI), novel tools will be
developed to study and understand long-range radiation-induced biological effects, and particularly their
dependence on LET. The key tools will be 1) a series of mono-LET ion beams providing spatially defined 3-D
exposures, integrated with 2) SCAPE (Swept Confocally-Aligned Planar Excitation) wide-area 3D microscopy,
imaging within and outside the radiation field. In parallel, the BRP tools will be applied to address the central
hypothesis of LET dependence of long-range radiation effects. These studies will encompass increasing levels
of complexity from tumor cells through in-vitro tumor/tissue models to in-vivo tumor models.
 To develop and apply these technologies, an interdisciplinary team has been assembled of accelerator
physicists and radiobiologists from RARAF, and biomedical engineers from LFOI, enhanced through
continuous engagement with internationally recognized scientists and clinicians with experience in HIRT.
 Apart from the primary goal of optimizing HIRT efficacy, understanding the relevant LET dependencies in
HIRT will provide a pathway for determining the optimal ion / ions for its use – a key outcome that in turn will
likely determine the future worldwide usage of HIRT, in that the capital cost of HIRT is dominated by the choice
of ion or ions to...

## Key facts

- **NIH application ID:** 9908061
- **Project number:** 5U01CA236554-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** DAVID JONATHAN BRENNER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $654,731
- **Award type:** 5
- **Project period:** 2019-04-05 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908061

## Citation

> US National Institutes of Health, RePORTER application 9908061, Flexible Tools for Pre-Clinical Studies to Answer Key Questions UnderlyingHeavy-Ion Radiotherapy (5U01CA236554-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9908061. Licensed CC0.

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