# Project 1: Understanding normal tissue toxicity to identify patients most likely to benefit from proton therapy.

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $563,340

## Abstract

PROJECT 1 - PROJECT SUMMARY
A potential benefit of proton beam therapy compared to conventional therapy is expected
for many treatment sites if solely judged by the dose distribution, i.e. physical parameters.
Biological differences between protons and photons are currently only considered by
applying a constant weighting factor to proton doses, i.e. a proton relative biological
effectiveness (RBE) of 1.1. There is an urgent need for additional research to examine
whether spatial variations in dose and RBE within organs at risk can explain adverse
treatment outcomes.
The potential difference in normal tissue toxicity between proton and photon irradiation
can only be assessed with studies with a substantial amount of clinical data because the
frequencies of most overt toxicities in radiation therapy is low, thus causing variations to
be typically within the noise of patient specific radiosensitivity. There is a significant
amount of clinical data available at our two institutions and equally as important, expertise
in assessment of toxicities based on blood, imaging and dosimetric biomarkers.
We hypothesize that there are fundamental differences in normal tissue toxicities between
proton and photon radiation due not only to differences in the distribution of dose but also
variations in RBE for normal tissue toxicities, which are currently poorly understood. We
aim to 1) understand the differences in normal tissue toxicities between protons and
photons by assessing dose response relationships, 2) identify biomarkers to inform
relative normal tissue complication probabilities to replace simple RBE concepts, and 3)
advance precision medicine concepts to proton radiotherapy by identifying patients that
will benefit.
Ultimately our approach will lead to novel outcome modeling concepts applicable to both
proton and photon therapy.

## Key facts

- **NIH application ID:** 10491847
- **Project number:** 5P01CA261669-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** HARALD PAGANETTI
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $563,340
- **Award type:** 5
- **Project period:** 2021-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491847

## Citation

> US National Institutes of Health, RePORTER application 10491847, Project 1: Understanding normal tissue toxicity to identify patients most likely to benefit from proton therapy. (5P01CA261669-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10491847. Licensed CC0.

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